WorldWideScience

Sample records for fda review stn

  1. New aquaculture drugs under FDA review

    Science.gov (United States)

    Bowker, James D.; Gaikowski, Mark P.

    2012-01-01

    Only eight active pharmaceutical ingredients available in 18 drug products have been approved by the U.S. Food and Drug Administration for use in aquaculture. The approval process can be lengthy and expensive, but several new drugs and label claims are under review. Progress has been made on approvals for Halamid (chloramine-T), Aquaflor (florfenicol) and 35% PeroxAid (hydrogen peroxide) as therapeutic drugs. Data are also being generated for AQUI-S 20E, a fish sedative.

  2. Current and future state of FDA-CMS parallel reviews.

    Science.gov (United States)

    Messner, D A; Tunis, S R

    2012-03-01

    The US Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS) recently proposed a partial alignment of their respective review processes for new medical products. The proposed "parallel review" not only offers an opportunity for some products to reach the market with Medicare coverage more quickly but may also create new incentives for product developers to conduct studies designed to address simultaneously the information needs of regulators, payers, patients, and clinicians.

  3. FDA's misplaced priorities: premarket review under the Family Smoking Prevention and Tobacco Control Act.

    Science.gov (United States)

    Jenson, Desmond; Lester, Joelle; Berman, Micah L

    2016-05-01

    Among other key objectives, the 2009 Family Smoking Prevention and Tobacco Control Act was designed to end an era of constant product manipulation by the tobacco industry that had led to more addictive and attractive products. The law requires new tobacco products to undergo premarket review by the US Food and Drug Administration (FDA) before they can be sold. To assess FDA's implementation of its premarket review authorities, we reviewed FDA actions on new product applications, publicly available data on industry applications to market new products, and related FDA guidance documents and public statements. We conclude that FDA has not implemented the premarket review process in a manner that prioritises the protection of public health. In particular, FDA has (1) prioritised the review of premarket applications that allow for the introduction of new tobacco products over the review of potentially non-compliant products that are already on the market; (2) misallocated resources by accommodating the industry's repeated submissions of deficient premarket applications and (3) weakened the premarket review process by allowing the tobacco industry to market new and modified products that have not completed the required review process. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. 2014 in review: FDA approval of new drugs.

    Science.gov (United States)

    Kinch, Michael S

    2017-04-01

    The year 2014 witnessed the approval by the US Food and Drug Administration (FDA) of 42 new molecular entities (NMEs), which is well above recent averages. These molecules targeted a range of molecular pathways and clinical indications, although the latter was skewed toward hepatitis C virus (HCV) infection and diabetes. By contrast, a single drug was approved for cardiovascular diseases and none for neurological indications (excepting sleeping disorders). Of note is a continued trend toward consolidation because the net number of biotechnology companies has reached its lowest point in over 25 years, raising questions about sustainability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

    Directory of Open Access Journals (Sweden)

    Juan Carlos Martínez-Aguayo

    2016-06-01

    Full Text Available ABSTRACT Background The United States Food and Drug Administration (FDA has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI and venlafaxine in children and adolescents. Objectives To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

  6. Drugs Cleared Through The FDA's Expedited Review Offer Greater Gains Than Drugs Approved By Conventional Process.

    Science.gov (United States)

    Chambers, James D; Thorat, Teja; Wilkinson, Colby L; Neumann, Peter J

    2017-08-01

    We investigated whether drugs approved by the Food and Drug Administration (FDA) through expedited review have offered larger health gains, compared to drugs approved through conventional review processes. We identified published estimates of additional health gains (measured in quality-adjusted life-years, or QALYs) associated with drugs approved in the period 1999-2012 through expedited (seventy-six drugs) versus conventional (fifty-nine) review processes. We found that drugs in at least one expedited review program offered greater gains than drugs reviewed through conventional processes (0.182 versus 0.003 QALYs). We also found that, compared to drugs not included in the same program, greater gains were provided by drugs in the priority review (0.175 versus 0.007 QALYs), accelerated approval (0.370 versus 0.031 QALYs), and fast track (0.254 versus 0.014 QALYs) programs. Our analysis suggests that the FDA has prioritized drugs that offer the largest health gains. Project HOPE—The People-to-People Health Foundation, Inc.

  7. FDA drug safety communications: a narrative review and clinical considerations for older adults.

    Science.gov (United States)

    Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

    2012-08-01

    The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

  8. Medication Exposures and Subsequent Development of Ewing Sarcoma: A Review of FDA Adverse Event Reports

    Directory of Open Access Journals (Sweden)

    Judith U. Cope

    2015-01-01

    Full Text Available Background. Ewing sarcoma family of tumors (ESFT are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT. Methods. This is a retrospective, descriptive study. A query of the FDA Adverse Event Reporting System (FAERS was conducted for all reports of ESFT, January 1, 1998, through December 31, 2013. Report narratives were individually reviewed for patient characteristics, underlying conditions and drug exposures. Results. Over 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drugs and biologics including immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies. Conclusions. This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While this study was not designed to demonstrate any clear causative association between ESFT and prior use of a single product or drug class, many drugs were used to treat immune-related disease and growth or hormonal disturbances. Further studies may be warranted to better understand possible immune or neuroendocrine abnormalities or exposure to specific classes of drugs that may predispose to the later development of ESFT.

  9. A Retrospective Review of FDA v. Brown Williamson Tobacco Corporation and the Issue of Congressional Intent

    OpenAIRE

    Brooks, Angela

    2004-01-01

    Contrary to a tradition of the FDA (Federal Food and Drug Administration) consistently maintaining that it could not assert jurisdiction over tobacco products, the agency issued a determination of jurisdiction over cigarettes and smokeless tobacco and proposed a set of regulations in 1996 in an effort to combat the public health problems caused by tobacco products. Rather than a complete ban, the FDA proposed regulations aimed solely at younger Americans due to its conclusion that such an app...

  10. Drug disposition and drug-drug interaction data in 2013 FDA new drug applications: a systematic review.

    Science.gov (United States)

    Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle

    2014-12-01

    The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  12. STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice

    Science.gov (United States)

    Williams, Nolan R.; Foote, Kelly D.; Okun, Michael S.

    2014-01-01

    When formulating a deep brain stimulation (DBS) treatment plan for a patient with Parkinson’s disease (PD), two critical questions should be addressed: 1- Which brain target should be chosen to optimize this patient’s outcome? and 2- Should this patient’s DBS operation be unilateral or bilateral? Over the past two decades, two targets have emerged as leading contenders for PD DBS; the subthalamic nucleus (STN) and the globus pallidus internus (GPi). While the GPi target does have a following, most centers have uniformly employed bilateral STN DBS for all Parkinson’s disease cases (Figure 1). This bilateral STN “one-size-fits-all” approach was challenged by an editorial entitled “STN vs. GPi: The Rematch,” which appeared in the Archives of Neurology in 2005. Since 2005, a series of well designed clinical trials and follow-up studies have addressed the question as to whether a more tailored approach to DBS therapy might improve overall outcomes. Such a tailored approach would include the options of targeting the GPi, or choosing a unilateral operation. The results of the STN vs. GPi ‘rematch’ studies support the conclusion that bilateral STN DBS may not be the best option for every Parkinson’s disease surgical patient. Off period motor symptoms and tremor improve in both targets, and with either unilateral or bilateral stimulation. Advantages of the STN target include more medication reduction, less frequent battery changes, and a more favorable economic profile. Advantages of GPi include more robust dyskinesia suppression, easier programming, and greater flexibility in adjusting medications. In cases where unilateral stimulation is anticipated, the data favor GPi DBS. This review summarizes the accumulated evidence regarding the use of bilateral vs. unilateral DBS and the selection of STN vs. GPi DBS, including definite and possible advantages of different targets and approaches. Based on this evidence, a more patient-tailored, symptom specific

  13. STN1 protects chromosome ends in Arabidopsis thaliana

    OpenAIRE

    Song, Xiangyu; Leehy, Katherine; Warrington, Ross T.; Lamb, Jonathan C.; Surovtseva, Yulia V.; Shippen, Dorothy E.

    2008-01-01

    Telomeres shield the natural ends of chromosomes from nucleolytic attack, recognition as double-strand breaks, and inappropriate processing by DNA repair machinery. The trimeric Stn1/Ten1/Cdc13 complex is critical for chromosome end protection in Saccharomyces cerevisiae, while vertebrate telomeres are protected by shelterin, a complex of six proteins that does not include STN1 or TEN1. Recent studies demonstrate that Stn1 and Ten1 orthologs in Schizosaccharomyces pombe contribute to telomere...

  14. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  15. FDA Acronyms and Abbreviations

    Data.gov (United States)

    U.S. Department of Health & Human Services — The FDA Acronyms and Abbreviations database provides a quick reference to acronyms and abbreviations related to Food and Drug Administration (FDA) activities

  16. STN1 protects chromosome ends in Arabidopsis thaliana.

    Science.gov (United States)

    Song, Xiangyu; Leehy, Katherine; Warrington, Ross T; Lamb, Jonathan C; Surovtseva, Yulia V; Shippen, Dorothy E

    2008-12-16

    Telomeres shield the natural ends of chromosomes from nucleolytic attack, recognition as double-strand breaks, and inappropriate processing by DNA repair machinery. The trimeric Stn1/Ten1/Cdc13 complex is critical for chromosome end protection in Saccharomyces cerevisiae, while vertebrate telomeres are protected by shelterin, a complex of six proteins that does not include STN1 or TEN1. Recent studies demonstrate that Stn1 and Ten1 orthologs in Schizosaccharomyces pombe contribute to telomere integrity in a complex that is distinct from the shelterin components, Pot1 and Tpp1. Thus, chromosome-end protection may be mediated by distinct subcomplexes of telomere proteins. Here we report the identification of a STN1 gene in Arabidopsis that is essential for chromosome-end protection. AtSTN1 encodes an 18-kDa protein bearing a single oligonucleotide/oligosaccharide binding fold with significant sequence similarity to the yeast Stn1 proteins. Plants null for AtSTN1 display an immediate onset of growth and developmental defects and reduced fertility. These outward phenotypes are accompanied by catastrophic loss of telomeric and subtelomeric DNA, high levels of end-to-end chromosome fusions, increased G-overhang signals, and elevated telomere recombination. Thus, AtSTN1 is a crucial component of the protective telomere cap in Arabidopsis, and likely in other multicellular eukaryotes.

  17. Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

    Science.gov (United States)

    Pradhan, Richeek; Singh, Sonal

    2018-04-11

    Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.

  18. ISLSCP II River Routing Data (STN-30p)

    Data.gov (United States)

    National Aeronautics and Space Administration — The Simulated Topological Network (STN-30p) data set provides the large-scale hydrological modeling community an accurate representation of the global river system...

  19. ISLSCP II River Routing Data (STN-30p)

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: The Simulated Topological Network (STN-30p) data set provides the large-scale hydrological modeling community an accurate representation of the global...

  20. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530)

    International Nuclear Information System (INIS)

    1984-10-01

    Supplement No. 6 to the Safety Evaluation Report for the application filed by Arizona Public Service Company, et al., for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizona, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of (1) additional information submitted by the applicant since Supplement No. 5 was issued and (2) matters that the staff had under review when Supplement No. 5 was issued

  1. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530). Supplement No. 7

    International Nuclear Information System (INIS)

    1984-12-01

    Supplement No. 7 to the Safety Evaluation Report for the application filed by Arizona Public Service Company et al. for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizona, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of: (1) additional information submitted by the applicant since Supplement No. 6 was issued; and (2) matters that the staff had under review when Supplement No. 6 was issued

  2. Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

    Directory of Open Access Journals (Sweden)

    Sarah J Moum

    Full Text Available Impulse control disorders (ICDs and dopamine dysregulation syndrome (DDS are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN and internal globus pallidus (GPi deep brain stimulation (DBS on ICD/DDS frequency and dopaminergic medication usage.A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED, and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement were examined.28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

  3. Cardiovascular Mortality of Oral Antidiabetic Drugs Approved Before and After the 2008 US FDA Guidance for Industry: A Systemic Review and Meta-Analysis.

    Science.gov (United States)

    Goyat, Rashmi; Rai, Pragya; Chang, Jongwha; Ponte, Charles D; Tan, Xi

    2018-03-21

    Both diabetes and antidiabetic drugs (ADDs) increase the risk for cardiovascular (CV) diseases. Due to the increasing concern about CV safety associated with ADDs, the US FDA revised regulatory guidelines in 2008 to include CV safety as an endpoint. The objective of the current study was to conduct a systematic review with meta-analysis to compare CV mortality of oral ADDs approved before and after the FDA's 2008 guidance. Three electronic databases (PubMed, Scopus, and the Clinical Trial Registry) were searched to retrieve studies published up to 24 February 2017. Randomized clinical trials were included in this study if they (1) were published in the English language; (2) included adults with type 2 diabetes mellitus with or without CV risk factors, who were taking at least one oral antidiabetic drug; and (3) had at least one study outcome as CV mortality. Meta-analysis was performed using a random-effects model. Small-study effects were accessed using funnel plot symmetry. The primary outcome was CV mortality. We found that there was no significant increase in CV mortality for drugs approved before and after 2008. The overall odds ratio (OR) and the upper bound of the two-sided 95% confidence interval (CI) for all drugs approved after 2008 (OR 0.74, 95% CI 0.52-1.07) were lower than the overall OR for all drugs approved before 2008 (OR 1.03, 95% CI 0.89-1.19). In addition, the upper bounds of the two-sided 95% CI for both groups of drugs before and after 2008 were below 1.3. Empagliflozin, which was approved after the guidance, was significantly associated with a reduction in CV mortality. The 2008 FDA guidance appears to have a positive impact on CV risk assessment of recently marketed drugs for the management of diabetes.

  4. FDA Drug Label Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — This file contains the data elements used for searching the FDA Online Data Repository including proprietary name, active ingredients, marketing application number...

  5. FDA Recognized Consensus Standards

    Data.gov (United States)

    U.S. Department of Health & Human Services — This database consists of those national and international standards recognized by FDA which manufacturers can declare conformity to and is part of the information...

  6. FDA Approval for Imiquimod

    Science.gov (United States)

    On July 15, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of a new indication for Aldara® (imiquimod) topical cream for the treatment of superficial basal cell carcinoma (sBCC), a type of skin cancer.

  7. EVA geen FDA

    NARCIS (Netherlands)

    Folbert, J.P.; Dagevos, J.C.

    2001-01-01

    De oprichting van een Europese Voedselautoriteit die in 2002 operationeel moet zijn. Velen zien hierin een evenbeeld van de Amerikaanse FDA (Food and Drug Administration). Deze instantie werkt echter niet zo ideaal als vaak wordt voorgesteld. Het belangrijkste verschil tussen beide instanties is de

  8. Current FDA regulatory guidance on the conduct of drug discrimination studies for NDA review: Does the scientific literature support recent recommendations?

    Science.gov (United States)

    Gauvin, David V; Zimmermann, Zachary J; Kallman, Mary Jeanne

    2016-11-01

    The Controlled Substances Staff of the Center for Drug Evaluation and Research at the US Food and Drug Administration and the Pharmaceutical Research Manufacturers Association (PhRMA) conducted a series of open forum dialog sessions between 2006 and 2016. A Cross Company Abuse Liability Council (CCALC) was formed during the process of this unique collaborative effort between Industry and Federal Regulators whose goals were to establish the development of standards for the preclinical screening of new molecular entities for schedule control actions required as part of every New Drug Application process. The draft guidance document was published and disseminated in 2010, which allowed for alternative approaches to each study protocol requirement needed for NDA review, if the approach satisfied the requirements of the applicable statutes and regulations (i.e., the controlled substance act). In a series of recent pre-study protocol reviews requested by confidential Pharmaceutical Sponsors of MPI Research, the CSS staff appeared to change its policy and set forth to require all drug discrimination study data to be generated under "extinction" test sessions. MPI Research is a Contract Research Organization acting on behalf of pharmaceutical companies and bound under separate confidentiality agreements. The purpose of this review is to highlight the data appearing in peer-reviewed scientific journals that do not support the regulatory administrative constraints on one specific testing methodology (extinction) to the exclusion of another (reinforced test sessions). This mind shift represents a restrictive administrative policy by the FDA that is not supported by the published data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530). Supplement No. 9

    International Nuclear Information System (INIS)

    1985-12-01

    Supplement No. 9 to the Safety Evaluation Report for the application filed by Arizona Public Service Company et al. for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2 and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizona, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of: (1) additional information submitted by the applicant since Supplement No. 8 was issued; and (2) matters that the staff had under review when Supplement No. 8 was issued, specifically those issues which required resolution prior to Unit 2 fuel loading and testing up to 5% of full power

  10. Safety Evaluation Report related to the operation of Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Dockets Nos. STN 50-528, STN 50-529, and STN 50-530)

    International Nuclear Information System (INIS)

    1987-03-01

    Supplement No. 11 to the Safety Evaluation Report for the application filed by Arizona Public Service Company et al. for licenses to operate the Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528/529/530), located in Maricopa County, Arizone, has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. The purpose of this supplement is to update the Safety Evaluation Report by providing an evaluation of (1) additional information submitted by the applicant since Supplement No. 10 was issued and (2) other matters requiring staff review since Supplenent No. 10 was issued, specifically those issues that required resolution before Unit 3 low-power licensing

  11. Do Studies Evaluating QT/QTc Interval Prolongation with Dietary Supplements Meet FDA Standards: A Systematic Review.

    Science.gov (United States)

    Nguyen, Tinh An; Kurian, Amy; Leong, Jessica; Patel, Umang M; Shah, Sachin A

    2017-07-04

    Dietary supplement use is continuously increasing, but the safety evaluation of these products remains partial. While dietary supplements have no mandate for assessing cardiovascular safety, all new drug entities (NDE) are required to undergo a thorough QT/corrected QT (QTc) assessment to determine their propensity to impact cardiac repolarization. Independent investigators and manufacturers of dietary supplements voluntarily initiate safety studies; however, the quality of these studies is controversial. We sought to compare studies evaluating the QT/QTc effects of dietary supplements based on the International Conference of Harmonization (ICH)-E14 recommendations for NDE. Twenty-six published dietary supplement studies assessed QT/QTc interval prolongation. Sample sizes ranged from nine subjects to 206 among the 15 crossover studies, six parallel design studies, and five observational studies. A plan to account for electrocardiogram (ECG) morphological abnormalities was included in 10 studies, and two studies reported cardiovascular adverse events. Eight studies found a significant change in QT/QTc intervals. The majority of studies included in this review contained many of the critical elements recommended by the ICH E14, which includes the U.S. Food and Drug Administration guidance document for QT/QTc interval assessment. Compared with the thorough QT (TQT) standards, studies are typically well performed but can be bolstered by some study design changes. More than 30% of the included studies showed some degree of ECG changes, suggesting the need for continued cardiovascular safety assessment of dietary supplements.

  12. Is It Really FDA Approved?

    Science.gov (United States)

    ... Preventive Controls for Animal Food rule, a new regulation mandated by the FDA Food Safety Modernization Act (FSMA), requires food companies to take ... is on the market, FDA evaluates the product’s safety through research and ... But FDA regulations require nutrition information to appear on most foods, ...

  13. A review of the progress and pitfalls of FDA policy process: Planning a pathway for pharmaceutical interventions for hearing loss development.

    Science.gov (United States)

    Hammill, Tanisha L

    2017-06-01

    The Federal Food and Drug Administration, or FDA is generally considered a powerful gatekeeper, able to deliver or withhold life-saving cures and create or destroy economic windfalls. As the decades go by, and technologies, diseases, public health demands, and politics evolve, we can identify patterns of change, action and inter-action among some of these traditional stakeholders in the FDA's policy sphere. A careful examination of this agency's colorful history can shed light on central features of the agency's policy process, which has been quite receptive to its stakeholders and adaptive to change over the decades and, in turn, show the way for development in lanes which do not fit neatly into the current paradigms offered by the agency. This paper will explore the history of FDA policy process, through examination of seminal moments in FDA history, the prominent actors and focusing events within them, and the outcomes of those events, in an attempt to illuminate a pattern of behavior or processes by which a struggling field of pharmaceutical development such as interventions for hearing loss can advance. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Development of the FDA Tobacco Credibility Scale (FDA-TCS).

    Science.gov (United States)

    Schmidt, Allison M; Ranney, Leah M; Noar, Seth M; Goldstein, Adam O

    2017-01-01

    Messages from organizations with high, compared to low, credibility may be more persuasive. Whereas the tobacco industry has long recognized the importance of credibility in promoting its messages and public image, the source credibility of key tobacco control organizations has gone largely unmeasured. To assess credibility of a key tobacco regulator, we developed a scale of the US Food and Drug Administration (FDA) tobacco-related credibility. We developed and tested 30 items reflective of the dimensions of source credibility (trust, expertise, and public interest) and FDA's tobacco regulatory roles in a sample of 1353 US adults and assessed reliability and validity. Factor analysis identified 3 dimensions of the FDA Tobacco Credibility Scale (FDA-TCS): public interest, trust, and expertise. The 3 subscales showed evidence of reliability and convergent validity; all subscales were correlated with general FDA credibility and trust in government. Those who knew that the FDA regulates tobacco scored higher on the trust and expertise subscales. The subscales were also associated with support for potential regulations, suggesting criterion-related validity. The FDA-TCS allows for an understanding of the impact of credibility on responses to the FDA's tobacco control communications and regulatory efforts.

  15. Sodium–glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes: a review of US FDA data and possible conclusions

    Directory of Open Access Journals (Sweden)

    D'Elia JA

    2017-06-01

    Full Text Available John A D’Elia,1 Alissa R Segal,1,2 George P Bayliss,3 Larry A Weinrauch1 1Kidney and Hypertension Section, Joslin Diabetes Center, Harvard Medical School, 2Department of Pharmacy Practice, MCPHS University, Boston, MA, 3Division of Kidney Diseases and Hypertension, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, USA Objective: To evaluate whether adverse event reports to the US Food and Drug Administration on incidents of ketoacidosis from use of sodium glucose cotransport inhibitors (SGLT2 inhibitors provide insight into ways this new class of drugs is being prescribed with other antihyperglycemic agents; to examine possible mechanisms to explain ketoacidosis.Design and methods: Reports of adverse events concerned to SGLT2 inhibitors, namely, empagliflozin, dapagliflozin, and canagliflozin were obtained under the Freedom of Information Act for 5 years ending in August 31, 2015. The data were evaluated for incidents of ketoacidosis by looking for keywords such as diabetic ketoacidosis, ketoacidosis, lactic acidosis, acidosis, and metabolic acidosis. Results were tabulated individually for empagliflozin (n=260 adverse event reports, dapagliflozin (n=520, and canagliflozin (n=2159. Adverse events were categorized according to age, gender, and insulin use.Results: There were 46, 144, and 450 reports of ketoacidosis concerned with the use of empagliflozin, dapagliflozin, and canagliflozin, respectively. The use of SGLT2 inhibitors was not strictly limited to patients with type 2 diabetes but was cut across categories of insulin use, including a total of 172 cases of SGLT2-related ketoacidosis in individuals above the age of 40 who were not on insulin.Conclusion: Further studies should focus to detect pleiotropic effects of SGLT2 inhibitors, particularly with other oral antihyperglycemic drugs or insulin. A review of the literature suggests that patients with type 2 diabetes with low C-peptide level may be at

  16. Status report on nuclear power - information from STN databases

    International Nuclear Information System (INIS)

    Prinz, H.

    1995-01-01

    The worldwide future of nuclear power as seen about 25 years ago is presented based on a literature search in the INIS database. The role of nuclear power today, after TMI and Chernobyl, in energy supplies and in combating the greehouse effect is evaluated by literature searches in STN databases (e.g. INIS, ETDE, COMPENDEX, CA, ULIDAT, INSPEC). An evaluation is given of the different information contents of bibliographic databases such as INIS and pure information databases such as NLDB. (orig./HP)

  17. Development of the FDA Tobacco Credibility Scale (FDA-TCS)

    Science.gov (United States)

    Schmidt, Allison M.; Ranney, Leah M.; Noar, Seth M.; Goldstein, Adam O.

    2016-01-01

    Objectives Messages from organizations with high, compared to low, credibility may be more persuasive. Whereas the tobacco industry has long recognized the importance of credibility in promoting its messages and public image, the source credibility of key tobacco control organizations has gone largely unmeasured. To assess credibility of a key tobacco regulator, we developed a scale of the US Food and Drug Administration (FDA) tobacco-related credibility. Methods We developed and tested 30 items reflective of the dimensions of source credibility (trust, expertise, and public interest) and FDA’s tobacco regulatory roles in a sample of 1353 US adults and assessed reliability and validity. Results Factor analysis identified 3 dimensions of the FDA Tobacco Credibility Scale (FDA-TCS): public interest, trust, and expertise. The 3 subscales showed evidence of reliability and convergent validity; all subscales were correlated with general FDA credibility and trust in government. Those who knew that the FDA regulates tobacco scored higher on the trust and expertise subscales. The subscales were also associated with support for potential regulations, suggesting criterion-related validity. Conclusions The FDA-TCS allows for an understanding of the impact of credibility on responses to the FDA’s tobacco control communications and regulatory efforts. PMID:28638857

  18. Vitamin D discovery outpaces FDA decision making.

    Science.gov (United States)

    Marshall, Trevor G

    2008-02-01

    The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods "reduce the risk of osteoporosis". The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease. (c) 2008 Wiley Periodicals, Inc.

  19. FDA regulation of tobacco: blessing or curse for FDA professionals?

    Science.gov (United States)

    O'Reilly, James T

    2009-01-01

    Upwards of 400,000 Americans will die that year from the effects of cigarettes, which FDA will now "regulate" very gently, with its hands tied by a slick statutory protection for the largest existing tobacco marketers. Career FDA professionals will be criticized as enablers of mega-marketers' continued sales, working at the margins, arranging the paperwork for protection of megafirms' market share, and sitting by as the deaths and addictive behaviors continue. "Join the Public Health Service, inspired by a public health mission," they were told, and yet they will be unable to do much regulating of the addictive and fatal products for which they now have titular responsibility. This essay observes that these fine FDA professionals are handed the sticky remains of a messy bargain, negotiated in a distracted Congress by expensive lawyers with clients who were potent contributors to political action committees. The only formula that is not secret about the 2009 law is the way in which industry purchased sufficient allegiance to gather the votes for its adoption. The remaining mystery is how FDA could be expected to do these tasks without losing its best and brightest professionals to other fields.

  20. STN-stimulation in Parkinson's disease restores striatal inhibition of thalamocortical projection

    DEFF Research Database (Denmark)

    Geday, Jacob; Østergaard, Karen; Johnsen, Erik

    2009-01-01

    To test the hypothesis that deep brain stimulation of the subthalamic nucleus (STN) restores the inhibitory output to the striatothalamocortical loop in Parkinson's disease, we obtained functional brain images of blood flow in 10 STN-stimulated patients with Parkinson's disease. Patients were...... in the STN and in the left nucleus lentiformis. Conversely, flow declined in the left supplementary motor area (BA 6), ventrolateral nucleus of the left thalamus, and right cerebellum. Activation of the basal ganglia and deactivation of supplementary motor area and thalamus were both correlated...... with the improvement of motor function. The result is consistent with the explanation that stimulation in resting patients raises output from the STN with activation of the inhibitory basal ganglia output nuclei and subsequent deactivation of the thalamic anteroventral and ventrolateral nuclei and the supplementary...

  1. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... the FDA published a perspective article in the New England Journal of Medicine . The FDA will continue to help with the development and licensing of new stem cell therapies where the scientific evidence supports ...

  2. FDA Peanut-Containing Product Recall

    Data.gov (United States)

    U.S. Department of Health & Human Services — The FDA Peanut-Containing Product Recall widget allows you to browse the Food and Drug Administration (FDA) database of peanut butter and peanut-containing products...

  3. Methods for surgical targeting of the STN in early stage Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    C R Camalier

    2014-03-01

    Full Text Available Patients with Parkinson’s disease experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN with surgical access. While locating STN in advanced disease patients (Hoehn-Yahr III or IV is well understood and routinely performed at many centers in the context of deep brain stimulation surgery (DBS, the ability to identify this nucleus in early stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN nucleus in fifteen patients with early Parkinson’s disease (Hoehn-Yahr II, using a combination of image guided surgery, microelectrode recordings and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates, root mean squared activity have previously been found to be lower than in later stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early stage Parkinson’s disease using traditional methods.

  4. STN7 operates in retrograde signalling through controlling redox balance in the electron transfer chain

    Directory of Open Access Journals (Sweden)

    Mikko eTikkanen

    2012-12-01

    Full Text Available Phosphorylation of the major photosynthetic light harvesting antenna proteins by STN7 kinase balances excitation between PSII and PSI. Phosphorylation of such abundant proteins is unique, differing distinctively from conventional tasks of protein kinases in phosphorylation of low abundance proteins in signalling cascades. Excitation balance between PSII and PSI is critical for redox homeostasis between the plastoquinone and plastocyanin pools and PSI electron acceptors, determining the capacity of the thylakoid membrane to produce reactive oxygen species (ROS that operate as signals relaying information between chloroplasts and other cellular compartments. STN7 has also been proposed to be a conventional signalling kinase, instigating the phosphorylation cascade required for coordinated expression of photosynthesis genes and assembly of the photosynthetic machinery. The absence of STN7 kinase, however, does not prevent plants from sensing redox imbalance and adjusting the stoichiometry of the photosynthetic machinery to restore redox homeostasis. This suggests that STN7 is not essential for signalling between the chloroplast and the nucleus. Here we discuss the evolution and functions of the STN7 and other thylakoid protein kinases and phosphatases, and the inherent difficulties in analysing signalling cascades initiated from the photosynthetic machinery. Based on our analyses of literature and publicly available expression data, we conclude that STN7 exerts it signalling effect primarily by controlling chloroplast ROS homeostasis through maintaining steady-state phosphorylation of the light-harvesting II proteins and the redox balance in the thylakoid membrane. ROS are important signalling molecules with a direct effect on the development of jasmonate, which in turn relays information out from the chloroplast. We propose that thylakoid membrane redox homeostasis, regulated by SNT7, sends cell-wide signals that reprogram the entire hormonal

  5. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    International Nuclear Information System (INIS)

    Lutfi, Zainal; Ahmad, Asmat; Usup, Gires

    2014-01-01

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation

  6. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    Energy Technology Data Exchange (ETDEWEB)

    Lutfi, Zainal; Ahmad, Asmat [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia); Usup, Gires [School of Environmental and Natural Resources Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation.

  7. Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease.

    Science.gov (United States)

    Bandini, Fabio; Primavera, Alberto; Pizzorno, Matteo; Cocito, Leonardo

    2007-08-01

    We describe two patients with Parkinson's disease (PD) who developed clinical criteria of pathological gambling addiction in the setting of increased dopamine replacement therapy (levodopa and dopamine agonist medications). The second patient showed also signs of dopamine dysregulation syndrome, with an addiction to dopaminergic medication. Neither patients responded to the standard therapy for gambling behavior, but dramatically improved after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) and early postoperative withdrawal of dopaminergic therapy. The possible therapeutic role of subthalamic nucleus deep brain stimulation (STN-DBS) on such a disabling behavior needs to be investigated prospectively.

  8. Structural and resting state functional connectivity of the subthalamic nucleus: identification of motor STN parts and the hyperdirect pathway.

    Directory of Open Access Journals (Sweden)

    Ellen J L Brunenberg

    Full Text Available Deep brain stimulation (DBS for Parkinson's disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN as part of the presurgical workup could minimize these adverse effects. In this study, we assessed the STN's connectivity to motor, associative, and limbic brain areas, based on structural and functional connectivity analysis of volunteer data. For the structural connectivity, we used streamline counts derived from HARDI fiber tracking. The resulting tracks supported the existence of the so-called "hyperdirect" pathway in humans. Furthermore, we determined the connectivity of each STN voxel with the motor cortical areas. Functional connectivity was calculated based on functional MRI, as the correlation of the signal within a given brain voxel with the signal in the STN. Also, the signal per STN voxel was explained in terms of the correlation with motor or limbic brain seed ROI areas. Both right and left STN ROIs appeared to be structurally and functionally connected to brain areas that are part of the motor, associative, and limbic circuit. Furthermore, this study enabled us to assess the level of segregation of the STN motor part, which is relevant for the planning of STN DBS procedures.

  9. Prophylaxis of acute radiation dermatitis with an innovative FDA-approved two-step skin care system in a patient with head and neck cancer undergoing a platin-based radiochemotherapy: a case report and review of the literature.

    Science.gov (United States)

    Häfner, M F; Fetzner, L; Hassel, J C; Debus, J; Potthoff, K

    2013-01-01

    Radiodermatitis is a very common side effect in cancer treatment often leading to therapy delays and diminution of the patients' health state and quality of life. Despite a wide range of supportive strategies, radiodermatitis is still a major problem necessitating further improvements in prevention and treatment. Lactokine is a milk-based protein shown to assist in the reduction of skin redness. The treatment is a unique FDA-approved skin care system (R1 and R2). In this case presentation we describe the prophylactic use of R1 and R2 in a 63-year-old, female patient with a squamous cell carcinoma of the hypopharynx undergoing a platin-based chemoradiation. The application was feasible and safe and the patient developed only a slight radiodermatitis. To our knowledge this is the first report in the literature on the prophylactic use of R1 and R2. Further evidence will be provided by a prospective, clinical trial we have launched (CREAM-1; study registration in ISRCTN Registry: ISRCTN87302591). We also review the literature to give an overview about common strategies in the management of radiodermatitis.

  10. Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

    Science.gov (United States)

    McCall, W Vaughn; Benca, Ruth M; Rosenquist, Peter B; Riley, Mary Anne; McCloud, Laryssa; Newman, Jill C; Case, Doug; Rumble, Meredith; Krystal, Andrew D

    2017-01-01

    Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

  11. Neuropsychological effects of bilateral STN stimulation in Parkinson disease - A controlled study

    NARCIS (Netherlands)

    Smeding, HMM; Koning-Haanstra, M; Schuurman, PR; Nijssen, P; van Laar, T; Schmand, B; Speelman, J.D.

    2006-01-01

    Objective: To evaluate the cognitive and behavioral effects of bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD). Methods: The authors included 103 patients; 99 patients were evaluated 6 months after surgery. A control group of 39 patients with PD was formed and

  12. Palo Verde Nuclear Generating Station, Units 1, 2, and 3 (Docket Nos. STN 50-528, STN 50-529, and STN 50-530): Final environmental statement

    International Nuclear Information System (INIS)

    1982-02-01

    The proposed action is the issuance of operating licenses to the Arizona Public Service Company (APS, applicant) for the startup and operation of PVNGS, Units 1, 2, and 3, located in Maricopa County, about 24 km (15 mi) west of Buckeye, Arizona. The information in this statement represents the second assessment of the environmental impact associated with PVNGS Units 1, 2, and 3 pursuant to the guidelines of the National Environmental Policy Act of 1969 (NEPA) and Title 10 of the Code of Federal Regulations (10 CFR) Part 51 of the Commissions's Regulations. After receiving an application in July 1974 to construct this station, the staff carried out a review of impacts that would occur during its construction and operation. That evaluation was issued as a Final Environmental Statement/emdash/Construction Phase (FES-CP). After this environmental review, a safety review, an evaluation by the Advisory Committee on Reactor Safeguards, and public hearings in Phoenix, Arizona, the US Nuclear Regulatory Commission issued Construction Permits Nos. CPPR-141, CPPR-142, and CPPR-143 for the construction of PVNGS Units 1, 2, and 3. As of September 1981, the construction of Unit 1 was about 92 percent complete, Unit 2 was 68 percent complete, and Unit 3 was 26 percent complete. 11 figs., 21 tabs

  13. FDA Approves Lutathera for Neuroendocrine Tumors

    Science.gov (United States)

    FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

  14. Structure prediction-driven genetics in Saccharomyces cerevisiae identifies an interface between the t-RPA proteins Stn1 and Ten1.

    Science.gov (United States)

    Paschini, Margherita; Mandell, Edward K; Lundblad, Victoria

    2010-05-01

    In Saccharomyces cerevisiae, Cdc13, Stn1, and Ten1 are essential for both chromosome capping and telomere length homeostasis. These three proteins have been proposed to perform their roles at chromosome termini as a telomere-dedicated t-RPA complex, on the basis of several parallels with the conventional RPA complex. In this study, we have used several approaches to test whether a predicted alpha-helix in the N-terminal domain of the S. cerevisiae Stn1 protein is required for formation of the proposed t-RPA complex, in a manner analogous to the comparable helix in Rpa2. Analysis of a panel of Rpa2-OB(Stn1) chimeras indicates that whether a chimeric protein contains the Rpa2 or Stn1 version of this alpha-helix dictates its ability to function in place of Rpa2 or Stn1, respectively. In addition, mutations introduced into a hydrophobic surface of the predicted Stn1 alpha-helix eliminated association with Ten1. Strikingly, allele-specific suppression of a stn1 mutation in this helix (stn1-L164D) by a ten1 mutation (ten1-D138Y) resulted in a restored Stn1-Ten1 interaction, supporting the identification of a Stn1-Ten1 interface. We conclude that Stn1 interacts with Ten1 through an alpha-helix, in a manner analogous to the interaction between the comparable subunits of the RPA complex.

  15. The role of the FDA in the effort against AIDS.

    Science.gov (United States)

    Young, F E

    1988-01-01

    The Food and Drug Administration has instituted several pro-active measures to expedite the review of treatments, diagnostics, and vaccines for AIDS and related conditions. In particular, the agency has established a special designation--1-AA--for a potential AIDS product which gives top priority to its review. This special expedited review process for AIDS products has provided for greater cooperation between their sponsors and FDA's reviewers. AIDS products also receive prompt consideration for orphan product status--a status providing financial incentives to the developers of treatments for certain rare and complex diseases. FDA's special procedures for AIDS drugs have resulted in several major advances in available AIDS treatments. Foremost among these was the FDA's review and approval of zidovudine (commonly known as AZT) as the first effective palliative for AIDS within 107 days--an agency record. Similarly, the agency quickly evaluated and approved ELISA and Western blot diagnostic kits for detecting the presence of HIV antibody. These test kits have made an important contribution to safeguarding the nation's blood supply. The agency has also instituted new "treatment" investigational new drug regulations to allow earlier pre-approval distribution of promising experimental treatments to patients with immediately life-threatening conditions, including persons with AIDS. Under this system and its earlier prototype, eligible AIDS patients were able to receive pre-approval treatment with zidovudine and trimetrexate (an experimental drug for the treatment of AIDS patients with Pneumocystis carinii pneumonia who have experienced severe adverse reactions using standard approved therapies). The agency has made institutional reforms to effectively streamline the review of candidate AIDS treatments and vaccines. Two new centers within the agency have been established for the processing of drug and biologics. In addition,reviewing divisions have been created within

  16. FDA Regulation of Health and Fitness Equipment

    OpenAIRE

    Moss, Nicole J.

    2000-01-01

    As new "quasi-medical" devices continue to push the bounds of the FDCA definition of a medical device and with growing popular support for using the FDA to regulate previously off-limit products such as tobacco, the FDA may very well broaden its regulatory scope into the health and fitness industry. By focusing on the specific example of the scuba industry, this paper will examine first, whether the FDA has the authority to regulate athletic equipment as medical devices. Part two will explore...

  17. Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Amarilyo, Gil; Furst, Daniel E; Woo, Jennifer M P

    2016-01-01

    BACKGROUND: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. OBJECTIVES: This study sought to determine if there are differences between the FDA assessments and journal...... reports on biologic agents developed for the treatment of rheumatoid arthritis. METHODS: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American...... College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report...

  18. How the FDA and the ADA affect development of prescription drugs for oral care.

    Science.gov (United States)

    Cooley, W E

    1992-01-01

    The patient-consumer, the health professional, and the producer are all essential in the world of prescription drugs for oral care. Also essential are the Food and Drug Administration (FDA) and the American Dental Association (ADA). The FDA is charged with reviewing new-drug applications in the United States and approving those drugs that are proved safe and effective. The FDA also controls prescription-drug advertising and promotion. The ADA applies professional standards in judging all submitted dental drugs. Those drugs accepted by ADA's Council on Dental Therapeutics may display the ADA seal in labeling and advertising. All advertising for accepted products must be cleared by the ADA. An example of a prescription drug approved by the FDA and accepted by the ADA is 0.12 percent chlorhexidine gluconate oral rinse (Peridex). This drug followed the FDA's investigational-drug (IND) regulations before final approval as a treatment for gingivitis.

  19. FDA Approves Apalutamide for Prostate Cancer

    Science.gov (United States)

    Apalutamide (Erleada) is a hormone therapy that counteracts resistance to androgen deprivation therapy. Learn more about the FDA approval of apalutamide for men with castration-resistant nonmetastatic prostate cancer in this Cancer Currents blog post.

  20. FDA Approves First Therapeutic Cancer Vaccine

    Science.gov (United States)

    Sipuleucel-T (Provenge) is a relatively nontoxic treatment option for men with hormone-resistant or castration-resistant prostate cancer. The FDA's approval of the vaccine represented the first proof of principle that immunotherapy can work in cancer.

  1. Coordinated reset stimulation in a large-scale model of the STN-GPe circuit

    Directory of Open Access Journals (Sweden)

    Martin eEbert

    2014-11-01

    Full Text Available Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g. for the treatment of Parkinson’s disease (PD, is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incor- porated a detailed numerical representation of 2·104 simulated neurons. We simulated the subthalamic nucleus (STN and the globus pallidus externus (GPe. Connections within the STN were governed by spike-timing dependent plasticity (STDP. In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological activity to strongly desynchronized (healthy activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward towards a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.

  2. MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease.

    Science.gov (United States)

    Jafari, Nickey; Pahwa, Rajesh; Nazzaro, Jules M; Arnold, Paul M; Lyons, Kelly E

    2016-01-01

    To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

  3. FDA and the Chemical Brain Drainers

    DEFF Research Database (Denmark)

    Grandjean, Philippe

    2017-01-01

    Comment to: "Anesthesia and Developing Brains — Implications of the FDA Warning." Dean B. Andropoulos, M.D., M.H.C.M., and Michael F. Greene, M.D. N Engl J Med 2017; 376:905-907......Comment to: "Anesthesia and Developing Brains — Implications of the FDA Warning." Dean B. Andropoulos, M.D., M.H.C.M., and Michael F. Greene, M.D. N Engl J Med 2017; 376:905-907...

  4. FDA actions against health economic promotions, 2002-2011.

    Science.gov (United States)

    Neumann, Peter J; Bliss, Sarah K

    2012-01-01

    To investigate Food and Drug Administration (FDA) regulatory actions against drug companies' health economic promotions from 2002 through 2011 to understand how frequently and in what circumstances the agency has considered such promotions false or misleading. We reviewed all warning letters and notices of violation ("untitled letters") issued by the FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies from January 2002 through December 2011. We analyzed letters containing a violation related to "health economic promotion," defined according to one of several categories (e.g., implied claims of cost savings due to work productivity or economic claims containing unsupported statements about effectiveness or safety). We also collected information on factors such as the indication and type of media involved and whether the letter referenced Section 114 of the Food and Drug Administration Modernization Act. Of 291 DDMAC letters sent to pharmaceutical companies during the study period, 35 (12%) cited a health economic violation. The most common type of violation cited was an implied claim of cost savings due to work productivity or functioning (found in 20 letters) and economic claims containing unsubstantiated comparative claims of effectiveness, safety, or interchangeability (7 letters). The violations covered various indications, mostly commonly psychiatric disorders (6 letters) and pain (6 letters). No DDMAC letter pertained to Food and Drug Administration Modernization Act Section 114. The FDA has cited inappropriate health economic promotions in roughly 12% of the letters issued by the DDMAC. The letters highlight drug companies' interest in promoting the value of their products and the FDA's concerns in certain cases about the lack of supporting evidence. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. 77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

    Science.gov (United States)

    2012-03-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

  6. Quality assessment of digital annotated ECG data from clinical trials by the FDA ECG Warehouse.

    Science.gov (United States)

    Sarapa, Nenad

    2007-09-01

    The FDA mandates that digital electrocardiograms (ECGs) from 'thorough' QTc trials be submitted into the ECG Warehouse in Health Level 7 extended markup language format with annotated onset and offset points of waveforms. The FDA did not disclose the exact Warehouse metrics and minimal acceptable quality standards. The author describes the Warehouse scoring algorithms and metrics used by FDA, points out ways to improve FDA review and suggests Warehouse benefits for pharmaceutical sponsors. The Warehouse ranks individual ECGs according to their score for each quality metric and produces histogram distributions with Warehouse-specific thresholds that identify ECGs of questionable quality. Automatic Warehouse algorithms assess the quality of QT annotation and duration of manual QT measurement by the central ECG laboratory.

  7. FDA Expands Abiraterone Approval for Prostate Cancer

    Science.gov (United States)

    The FDA has expanded the approval of abiraterone (Zytiga) to treat men with metastatic prostate cancer. The agency approved abiraterone, in combination with prednisone, for men whose cancer that is responsive to hormone-blocking treatments (also known as castration-sensitive) and is at high risk of progressing.

  8. FDA regulations for commercial food irradiation

    International Nuclear Information System (INIS)

    Takeguchi, C.A.

    1985-01-01

    The Food and Drug Administration published an Advance Notice of Proposed Rulemaking (ANPR) on food irradiation on March 27, 1981 (FDA, 1981). The next step in the rulemaking process is a proposed rule that will deal with low-dose irradiation of certain foods and high-dose irradiation of spices. The status of the proposed regulation is discussed

  9. Distinct effects of dopamine vs STN stimulation therapies in associative learning and retention in Parkinson disease.

    Science.gov (United States)

    Ventre-Dominey, Jocelyne; Mollion, Hélène; Thobois, Stephane; Broussolle, Emmanuel

    2016-04-01

    Evidence has been provided in Parkinson's disease patients of cognitive impairments including visual memory and learning which can be partially compensated by dopamine medication or subthalamic nucleus stimulation. The effects of these two therapies can differ according to the learning processes involving the dorsal vs ventral part of the striatum. Here we aimed to investigate and compare the outcomes of dopamine vs stimulation treatment in Parkinson patient's ability to acquire and maintain over successive days their performance in visual working memory. Parkinson patients performed conditional associative learning embedded in visual (spatial and non spatial) working memory tasks over two consecutive days either ON or OFF dopaminergic drugs or STN stimulation depending on the group of patients studied. While Parkinson patients were more accurate and faster in memory tasks ON vs OFF stimulation independent of the day of testing, performance in medicated patients differed depending on the medication status during the initial task acquisition. Patients who learnt the task ON medication the first day were able to maintain or even improve their memory performance both OFF and ON medication on the second day after consolidation. These effects were observed only in patients with dopamine replacement with or without motor fluctuations. This enhancement in memory performance after having learnt under dopamine medication and not under STN stimulation was mostly significant in visuo-spatial working memory tasks suggesting that dopamine replacement in the depleted dorsal striatum is essential for retention and consolidation of learnt skill. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease?

    Science.gov (United States)

    Borden, Alaina; Wallon, David; Lefaucheur, Romain; Derrey, Stéphane; Fetter, Damien; Verin, Marc; Maltête, David

    2014-11-15

    An early and transient verbal fluency (VF) decline and impairment in frontal executive function, suggesting a cognitive microlesion effect may influence the cognitive repercussions related to subthalamic nucleus deep brain stimulation (STN-DBS). Neuropsychological tests including semantic and phonemic verbal fluency were administered both before surgery (baseline), the third day after surgery (T3), at six months (T180), and at an endpoint multiple years after surgery (Tyears). Twenty-four patients (mean age, 63.5 ± 9.5 years; mean disease duration, 12 ± 5.8 years) were included. Both semantic and phonemic VF decreased significantly in the acute post-operative period (44.4 ± 28.2% and 34.3 ± 33.4%, respectively) and remained low at 6 months compared to pre-operative levels (decrease of 3.4 ± 47.8% and 10.8 ± 32.1%) (P < 0.05). Regression analysis showed phonemic VF to be an independent factor of decreased phonemic VF at six months. Age was the only independent predictive factor for incident Parkinson's disease dementia (PDD) (F (4,19)=3.4, P<0.03). An acute post-operative decline in phonemic VF can be predictive of a long-term phonemic VF deficit. The severity of this cognitive lesion effect does not predict the development of dementia which appears to be disease-related. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Access to Investigational Drugs: FDA Expanded Access Programs or “Right‐to‐Try” Legislation?

    Science.gov (United States)

    Berglund, Jelena P.; Weatherwax, Kevin; Gerber, David E.; Adamo, Joan E.

    2015-01-01

    Abstract Purpose The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. Methods FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. Results The FDA EA program includes Single Patient‐Investigational New Drug (SP‐IND), Emergency SP‐IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. “Right‐to‐Try” legislation bypasses some of these steps, but provides no regulatory or safety oversight. Conclusion The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP‐IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. PMID:25588691

  12. Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try" Legislation?

    Science.gov (United States)

    Holbein, M E Blair; Berglund, Jelena P; Weatherwax, Kevin; Gerber, David E; Adamo, Joan E

    2015-10-01

    The Food and Drug Administration Expanded Access (EA) program and "Right-to-Try" legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. The FDA EA program includes Single Patient-Investigational New Drug (SP-IND), Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. "Right-to-Try" legislation bypasses some of these steps, but provides no regulatory or safety oversight. The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP-IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. © 2015 Wiley Periodicals, Inc.

  13. Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

    Science.gov (United States)

    Hemmerich, Natalie; Klein, Elizabeth G; Berman, Micah

    2017-08-01

    Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation. Copyright © 2017 by Duke University Press.

  14. Evaluating eating behavior treatments by FDA standards

    Directory of Open Access Journals (Sweden)

    A. Janet eTomiyama

    2014-01-01

    Full Text Available Behavioral treatments for obesity are not evaluated by the same criteria as pharmaceutical drugs, even though treatments such as low-calorie dieting are widely prescribed, require the patients’ time and investment, and may have risks. The Food and Drug Administration (FDA has a procedure for evaluating drugs, in which drugmakers must answer the following questions: (1 Is the treatment safe? (2 How dangerous is the condition the intervention is treating? (3 Is the treatment effective? (4 Is the treatment safe and effective for large numbers of people? We argue that using this framework to evaluate behavioral interventions could help identify unanswered research questions on their efficacy and effectiveness, and we use the example of low-calorie dieting to illustrate how FDA criteria might be applied in the context of behavioral medicine.

  15. Mining FDA drug labels for medical conditions.

    Science.gov (United States)

    Li, Qi; Deleger, Louise; Lingren, Todd; Zhai, Haijun; Kaiser, Megan; Stoutenborough, Laura; Jegga, Anil G; Cohen, Kevin Bretonnel; Solti, Imre

    2013-04-24

    Cincinnati Children's Hospital Medical Center (CCHMC) has built the initial Natural Language Processing (NLP) component to extract medications with their corresponding medical conditions (Indications, Contraindications, Overdosage, and Adverse Reactions) as triples of medication-related information ([(1) drug name]-[(2) medical condition]-[(3) LOINC section header]) for an intelligent database system, in order to improve patient safety and the quality of health care. The Food and Drug Administration's (FDA) drug labels are used to demonstrate the feasibility of building the triples as an intelligent database system task. This paper discusses a hybrid NLP system, called AutoMCExtractor, to collect medical conditions (including disease/disorder and sign/symptom) from drug labels published by the FDA. Altogether, 6,611 medical conditions in a manually-annotated gold standard were used for the system evaluation. The pre-processing step extracted the plain text from XML file and detected eight related LOINC sections (e.g. Adverse Reactions, Warnings and Precautions) for medical condition extraction. Conditional Random Fields (CRF) classifiers, trained on token, linguistic, and semantic features, were then used for medical condition extraction. Lastly, dictionary-based post-processing corrected boundary-detection errors of the CRF step. We evaluated the AutoMCExtractor on manually-annotated FDA drug labels and report the results on both token and span levels. Precision, recall, and F-measure were 0.90, 0.81, and 0.85, respectively, for the span level exact match; for the token-level evaluation, precision, recall, and F-measure were 0.92, 0.73, and 0.82, respectively. The results demonstrate that (1) medical conditions can be extracted from FDA drug labels with high performance; and (2) it is feasible to develop a framework for an intelligent database system.

  16. Gottlieb, the FDA and dumbing down medicine

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2017-04-01

    Full Text Available No abstract available. Article truncated at 150 words. In the last few weeks several events have occurred that might impact drug approval in the US. President Donald Trump's pick for FDA commissioner, Dr. Scott Gottlieb. Gottlieb, like many of Trump’s picks for administration healthcare positions, is a physician. He also has experience as deputy FDA commissioner from 2005-7. However, his confirmation hearing before the Senate Committee on Health, Education, Labor and Pensions alarmed some who say his deep ties to the pharmaceutical industry will cause a conflict of interest (1. Others praised Gottlieb as the right man to lead the FDA. As opposed to Trump, Gottlieb denied any connection between vaccines and autism (1,2. Dr. Gottlieb called the issue "one of the most exhaustively studied questions in medical history," before saying, "There is no plausible link between vaccines and autism. At some point, we have to accept 'no' for an answer." However, Gottlieb did not give a straight …

  17. 21 CFR 60.10 - FDA assistance on eligibility.

    Science.gov (United States)

    2010-04-01

    ... from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in... in FDA's Division of Dockets Management (HFA-305), 5630 Fishers Lane, rm. 1061, Rockville, MD 20852...

  18. FDA Adverse Event Reporting System (FAERS): Latest Quartely Data Files

    Data.gov (United States)

    U.S. Department of Health & Human Services — The FDA Adverse Event Reporting System (FAERS) is a database that contains information on adverse event and medication error reports submitted to FDA. The database...

  19. Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway

    NARCIS (Netherlands)

    Brunenberg, E.J.L.; Moeskops, P.; Backes, W.H.; Pollo, C.; Cammoun, L.; Vilanova, A.; Janssen, M.L.H.; Visser-Vandewalle, V.E.R.M.; Haar Romeny, B.M. Ter; Thiran, J.-P.; Platel, B.

    2012-01-01

    Deep brain stimulation (DBS) for Parkinson's disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN) as part of the presurgical workup could minimize these adverse

  20. Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS.

    Directory of Open Access Journals (Sweden)

    Michael S Okun

    Full Text Available To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN and globus pallidus internus (GPi deep brain stimulation (DBS for Parkinson's disease (PD.There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction.A standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III, the Hamilton depression (HAM-D and anxiety rating scales (HAM-A, the Yale-Brown obsessive-compulsive rating scale (YBOCS, the Apathy Scale (AS, and the Young mania rating scale (YMRS were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed.Thirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi. There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV did not change. No between group differences were observed in the cohort of bilateral cases.There were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.

  1. FDA toxicity databases and real-time data entry

    International Nuclear Information System (INIS)

    Arvidson, Kirk B.

    2008-01-01

    Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research, Office of Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributed in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared

  2. 78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

    Science.gov (United States)

    2013-03-05

    ... tracing of foods along the supply chain from source to points of service; 6. Demonstrate the tracking and.... The report recommends that each member of the food supply chain should be required to develop..., entitled ``Pilot Projects for Improving Product Tracing along the Food Supply System.'' FDA is announcing...

  3. FDA Regulation of Clinical Applications of CRISPR-CAS Gene-Editing Technology.

    Science.gov (United States)

    Grant, Evita V

    Scientists have repurposed an adaptive immune system of single cell organisms to create a new type of gene-editing tool: CRISPR (clustered regularly interspaced short palindromic repeats)-Cas technology. Scientists in China have reported its use in the genome modification of non-viable human embryos. This has ignited a spirited debate about the moral, ethical, scientific, and social implications of human germline genome engineering. There have also been calls for regulations; however, FDA has yet to formally announce its oversight of clinical applications of CRISPR-Cas systems. This paper reviews FDA regulation of previously controversial biotechnology breakthroughs, recombinant DNA and human cloning. It then shows that FDA is well positioned to regulate CRISPR-Cas clinical applications, due to its legislative mandates, its existing regulatory frameworks for gene therapies and assisted reproductive technologies, and other considerations.

  4. An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

    Science.gov (United States)

    Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

    2015-01-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA’s authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. PMID:25550419

  5. FDA advierte sobre cardiotoxicidad de cisaprida

    Directory of Open Access Journals (Sweden)

    Carlos Bustamante Rojas

    1998-07-01

    Full Text Available La FDA y Janssen Phamaceuticals -el fabricante de cisaprida- han advertido mediante cartas a los prescriptores que el fármaco no deberá ser utilizado simultáneamente junto con macrólidos antifúngicos, algunos antidepresivos e inhibidores de las proteasas, ya que puede aparecer prolongación del intervalo QT y severos trastornos del ritmo cardiaco. Adicionalmente, el fármaco está contraindicado en los pacientes con EPOC, ICC, cáncer avanzado y en pacientes can alteraciones del equilibrio hidroelectrolítico como hipomagnesemia o hipokalemia. Igualmente, su uso debe hacerse con bastantes precauciones en los pacientes que reciben insulina y aquellos que presentan náuseas, vómito, diarrea o deshidratación.

  6. Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial.

    Science.gov (United States)

    Weintraub, Daniel; Duda, John E; Carlson, Kimberly; Luo, Ping; Sagher, Oren; Stern, Matthew; Follett, Kenneth A; Reda, Domenic; Weaver, Frances M

    2013-10-01

    The risk of suicide behaviours post-deep brain stimulation (DBS) surgery in Parkinson's disease (PD) remains controversial. We assessed if suicide ideation and behaviours are more common in PD patients (1) randomised to DBS surgery versus best medical therapy (BMT); and (2) randomised to subthalamic nucleus (STN) versus globus pallidus interna (GPi) DBS surgery. In Phase 1 of the Veterans Affairs CSP 468 study, 255 PD patients were randomised to DBS surgery (n=121) or 6 months of BMT (n=134). For Phase 2, a total of 299 patients were randomised to STN (n=147) or GPi (n=152) DBS surgery. Patients were assessed serially with the Unified Parkinson's Disease Rating Scale Part I depression item, which queries for suicide ideation; additionally, both suicide behaviour adverse event data and proxy symptoms of increased suicide risk from the Parkinson's Disease Questionnaire (PDQ-39) and the Short Form Health Survey (SF-36) were collected. In Phase 1, no suicide behaviours were reported, and new-onset suicide ideation was rare (1.9% for DBS vs 0.9% for BMT; Fisher's exact p=0.61). Proxy symptoms of relevance to suicide ideation were similar in the two groups. Rates of suicide ideation at 6 months were similar for patients randomised to STN versus GPi DBS (1.5% vs 0.7%; Fisher's exact p=0.61), but several proxy symptoms were worse in the STN group. Results from the randomised, controlled phase of a DBS surgery study in PD patients do not support a direct association between DBS surgery and an increased risk for suicide ideation and behaviours.

  7. The FDA's program for monitoring radionuclides in food

    International Nuclear Information System (INIS)

    Baratta, E.J.

    1992-01-01

    The US Food and Drug Administration (FDA) modified its food-monitoring program in 1973 to include radioactive isotopes. There was concern at this time about the possibility of food contamination by effluents from nuclear power plants, some above-ground weapons testing by nonsignatory powers, and increased use of medical and commercial radioactive materials. The FDA decided, therefore, that a radioanalytical capability must be maintained to detect any upward trend of radioactive contamination in food. This capability would also allow the FDA to respond to any incidents that might occur in order to protect the US food supply. This program is located at the FDA's Winchester Engineering and Analytical Center, Winchester, Massachusetts

  8. Changes In Growth Culture FDA Activity Under Changing Growth Conditions

    DEFF Research Database (Denmark)

    Jørgensen, Per Elberg; Eriksen, Thomas Juul; Jensen, Bjørn K.

    1992-01-01

    of the bacteria. The FDA activity/ATP ratio was calculated for different concentrations of autoclaved sludge. A faster decay rate of ATP relative to FDA hydrolysis activity was observed, thus causing changes in the ratio. Furthermore, comparison between values obtained from pure cultures and different soils......The FDA hydrolysis capacities and bacterial biomass concentrations (estimated by determination of ATP content) of growth cultures prepared from activated sludge and wastewater, were measured to find out whether the FDA activity would reflect bacterial biomass under different physiological states...

  9. The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells.

    Science.gov (United States)

    Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang

    2017-06-15

    Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang, E-mail: wchai@wsu.edu

    2017-06-15

    Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.

  11. Draft guidance for industry; exports and imports under the FDA Export Reform and Enhancement Act of 1996--FDA. Notice.

    Science.gov (United States)

    1998-06-12

    The Food and Drug Administration (FDA) is announcing the availability of a draft guidance document entitled, "FDA Draft Guidance for Industry on: Exports and Imports Under the FDA Export Reform and Enhancement Act of 1996." The draft guidance document addresses issues pertaining to the exportation of human drugs, animal drugs, biologics, food additives, and devices as well as the importation of components, parts, accessories, or other articles for incorporation or further processing into articles intended for export.

  12. Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches.

    Science.gov (United States)

    Cardot, J-M; Garcia Arieta, A; Paixao, P; Tasevska, I; Davit, B

    2016-07-01

    The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.

  13. 21 CFR 312.86 - Focused FDA regulatory research.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section 312.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency...

  14. FDA licensure of and ACIP recommendations for vaccines.

    Science.gov (United States)

    Pickering, Larry K; Orenstein, Walter A; Sun, Wellington; Baker, Carol J

    2017-09-05

    Many healthcare providers are not familiar with the Food and Drug Administration (FDA) vaccine licensure process, the Advisory Committee on Immunization Practices (ACIP) vaccine recommendation process, and how FDA vaccine licensure and ACIP recommendations are related. Vaccines for use in the United States military and civilian populations are licensed by the FDA by several potential pathways but use of licensed vaccines in the civilian population should be based on recommendations made by the ACIP. In performing these distinct activities, FDA and ACIP function under different mandates. In this article, we discuss whether the FDA licensure pathways used to approve a vaccine impacts ACIP recommendation categories for vaccines licensed from 2006 to 2016. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Changes In Growth Culture FDA Activity Under Changing Growth Conditions

    DEFF Research Database (Denmark)

    Jørgensen, Per Elberg; Eriksen, Thomas Juul; Jensen, Bjørn K.

    1992-01-01

    The FDA hydrolysis capacities and bacterial biomass concentrations (estimated by determination of ATP content) of growth cultures prepared from activated sludge and wastewater, were measured to find out whether the FDA activity would reflect bacterial biomass under different physiological states...... of the bacteria. The FDA activity/ATP ratio was calculated for different concentrations of autoclaved sludge. A faster decay rate of ATP relative to FDA hydrolysis activity was observed, thus causing changes in the ratio. Furthermore, comparison between values obtained from pure cultures and different soils...... revealed differences up to two orders of magnitude of the ratio. Based on these results it was concluded that the FDA activity should not be applied for measurements of viable biomass in environments in which different physiological conditions occur....

  16. A hierarchical structure for human behavior classification using STN local field potentials.

    Science.gov (United States)

    Golshan, Hosein M; Hebb, Adam O; Hanrahan, Sara J; Nedrud, Joshua; Mahoor, Mohammad H

    2018-01-01

    Classification of human behavior from brain signals has potential application in developing closed-loop deep brain stimulation (DBS) systems. This paper presents a human behavior classification using local field potential (LFP) signals recorded from subthalamic nuclei (STN). A hierarchical classification structure is developed to perform the behavior classification from LFP signals through a multi-level framework (coarse to fine). At each level, the time-frequency representations of all six signals from the DBS leads are combined through an MKL-based SVM classifier to classify five tasks (speech, finger movement, mouth movement, arm movement, and random segments). To lower the computational cost, we alternatively use the inter-hemispheric synchronization of the LFPs to make three pairs out of six bipolar signals. Three classifiers are separately trained at each level of the hierarchical approach, which lead to three labels. A fusion function is then developed to combine these three labels and determine the label of the corresponding trial. Using all six LFPs with the proposed hierarchical approach improves the classification performance. Moreover, the synchronization-based method reduces the computational burden considerably while the classification performance remains relatively unchanged. Our experiments on two different datasets recorded from nine subjects undergoing DBS surgery show that the proposed approaches remarkably outperform other methods for behavior classification based on LFP signals. The LFP signals acquired from STNs contain useful information for recognizing human behavior. This can be a precursor for designing the next generation of closed-loop DBS systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Extending FDA guidance to include consumer medication information (CMI) delivery on mobile devices.

    Science.gov (United States)

    Sage, Adam; Blalock, Susan J; Carpenter, Delesha

    This paper describes the current state of consumer-focused mobile health application use and the current U.S. Food and Drug Administration (FDA) guidance on the distribution of consumer medication information (CMI), and discusses recommendations and considerations for the FDA to expand CMI guidance to include CMI in mobile applications. Smartphone-based health interventions have been linked to increased medication adherence and improved health outcomes. Trends in smartphone ownership present opportunities to more effectively communicate and disseminate medication information; however, current FDA guidance for CMI does not outline how to effectively communicate CMI on a mobile platform, particularly in regards to user-centered design and information sourcing. As evidence supporting the potential effectiveness of mobile communication in health care continues to increase, CMI developers, regulating entities, and researchers should take note. Although mobile-based CMI offers an innovative mechanism to deliver medication information, caution should be exercised. Specifically, considerations for developing mobile CMI include consumers' digital literacy, user experience (e.g., usability), and the quality and accuracy of new widely used sources of information (e.g., crowd-sourced reviews and ratings). Recommended changes to FDA guidance for CMI include altering the language about scientific accuracy to address more novel methods of information gathering (e.g., anecdotal experiences and Google Consumer Surveys) and including guidance for usability testing of mobile health applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Existing FDA pathways have potential to ensure early access to, and appropriate use of, specialty drugs.

    Science.gov (United States)

    Kesselheim, Aaron S; Tan, Yongtian Tina; Darrow, Jonathan J; Avorn, Jerry

    2014-10-01

    Specialty drugs are notable among prescription drugs in that they offer the possibility of substantial clinical improvement, come with important risks of adverse events and mortality, can be complex to manufacture or administer, and are usually extremely costly. The Food and Drug Administration (FDA) plays a critical role in ensuring that patients who could benefit from specialty drugs have access to them in a timely fashion. In this article we review the different strategies that the FDA can use to approve and influence the post-approval prescribing of specialty drugs. When specialty drugs show promise in early clinical trials, the FDA can expedite the drugs' availability to patients through expanded access programs and expedited approval pathways that speed regulatory authorization. After approval, to ensure that specialty drugs are directed to the patients who are most likely to benefit from them, the FDA can limit the scope of the drugs' indications, encourage the development of companion diagnostic tests to indicate which patients should receive the drugs, or require that manufacturers subject them to Risk Evaluation and Mitigation Strategies to ensure that their use is appropriately limited to a restricted population that is aware of the drugs' risks and benefits. Implementing these existing regulatory approaches can promote timely patient access to specialty drugs while preventing expensive and potentially inappropriate overuse. Project HOPE—The People-to-People Health Foundation, Inc.

  19. Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference.

    Science.gov (United States)

    Yu, Lawrence X; Baker, Jeffrey; Berlam, Susan C; Boam, Ashley; Brandreth, E J; Buhse, Lucinda; Cosgrove, Thomas; Doleski, David; Ensor, Lynne; Famulare, Joseph; Ganapathy, Mohan; Grampp, Gustavo; Hussong, David; Iser, Robert; Johnston, Gordon; Kesisoglou, Filippos; Khan, Mansoor; Kozlowski, Steven; Lacana, Emanuela; Lee, Sau L; Miller, Stephen; Miksinski, Sarah Pope; Moore, Christine M V; Mullin, Theresa; Raju, G K; Raw, Andre; Rosencrance, Susan; Rosolowsky, Mark; Stinavage, Paul; Thomas, Hayden; Wesdyk, Russell; Windisch, Joerg; Vaithiyalingam, Sivakumar

    2015-07-01

    On September 16 and 17, 2014, the Food and Drug Administration (FDA) and Product Quality Research Institute (PQRI) inaugurated their Conference on Evolving Product Quality. The Conference is conceived as an annual forum in which scientists from regulatory agencies, industry, and academia may exchange viewpoints and work together to advance pharmaceutical quality. This Conference Summary Report highlights key topics of this conference, including (1) risk-based approaches to pharmaceutical development, manufacturing, regulatory assessment, and post-approval changes; (2) FDA-proposed quality metrics for products, facilities, and quality management systems; (3) performance-based quality assessment and clinically relevant specifications; (4) recent developments and implementation of continuous manufacturing processes, question-based review, and European Medicines Agency (EMA)-FDA pilot for Quality-by-Design (QbD) applications; and (5) breakthrough therapies, biosimilars, and international harmonization, focusing on ICH M7 and Q3D guidelines. The second FDA/PQRI conference on advancing product quality is planned for October 5-7, 2015.

  20. TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) and the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC

  1. TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

    International Nuclear Information System (INIS)

    2016-01-01

    The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) and the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC

  2. An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation.

    Science.gov (United States)

    Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

    2015-03-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA's authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Regulatory administrative databases in FDA's Center for Biologics Evaluation and Research: convergence toward a unified database.

    Science.gov (United States)

    Smith, Jeffrey K

    2013-04-01

    Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database.

  4. Real-World Evidence, Public Participation, and the FDA.

    Science.gov (United States)

    Schwartz, Jason L

    2017-11-01

    For observers of pharmaceutical regulation and the Food and Drug Administration, these are uncertain times. Events in late 2016 raised concerns that the FDA's evidentiary standards were being weakened, compromising the agency's ability to adequately perform its regulatory and public health responsibilities. Two developments most directly contributed to these fears-the approval of eteplirsen, a treatment for Duchenne muscular dystrophy, against the recommendations of both FDA staff and an advisory committee and the December 2016 signing of the 21st Century Cures Act, which encouraged greater use by the FDA of "real-world" evidence not obtained through randomized controlled trials. The arrival of the Trump administration-with its deregulatory, industry-friendly approach-has only amplified concerns over the future of the FDA. It is too early to know whether the recent developments are truly harbingers of an FDA less likely to prevent unsafe or ineffective products from reaching the market. But elements in the two events-the role of patient narratives in deliberations regarding eteplirsen and the enthusiasm for real-world evidence in the 21st Century Cures Act-raise critical issues for the future of evidence in the FDA's work. The rigorous, inclusive approach under way to consider issues related to real-world evidence provides a model for a similarly needed inquiry regarding public participation in FDA decision-making. © 2017 The Hastings Center.

  5. Reappraising contemporary theories of subcortical participation in language: proposing an interhemispheric regulatory function for the subthalamic nucleus (STN) in the mediation of high-level linguistic processes.

    Science.gov (United States)

    Whelan, Brooke-Mai; Murdoch, Bruce E; Theodoros, Deborah G; Silburn, Peter; Hall, Bruce

    2004-02-01

    Apropos the basal ganglia, the dominant striatum and globus pallidus internus (GPi) have been hypothesised to represent integral components of subcortical language circuitry. Working subcortical language theories, however, have failed thus far to consider a role for the STN in the mediation of linguistic processes, a structure recently defined as the driving force of basal ganglia output. The aim of this research was to investigate the impact of surgically induced functional inhibition of the STN upon linguistic abilities, within the context of established models of basal ganglia participation in language. Two males with surgically induced 'lesions' of the dominant and non-dominant dorsolateral STN, aimed at relieving Parkinsonian motor symptoms, served as experimental subjects. General and high-level language profiles were compiled for each subject up to 1 month prior to and 3 months following neurosurgery, within the drug-on state (i.e., when optimally medicated). Comparable post-operative alterations in linguistic performance were observed subsequent to surgically induced functional inhibition of the left and right STN. More specifically, higher proportions of reliable decline as opposed to improvement in post-operative performance were demonstrated by both subjects on complex language tasks, hypothesised to entail the interplay of cognitive-linguistic processes. The outcomes of the current research challenge unilateralised models of functional basal ganglia organisation with the proposal of a potential interhemispheric regulatory function for the STN in the mediation of high-level linguistic processes.

  6. Prediction of STN-DBS Electrode Implantation Track in Parkinson’s Disease by Using Local Field Potentials

    Directory of Open Access Journals (Sweden)

    Ilknur eTelkes

    2016-05-01

    Full Text Available Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs, owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11-32Hz and high frequency range (200-450Hz were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11-32Hz and the range of high frequency oscillations (200-450Hz provided prediction accuracies of 72% and 68% respectively. The best prediction

  7. Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy.

    Science.gov (United States)

    Pinkerton, JoAnn V; Pickar, James H

    2016-02-01

    We review the historical regulation of drug compounding, concerns about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded bioidentical hormone therapies (CBHTs), which do not have proper labeling and warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA) on compounding. US government websites were searched for documents concerning drug compounding regulation and oversight from 1938 (passage of Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including chronologies, Congressional testimony, FDA guidelines and enforcements, and reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for articles on compounded drugs, including CBHT. Congress explicitly granted the FDA limited oversight of compounded drugs in a 1997 amendment to the FDCA, but the FDA has encountered obstacles in exercising that authority. After 64 patient deaths and 750 adversely affected patients from the 2012 meningitis outbreak due to contaminated compounded steroid injections, Congress passed the DQSA, authorizing the FDA to create a voluntary registration for facilities that manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA regulations for traditional compounding. Given history and current environment, concerns remain about CBHT product regulation and their lack of safety and efficacy data. The DQSA and its reinforcement of §503A of the FDCA solidifies FDA authority to enforce FDCA provisions against compounders of CBHT. The new law may improve compliance and accreditation by the compounding industry; support state and FDA oversight; and prevent the distribution of misbranded, adulterated, or inconsistently compounded medications, and false and misleading claims, thus reducing public health risk.

  8. Dose Matters: FDA's Guidance on Children's X-rays

    Science.gov (United States)

    ... Consumer Updates Dose Matters: FDA's Guidance on Children's X-rays Share Tweet Linkedin Pin it More sharing options ... exposure during medical procedures. The level of ionizing radiation from X-ray imaging is generally very low, but can ...

  9. 75 FR 76992 - Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing...

    Science.gov (United States)

    2010-12-10

    ... CFR 14.29. FDA encourages participation from all public stakeholders in our decisionmaking processes... speak at an OPH session, logistical procedures, and disclosure of financial relationships relevant to...

  10. Biosimilars: the need, the challenge, the future: the FDA perspective.

    Science.gov (United States)

    Epstein, Michael S; Ehrenpreis, Eli D; Kulkarni, Prasad M

    2014-12-01

    This article summarizes the brief history of the biosimilars industry, the FDA's regulations and guidance for biosimilars development, and the issues and challenges facing developers and regulators in bringing biosimilars to market. Current literature, regulations, and FDA guidance documents were summarized and interpreted to define biosimilars and to present their financial and clinical implications. Some biologic agents that will lose patent protection during the next few years may be replaced with lower cost follow-on biologics. However, unlike generic drugs, biosimilars may be structurally and functionally different from the reference product they are designed to resemble. The FDA has yet to approve any agent via the abbreviated licensure pathway for biosimilars that was passed as part of the Affordable Care Act. The FDA has issued new guidance describing processes by which manufacturers may demonstrate either biosimilarity or interchangeability with an FDA-approved biologic agent, which is required for abbreviated licensure. Biosimilars approved in Europe consist of relatively small molecules; complex large-molecule biosimilars could be subjected to a rigorous and prolonged FDA approval process, which would defeat attempts to develop lower-cost versions of biologic drugs. Biosimilar development is a consequence of the financial success of biologic therapies and their eventual patent expiration. The pharmaceutical industry must now develop complex biosimilars that resemble FDA-approved biologic agents and invent analytical tools and end points to demonstrate similarity to regulatory authorities. Already in development is a new wave of "biobetter" or "biosuperior" drugs that mimic but also improve upon a biologic drug's chemistry, formulation, or delivery.

  11. Attitudes Toward FDA Regulation of Newly Deemed Tobacco Products.

    Science.gov (United States)

    Kowitt, Sarah D; Goldstein, Adam O; Schmidt, Allison M; Hall, Marissa G; Brewer, Noel T

    2017-10-01

    To examine how smokers perceive FDA oversight of e-cigarettes, hookah, and cigars. Current US smokers (N = 1,520) participating in a randomized clinical trial of pictorial cigarette pack warnings completed a survey that included questions about attitudes toward new FDA regulations covering newly deemed tobacco products (ie, regulation of e-cigarettes, nicotine gels or liquids used in e-cigarettes, hookah, and cigars). Between 47% and 56% of current smokers viewed these new FDA regulations favorably and between 17% - 24% opposed them. Favorable attitudes toward the regulations were more common among smokers with higher quit intentions (adjusted odds ratio (aOR): 1.17, 95% CI: 1.02, 1.33) and more negative beliefs about smokers (aOR: 1.18, 95% CI: 1.05, 1.33). Participants with higher education, higher income, and previous exposure to e-cigarette advertisements had higher odds of expressing positive attitudes toward the new FDA regulations (p FDA regulation of newly deemed tobacco products favorably. Local and state policy-makers and tobacco control advocates can build on this support to enact and strengthen tobacco control provisions for e-cigarettes, cigars, and hookah.

  12. Healthy public relations: the FDA's 1930s legislative campaign.

    Science.gov (United States)

    Kay, G

    2001-01-01

    In this article, I argue that the Food and Drug Administration (FDA) is an oft-overlooked government agency that acts to preserve and secure the public's health. From its early years as an agency charged with enforcement of the 1906 Pure Food and Drugs Act, the FDA not only protected the public's health but also made the public aware of its mission, using methods as diverse as displays at county fairs and at the 1933 Chicago World's Fair, radio programming, and active correspondence. The agency encouraged the public to protect itself, particularly in those arenas in which the FDA had no regulatory authority. In addition, it may have overstepped its boundaries when it actively solicited public support for a bill submitted to Congress in the early 1930s. In the dark days of the Great Depression, the FDA contended not only with limited resources and its own feelings of inadequacy in terms of what could and could not be done to protect the populace, but also with "guinea pig" books that horrified and angered many readers. By 1938, when the agency prevailed and the revisions to the 1906 Act passed Congress and were signed into law by President Franklin D. Roosevelt, the FDA had done all that a responsible public health agency should do, and more.

  13. Application value of combined measurement of serum sTn, CA242, CA19-9 and CEA in the diagnosis of gastroenterological neoplasm

    International Nuclear Information System (INIS)

    Zhang Wanzhong; Chen Zhizhou; Fan Zhenfu

    2007-01-01

    To determine the application value of four serum tumor markers sTn, CA242, CA 19-9 and CEA in the diagnosis of gastroenterological neoplasm, the serum sTn, CA242, CA19-9 and CEA in 30 normal adult controls and 60 patients with gastroenterological neoplasm were measured by IRMA. The results showed that the serum sTn, CA242, CA19-9 and CEA levels in patients with gastric carcinoma or colorectal carcinoma were much higher than those in control group (P<0.01). The serum CEA, CA19-9 and CA242 levels in patients with colorectal carcinoma were significantly higher than those in patients with gastric carcinoma (P<0.01), but the serum sTn level in the former was markedly lower (P<0.01) than that in the latter. The sensitivity of tumor marker increased with the progress of clinical stages, with a considerably higher sensitivity for stage IV compared with stage I-II (P<0.01). The combined test of four tumor markers could be more sensitive than single test in detecting gastric carcinoma and colorectal carcinoma (P<0.05). Four tumor markers are useful for diagnosing gastroenterological neoplasm, and the combined measurement of 4 tumor markers could increase the sensitivity of detecting gastric carcinoma. (authors)

  14. Natural variation in phosphorylation of photosystem II proteins in Arabidopsis thaliana: is it caused by genetic variation in the STN kinases?

    Science.gov (United States)

    Flood, Pádraic J.; Yin, Lan; Herdean, Andrei; Harbinson, Jeremy; Aarts, Mark G. M.; Spetea, Cornelia

    2014-01-01

    Reversible phosphorylation of photosystem II (PSII) proteins is an important regulatory mechanism that can protect plants from changes in ambient light intensity and quality. We hypothesized that there is natural variation in this process in Arabidopsis (Arabidopsis thaliana), and that this results from genetic variation in the STN7 and STN8 kinase genes. To test this, Arabidopsis accessions of diverse geographical origins were exposed to two light regimes, and the levels of phospho-D1 and phospho-light harvesting complex II (LHCII) proteins were quantified by western blotting with anti-phosphothreonine antibodies. Accessions were classified as having high, moderate or low phosphorylation relative to Col-0. This variation could not be explained by the abundance of the substrates in thylakoid membranes. In genotypes with atrazine-resistant forms of the D1 protein, low D1 and LHCII protein phosphorylation was observed, which may be due to low PSII efficiency, resulting in reduced activation of the STN kinases. In the remaining genotypes, phospho-D1 levels correlated with STN8 protein abundance in high-light conditions. In growth light, D1 and LHCII phosphorylation correlated with longitude and in the case of LHCII phosphorylation also with temperature variability. This suggests a possible role of natural variation in PSII protein phosphorylation in the adaptation of Arabidopsis to diverse environments. PMID:24591726

  15. 75 FR 28622 - FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of...

    Science.gov (United States)

    2010-05-21

    ...] FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U... Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U.S. Food and... relates to FDA's policies on disclosure of information to the public about FDA activities. FDA is...

  16. 76 FR 13643 - FDA Food Safety Modernization Act: Title III-A New Paradigm for Importers; Public Meeting

    Science.gov (United States)

    2011-03-14

    ... accountability for domestic and foreign food and animal feed firms in the supply chain from farm to U.S. table... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA-2011-N-0134, FDA-2011-N-0143, FDA-2011-N-0144, FDA- 2011-N-0145, and FDA-2011-N-0146] FDA Food Safety Modernization...

  17. Impact of the US FDA "Biopharmaceutics Classification System" (BCS) Guidance on Global Drug Development.

    Science.gov (United States)

    Mehta, Mehul U; Uppoor, Ramana S; Conner, Dale P; Seo, Paul; Vaidyanathan, Jayabharathi; Volpe, Donna A; Stier, Ethan; Chilukuri, Dakshina; Dorantes, Angelica; Ghosh, Tapash; Mandula, Haritha; Raines, Kimberly; Dhanormchitphong, Pariban; Woodcock, Janet; Yu, Lawrence X

    2017-12-04

    The FDA guidance on application of the biopharmaceutics classification system (BCS) for waiver of in vivo bioequivalence (BE) studies was issued in August 2000. Since then, this guidance has created worldwide interest among biopharmaceutical scientists in regulatory agencies, academia, and industry toward its implementation and further expansion. This article describes how the review implementation of this guidance was undertaken at the FDA and results of these efforts over last dozen years or so across the new, and the generic, drug domains are provided. Results show that greater than 160 applications were approved, or tentatively approved, based on the BCS approach across multiple therapeutic areas; an additional significant finding was that at least 50% of these approvals were in the central nervous system (CNS) area. These findings indicate a robust utilization of the BCS approach toward reducing unnecessary in vivo BE studies and speeding up availability of high quality pharmaceutical products. The article concludes with a look at the adoption of this framework by regulatory and health policy organizations across the globe, and FDA's current thinking on areas of improvement of this guidance.

  18. Draft environmental statement related to the proposed manufacture of floating nuclear power plants (Docket No. STN 50-437)

    International Nuclear Information System (INIS)

    1976-10-01

    The proposed action is the issuance of a manufacturing license to Offshore Power Systems for the startup and operation of a proposed manufacturing facility located at Blount Island, Jacksonville, Florida (Docket No. STN 50-436). No nuclear fuel will be handled or stored at the manufacturing site. The plants will be fueled after they have been towed to and moored within breadwaters at specific offshore locations designated by the purchaser and after an operating license has been issued by the Nuclear Regulatory Commision. Each nuclear generating plant, mounted on a floating platform, has a net capacity of 1150 MWe. This energy is provided by a pressurized water reactor steam supply system consisting of a Westinghouse four-loop 3425 MWt unit with an ice-condenser containment system. When one or more of these units is located within a single breakwater, the installation is designated an offshore power station. 3 figs., 1 tab

  19. Comparison of imaging modalities and source-localization algorithms in locating the induced activity during deep brain stimulation of the STN.

    Science.gov (United States)

    Mideksa, K G; Singh, A; Hoogenboom, N; Hellriegel, H; Krause, H; Schnitzler, A; Deuschl, G; Raethjen, J; Schmidt, G; Muthuraman, M

    2016-08-01

    One of the most commonly used therapy to treat patients with Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Identifying the most optimal target area for the placement of the DBS electrodes have become one of the intensive research area. In this study, the first aim is to investigate the capabilities of different source-analysis techniques in detecting deep sources located at the sub-cortical level and validating it using the a-priori information about the location of the source, that is, the STN. Secondly, we aim at an investigation of whether EEG or MEG is best suited in mapping the DBS-induced brain activity. To do this, simultaneous EEG and MEG measurement were used to record the DBS-induced electromagnetic potentials and fields. The boundary-element method (BEM) have been used to solve the forward problem. The position of the DBS electrodes was then estimated using the dipole (moving, rotating, and fixed MUSIC), and current-density-reconstruction (CDR) (minimum-norm and sLORETA) approaches. The source-localization results from the dipole approaches demonstrated that the fixed MUSIC algorithm best localizes deep focal sources, whereas the moving dipole detects not only the region of interest but also neighboring regions that are affected by stimulating the STN. The results from the CDR approaches validated the capability of sLORETA in detecting the STN compared to minimum-norm. Moreover, the source-localization results using the EEG modality outperformed that of the MEG by locating the DBS-induced activity in the STN.

  20. Drugs, Devices, and the FDA: Part 2

    Directory of Open Access Journals (Sweden)

    Gail A. Van Norman, MD

    2016-06-01

    Full Text Available As with new drugs, the U.S. Food and Drug Administration’s approval process is intended to provide consumers with assurance that, once it reaches the market place, a medical device is safe and effective in its intended use. Bringing a device to market takes an average of 3 to 7 years, compared with an average of 12 years for drugs. However, there are concerns that Food and Drug Administration processes may not be sufficient to meet the assurances of safety and efficacy as intended. This second part of a 2-part series reviews the basic steps in development and Food and Drug Administration approval of medical devices, and summarizes post-marketing processes for drugs and devices.

  1. Revised draft environmental statement related to construction of Atlantic Generating Station Units 1 and 2 (Docket Nos. STN 50-477 and STN 50-478)

    International Nuclear Information System (INIS)

    1976-10-01

    The proposed action is the issuance of a construction permit to Public Service Electric and Gas Company (PDE and G) for the construction of the Atlantic Generating Station (AGS), Units 1 and 2. The AGS is the first nuclear power station in the United States proposed for construction in the offshore waters on the continental shelf. The AHS will be located in the Atlantic Ocean 2.8 miles offshore of Atlantic and Ocean countries. New Jersey, 11 miles northeast of Atlantic City, and will consist of two floating nuclear power plants enclosed in a protective rubble-mound breakwater. Both plants will be identical, of standardized design, and will employ pressurized water reactors to produce up to approximately 3425 megawatts thermal (MWt) each. Steam turbine generators will use this heat to produce up to approximately 1150 megawatts of electrical power (MWe) per unit. The main condensers will be cooled by the flow of seawater drawn from within the breakwater and discharged shoreward and external to the breakwater. This statement identifies various environmental aspects and potential adverse effects associated with the construction and operation of the AGS. Based upon an approximate two-year review period which included a multidisciplined assessment of extensive survey and modeling data, these effects are considered by the staff to be of a generally acceptable nature. Breakwater construction will result in the destruction of 100 acres of benthic infauna (burrowing animals) and the development of a reef-type community on the breakwater. The production of new biomass (standing crop) by the reef community is expected to compensate for the infaunal biomass destroyed by dredging and will contribute mainly to the local sport fishery. 93 figs., 110 tabs

  2. FDA-approved small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Nielsen, Thomas E.; Clausen, Mads Hartvig

    2015-01-01

    Kinases have emerged as one of the most intensivelypursued targets in current pharmacological research,especially for cancer, due to their critical roles in cellularsignaling. To date, the US FDA has approved 28 smallmoleculekinase inhibitors, half of which were approvedin the past 3 years. While...

  3. FDA Developments: Food Code 2013 and Proposed Trans Fat Determination

    NARCIS (Netherlands)

    Grossman, M.R.

    2014-01-01

    268 Reports EFFL 4|2014 USA FDA Developments: Food Code 2013 and Proposed Trans Fat Determination Margaret Rosso Grossman* I. Food Code 2013 and Food Code Reference System Since 1993, the US Food and Drug Administration has published a Food Code, now updated every four years. In November 2013, the

  4. FDA Expands Approval of Brentuximab for Hodgkin Lymphoma

    Science.gov (United States)

    The FDA has expanded the approved uses of brentuximab (Adcetris) in people with Hodgkin lymphoma. As this Cancer Currents post explains, it can now be used in combination with three chemotherapy drugs as an initial treatment in patients with advanced disease.

  5. FDA Drug Safety Podcasts: resources for drug information.

    Science.gov (United States)

    Wu, Kimberly; Shepherd, Jennifer; Jackson, Steven; Chew, Catherine

    2013-01-01

    To describe a Web-based drug information service provided by the Food and Drug Administration (FDA) to increase the reach of Drug Safety Communications to pharmacists and other health professionals. The Division of Drug Information (DDI) within the FDA Center for Drug Evaluation and Research (CDER), Office of Communications, Silver Spring, MD, between January 2010 and April 2012. DDI provides drug information services regarding human drug products and expert advice and guidance on all aspects of CDER activities. Customers include consumers, health professionals, regulated industry, insurance companies, academia, law enforcement, and other government agencies (national and international). Use of audio podcasts to disseminate timely drug safety information targeted toward pharmacists and other health professionals. RESULTS Since 2010, DDI has recorded and published 119 FDA Drug Safety Podcasts that have reached more than 620,000 individuals. FDA Drug Safety Podcasts serve as portable and convenient options for pharmacists to stay current on the latest drug safety information. Pharmacists are encouraged to explore incorporating Web-based technologies, such as audio podcasts, into their practices.

  6. 21 CFR 5.1110 - FDA public information offices.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL...) Press Relations Staff. Press offices are located in White Oak Bldg. 1, 10903 New Hampshire Ave., Silver...

  7. Research priorities and infrastructure needs of the Family Smoking Prevention and Tobacco Control Act: science to inform FDA policy.

    Science.gov (United States)

    Leischow, Scott J; Zeller, Mitch; Backinger, Cathy L

    2012-01-01

    A new law in the United States gives the Food and Drug Administration (FDA) wide latitude to regulate tobacco products for the first time. Given the need for science to serve as a foundation for FDA actions, it is critical that a scientific review of the literature relevant to the proposed legislation be undertaken by experts in the field of nicotine and tobacco research in order to develop research priorities. This paper describes an initiative that was implemented to identify research opportunities under "The Family Smoking Prevention and Tobacco Control Act" and summarizes the conclusions and future directions derived from that initiative. Multiple research and surveillance needs were identified, such as characterization of biomarkers and increased analysis of risk perception. It was also recognized that science will play a critical role in policy determinations such as what constitutes "substantial equivalence" and that there will be considerable infrastructure needs (e.g., laboratories for product testing). Science must drive FDA's decision making regarding tobacco regulation. This article provides a summary of research opportunities identified through literature reviews related to various provisions of the new law. However, the science required by the law requires a transdisciplinary approach because of its complexity, so one of the challenges facing the FDA will be to connect the silos of research in recognition that the "system" of tobacco regulation is greater than the sum of its parts.

  8. r-CBF brain SPET before surgery and during subthalamic nuclei (STN) high frequency stimulation (DBS) in Parkinson's Disease

    International Nuclear Information System (INIS)

    Gerundini, P.; Benti, R.; De Notaris, A.; Ferrari, M.; Raimondi, A.; Mariani, C.; Antonini, A.; Pezzoli, G.; Gaini, S.M.

    2002-01-01

    Deep brain stimulation (DBS) of the subthalamic nuclei (STN) can improve motor symptoms and reduces the need for medical therapy in severe Parkinson's Disease (PD). Moreover, DBS can affect, as the medical treatment, cerebral perfusion/metabolism even in cortical/subcortical areas not primarily involved in PD motor symptoms. Aim of the study was the assessment of r-CBF changes by mean of brain SPECT in severe PD .before surgery and during DBS of the STN. Methods. 14 PD patients (duration 15.2±5.1 ys; H and Y off-score 3.6±0.7) underwent STN electrode implantation. Residual motor dysfunction was assessed by UPDRS score up to one year after surgery. SPECT was performed after i.v. injection of Tc-99m ECD (740 MBq) in PD group before and 6-9 months after surgery and in 13 age matched normals. Standardized ROIs templates were applied in brain sections to generate perfusion ratios in the cerebral cortex and basal ganglia. Statistical Parametric Mapping (SPM) analysis of SPET studies was also obtained. Results: 6 months after surgery the mean UPDRS score improvement was 48.8±26.1% (DBS on) vs pre surgery. 8 patients (R+) had UPDRS improvement >50% (mean 67.7±8.8%); 6 patients (R-) had score improvement <50% (mean 22.9±18.9%). Before surgery, motor dysfunction during therapy was similar in R+ and R- groups (mean UPDRS 19.8±8.2 vs. 21.3±9.6). During BDS, UPDRS mean score without medical therapy was lower in R+ (15.6±5.6) vs. R- (35.0±12.4; p<0.001). ROIs and SPM analysis of pre-surgery SPET studies showed significant hypoperfusion (p<0.01) in the occipital gyri of PD vs control groups. No significant differences were found by comparing pre/post surgery SPECT patterns in whole PD group. However, in R- group SPECT showed significant hypoperfusion in pre-frontal areas, parietal and occipital gyri vs R+ patients (p<0.02) and controls (p<0.01). Before surgery, R+ group had borderline occipital hypoperfusion (p=0.04) and mild increase of putaminal perfusion (p=0.03) vs

  9. Freestanding rGO-SWNT-STN Composite Film as an Anode for Li Ion Batteries with High Energy and Power Densities

    Directory of Open Access Journals (Sweden)

    Taeseup Song

    2015-12-01

    Full Text Available Freestanding Si-Ti-Ni alloy particles/reduced graphene oxide/single wall carbon nanotube composites have been prepared as an anode for lithium ion batteries via a simple filtration method. This composite electrode showed a 9% increase in reversible capacity, a two-fold higher cycle retention at 50 cycles and a two-fold higher rate capability at 2 C compared to pristine Si-Ti-Ni (STN alloy electrodes. These improvements were attributed to the suppression of the pulverization of the STN active material by the excellent mechanical properties of the reduced graphene oxide-single wall carbon nanotube networks and the enhanced kinetics associated with both electron and Li ion transport.

  10. The FDA "Deeming Rule" and Tobacco Regulatory Research.

    Science.gov (United States)

    Backinger, Cathy L; Meissner, Helen I; Ashley, David L

    2016-07-01

    In May 2016, the Food and Drug Administration extended its tobacco regulatory authorities to other products meeting the definition of a tobacco product (Deeming Rule). This authority now includes, but is not limited to, electronic nicotine delivery systems (ENDS), such as electronic cigarettes, as well as all cigars, pipes, and hookahs (waterpipes). The FDA's Center for Tobacco Products has been able to fund research projects addressing these newly deemed tobacco products through a variety of mechanisms, including partnership with the Tobacco Regulatory Science Program, National Institutes of Health. In building the evidence base to inform the regulation of and communications about new and emerging tobacco products, it is important for investigators to be mindful of the goals of tobacco regulatory science, ie, scientific inquiry specifically to inform potential regulatory decisions and actions to protect the public's health. Having solid scientific evidence will allow the FDA to make the most appropriate regulatory decisions regarding newly deemed products.

  11. Advancing women's health via FDA Critical Path Initiative.

    Science.gov (United States)

    Parekh, A; Sanhai, W; Marts, S; Uhl, K

    2007-01-01

    Studying sex and gender differences is critical to understanding diseases that affect women solely, disproportionately or differently from men. Although inclusion of both sexes is essential in clinical research, advanced technology and analysis methods offer tools to define complex biological and physicochemical differences and improve prevention, diagnosis and treatments for diseases in women and men. This paper identifies the potential for biomarker development, pharmacogenetics and bioinformatics in research under the FDA Critical Path Initiative.: � 2007 Elsevier Ltd . All rights reserved.

  12. FDA, CE mark or something else?-Thinking fast and slow.

    Science.gov (United States)

    Mishra, Sundeep

    There is a robust debate going on among the Medical Device stake-holders whether FDA is better or CE mark or something else. Currently process of obtaining an FDA approval is bogged down by ever-increasing unpredictability, inconsistency, prolonged time, and huge expense but CE mark has its own problems. Historically, the Japanese review process has tended to be the slowest among the big three but recently with the introduction of accelerated review process there has been a significant progress. While the goal of an innovator/manufacturer is to develop, manufacture and market a medical device that addresses an unmet clinical need, the requisite regulatory approval process can be very confusing. Not only there is a whole lot of jargon tossed around by regulatory affair professionals: "substantial equivalence," "PMDA," "CE mark," "Notified body," "510K" and "PMA" but the actual approval process can also be very tardy, inconsistent and expensive. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  13. FDA, CE mark or something else?—Thinking fast and slow

    Directory of Open Access Journals (Sweden)

    Sundeep Mishra

    2017-01-01

    Full Text Available There is a robust debate going on among the Medical Device stake-holders whether FDA is better or CE mark or something else. Currently process of obtaining an FDA approval is bogged down by ever-increasing unpredictability, inconsistency, prolonged time, and huge expense but CE mark has its own problems. Historically, the Japanese review process has tended to be the slowest among the big three but recently with the introduction of accelerated review process there has been a significant progress. While the goal of an innovator/manufacturer is to develop, manufacture and market a medical device that addresses an unmet clinical need, the requisite regulatory approval process can be very confusing. Not only there is a whole lot of jargon tossed around by regulatory affair professionals: “substantial equivalence,” “PMDA,” “CE mark,” “Notified body,” “510K” and “PMA” but the actual approval process can also be very tardy, inconsistent and expensive.

  14. Export of pharmaceuticals and medical devices under the federal Food, Drug & Cosmetic Act: FDA's striking change in interpretation post-Shelhigh.

    Science.gov (United States)

    Basile, Edward M; Tolomeo, Deborah; Gluck, Elizabeth

    2009-01-01

    With no communication to industry except court filings in United States v. Undetermined Quantities of Boxes of Articles of Device (Shelhigh) and a draft guidance document, the Food and Drug Administration (FDA) has articulated new policies regarding export of pharmaceutical products and medical devices. FDA's departure from its historic interpretation of the export provisions of the Federal Food, Drug, and Cosmetic Act (FDCA) significantly limits the ability of manufacturers to export misbranded drugs and medical devices that FDA deems "adulterated," contrary to the plain language and legislative intent of the FDCA. To further exacerbate the issue, FDA has begun to implement these policies without the notice-and-comment rulemaking required by the Administrative Procedures Act (APA), but rather through an enforcement proceeding brought in the United States District Court for the District of New Jersey. In a letter opinion, the District Court prevented the export of Current Good Manufacturing Practices (CGMP) --adulterated medical devices that complied with FDCA Section 801(e)(1), at least as historically interpreted by FDA. The purpose of this article is to review the history of FDA's export policies for pharmaceuticals and medical devices, particularly those aspects of the export policies that are affected by FDA's recent change in position. Three changes in FDA's interpretation of the export provisions of the FDCA will be addressed: 1) unapproved devices that a manufacturer reasonably believes are eligible for Section 510(k) clearance may no longer be exported under Section 801(e) and now must be exported under Section 802, in substantial compliance with Current CGMP; 2) adulterated devices and misbranded drugs can only be exported if the foreign purchaser's specifications cause the product to be adulterated; and 3) an article may not be exported if a like article has ever been sold or offered for sale in domestic commerce. FDA's new interpretations of FDCA

  15. The first FDA marketing authorizations of next-generation sequencing technology and tests: challenges, solutions and impact for future assays.

    Science.gov (United States)

    Bijwaard, Karen; Dickey, Jennifer S; Kelm, Kellie; Težak, Živana

    2015-01-01

    The rapid emergence and clinical translation of novel high-throughput sequencing technologies created a need to clarify the regulatory pathway for the evaluation and authorization of these unique technologies. Recently, the US FDA authorized for marketing four next generation sequencing (NGS)-based diagnostic devices which consisted of two heritable disease-specific assays, library preparation reagents and a NGS platform that are intended for human germline targeted sequencing from whole blood. These first authorizations can serve as a case study in how different types of NGS-based technology are reviewed by the FDA. In this manuscript we describe challenges associated with the evaluation of these novel technologies and provide an overview of what was reviewed. Besides making validated NGS-based devices available for in vitro diagnostic use, these first authorizations create a regulatory path for similar future instruments and assays.

  16. No sisyphean task: how the FDA can regulate electronic cigarettes.

    Science.gov (United States)

    Paradise, Jordan

    2013-01-01

    The adverse effects of smoking have fostered a natural market for smoking cessation and smoking reduction products. Smokers attempting to quit or reduce consumption have tried everything: "low" or "light" cigarettes; nicotine-infused chewing gum, lozenges, and lollipops; dermal patches; and even hypnosis. The latest craze in the quest to find a safer source of nicotine is the electronic cigarette. Electronic cigarettes (e-cigarettes) have swept the market, reaching a rapidly expanding international consumer base. Boasting nicotine delivery and the tactile feel of a traditional cigarette without the dozens of other chemical constituents that contribute to carcinogenicity, e-cigarettes are often portrayed as less risky, as a smoking reduction or even a complete smoking cessation product, and perhaps most troubling for its appeal to youth, as a flavorful, trendy, and convenient accessory. The sensationalism associated with e-cigarettes has spurred outcry from health and medical professional groups, as well as the Food and Drug Administration (FDA), because of the unknown effects on public health. Inhabiting a realm of products deemed "tobacco products" under recent 2009 legislation, e-cigarettes pose new challenges to FDA regulation because of their novel method of nicotine delivery, various mechanical and electrical parts, and nearly nonexistent safety data. Consumer use, marketing and promotional claims, and technological characteristics of e-cigarettes have also raised decades old questions of when the FDA can assert authority over products as drugs or medical devices. Recent case law restricting FDA enforcement efforts against e-cigarettes further confounds the distinction among drugs and medical devices, emerging e-cigarette products, and traditional tobacco products such as cigarettes, cigars, and smokeless tobacco. This Article investigates the e-cigarette phenomenon in the wake of the recently enacted Family Smoking Prevention and Tobacco Control Act of 2009

  17. BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements.

    Science.gov (United States)

    Davit, Barbara M; Kanfer, Isadore; Tsang, Yu Chung; Cardot, Jean-Michel

    2016-05-01

    The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies. In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing how to meet criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs. Subsequently, the World Health Organization (WHO) and European Medicines Agency (EMA) published guidelines recommending how to obtain BCS biowaivers for BCS Class III drugs (high solubility, low permeability), in addition to Class I drugs. In 2015, the US-FDA became better harmonized with the EMA and WHO following publication of two guidances for industry outlining criteria for obtaining BCS biowaivers for both Class I and Class III drugs. A detailed review and comparison of the BCS Class I and Class III criteria currently recommended by the US-FDA, EMA, and WHO revealed good convergence of the three agencies with respect to BCS biowaiver criteria. The comparison also suggested that, by applying the most conservative of the three jurisdictional approaches, it should be possible for a sponsor to design the same set of BCS biowaiver studies in preparing a submission for worldwide filing to satisfy US, European, and emerging market regulators. It is hoped that the availability of BCS Class I and Class III biowaivers in multiple jurisdictions will encourage more sponsors to request waivers of in vivo bioavailability/bioequivalence testing using the BCS approach.

  18. 76 FR 38666 - Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island...

    Science.gov (United States)

    2011-07-01

    ..., FDA must stay abreast of the latest developments in research and also communicate with stakeholders... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0012] Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island Sea Lab...

  19. The Role of the FDA and Regulatory Approval of New Devices for Diabetes Care.

    Science.gov (United States)

    Jazowski, Shelley A; Winn, Aaron N

    2017-06-01

    The Food and Drug Administration (FDA) is responsible for assuring the safety, effectiveness, and quality of medical devices in the USA. Extensive review times coupled with the demand for necessary treatments have prompted the policymakers to implement measures to speed medical devices to market.The purpose of this review is to summarize the evolution of the regulatory pathways through which medical devices utilized in diabetes care gain market access. Regulatory pathways, ranging from premarket notification to premarket approval, require distinct, yet necessary ("least burdensome") evidence demonstrating a device's safety and effectiveness. Collaboration between manufacturers, regulators, and patients has resulted in the development and approval of novel diabetes care devices, including the first hybrid closed-loop artificial pancreas. Policy provisions, ranging from the least burdensome approach to the "breakthrough device" expedited pathway, aim to balance innovation, access, and safety. Clinicians must be aware of the evolving regulatory landscape and play an active role in enhancing patient safety.

  20. Consortium on Methods Evaluating Tobacco: Research Tools to Inform FDA Regulation of Snus.

    Science.gov (United States)

    Berman, Micah L; Bickel, Warren K; Harris, Andrew C; LeSage, Mark G; O'Connor, Richard J; Stepanov, Irina; Shields, Peter G; Hatsukami, Dorothy K

    2017-10-04

    The U.S. Food and Drug Administration (FDA) has purview over tobacco products. To set policy, the FDA must rely on sound science, yet most existing tobacco research methods have not been designed to specifically inform regulation. The NCI and FDA-funded Consortium on Methods Evaluating Tobacco (COMET) was established to develop and assess valid and reliable methods for tobacco product evaluation. The goal of this paper is to describe these assessment methods using a U.S. manufactured "snus" as the test product. In designing studies that could inform FDA regulation, COMET has taken a multidisciplinary approach that includes experimental animal models and a range of human studies that examine tobacco product appeal, addictiveness, and toxicity. This paper integrates COMET's findings over the last 4 years. Consistency in results was observed across the various studies, lending validity to our methods. Studies showed low abuse liability for snus and low levels of consumer demand. Toxicity was less than cigarettes on some biomarkers but higher than medicinal nicotine. Using our study methods and the convergence of results, the snus that we tested as a potential modified risk tobacco product is likely to neither result in substantial public health harm nor benefit. This review describes methods that were used to assess the appeal, abuse liability, and toxicity of snus. These methods included animal, behavioral economics, and consumer perception studies, and clinical trials. Across these varied methods, study results showed low abuse-liability and appeal of the snus product we tested. In several studies, demand for snus was lower than for less toxic nicotine gum. The consistency and convergence of results across a range of multi-disciplinary studies lends validity to our methods and suggests that promotion of snus as a modified risk tobacco products is unlikely to produce substantial public health benefit or harm. © The Author 2017. Published by Oxford University Press

  1. Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

    Science.gov (United States)

    Halpern, Bruno; Halpern, Alfredo

    2015-02-01

    Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.

  2. Modeling and simulation in dose determination for biodefense products approved under the FDA animal rule.

    Science.gov (United States)

    Bergman, Kimberly L; Krudys, K; Seo, S K; Florian, J

    2017-04-01

    Development of effective medical countermeasures for biodefense is vital to United States biopreparedness and response in the age of terrorism, both foreign and domestic. A traditional drug development pathway toward approval is not possible for most biodefense-related indications, creating the need for alternative development pathways such as the FDA's Animal Rule. Under this unique regulatory mechanism, FDA-approval is based on adequate and well-controlled animal studies when it is neither ethical nor feasible to conduct human efficacy studies. Translation of animal efficacy findings to humans is accomplished by use of modeling and simulation techniques. Pharmacokinetic and exposure-response modeling allow effective dosing regimens in humans to be identified, which are expected to produce similar benefit to that observed in animal models of disease. In this review, the role of modeling and simulation in determining the human dose for biodefense products developed under the Food and Drug Administration's Animal Rule regulatory pathway is discussed, and case studies illustrating the utility of modeling and simulation in this area of development are presented.

  3. Public opinion about FDA regulation of menthol and nicotine.

    Science.gov (United States)

    Bolcic-Jankovic, Dragana; Biener, Lois

    2015-12-01

    Regulations that reduce nicotine and eliminate menthol in cigarettes have been proposed to the US Food and Drug Administration (FDA) as product alterations that could reduce smoking prevalence in the USA. This study sought to assess the public response to either action. A mail survey of a representative sample of 1074 adults was conducted in two major metropolitan areas to determine the level of support for immediate, gradual or no reduction of menthol and nicotine in cigarettes. There was more support for reducing nicotine (79%) than for reducing or removing menthol (59.5%). Most smokers (59.2%; 95% CI 50.7 to 67.2) and 36% of non-smokers (95% CI 31.7 to 40.8) opposed eliminating menthol, but few smokers (23.8%) or non-smokers (20.3%) were opposed to reducing nicotine. Logistic regression showed no significant effect of smoking status on support for reductions in nicotine, but that smokers were significantly less supportive than non-smokers of FDA action on menthol (OR=0.32, 95% CI 0.21 to 0.49). A significant race by smoking status interaction showed that African-American smokers were more supportive of removing menthol than non-African-American smokers. The greater smoker support for reductions in nicotine than menthol could be due to inaccurate beliefs about the disease risk associated with the two substances (ie, a belief that nicotine is more harmful than menthol), or to greater awareness of the sensory role that menthol plays in smokers' satisfaction. In any case, if FDA goes ahead with regulations to remove menthol, it will be important to develop strategies to reduce smoker resistance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Outcomes of LASIK for myopia with FDA-approved lasers.

    Science.gov (United States)

    Bailey, Melissa D; Zadnik, Karla

    2007-04-01

    To report expected outcomes of laser in situ keratomileusis (LASIK) for myopia and myopic astigmatism from existing US Food and Drug Administration (FDA) data. Data from Summaries of Safety and Effectiveness for each of the 12 lasers approved by the FDA for LASIK for myopia or myopic astigmatism between 1998 and 2004 were recorded from the FDA Web site. The Cochran-Armitage test for trend was used to determine whether improvements in outcomes occurred with laser technology changes. For all patients, there was a statistically significant trend toward improvement with improved laser technology in the proportion of patients with uncorrected visual acuity (UCVA) of 20/20 or better, UCVA of 20/40 or better, results within +/-0.50 D of intended correction, results within +/-1.00 D of the intended correction, and night vision symptoms (all P myopia, low to moderate myopia, spherical myopia, and myopic astigmatism) for visual acuity and refractive error outcomes were similar to results for analyses for all groups combined. Conversely, there was no difference across laser types in the proportion of patients who experienced dry eye symptoms or for the proportion of patients with low to moderate myopia who experienced night vision symptoms that were worse or significantly worse than before LASIK. LASIK provides excellent visual acuity and refractive error outcomes. Night vision and dryness symptoms still occur in a significant proportion of patients. Future studies should seek to determine whether additional changes in technology, patient selection criteria, or postoperative treatment could reduce or eliminate these symptoms.

  5. Integration of new technology into clinical practice after FDA approval.

    Science.gov (United States)

    Govil, Ashul; Hao, Steven C

    2016-10-01

    Development of new medical technology is a crucial part of the advancement of medicine and our ability to better treat patients and their diseases. This process of development is long and arduous and requires a significant investment of human, financial and material capital. However, technology development can be rewarded richly by its impact on patient outcomes and successful sale of the product. One of the major regulatory hurdles to technology development is the Food and Drug Administration (FDA) approval process, which is necessary before a technology can be marketed and sold in the USA. Many businesses, medical providers and consumers believe that the FDA approval process is the only hurdle prior to use of the technology in day-to-day care. In order for the technology to be adopted into clinical use, reimbursement for both the device as well as the associated work performed by physicians and medical staff must be in place. Work and coverage decisions require Current Procedural Terminology (CPT) code development and Relative Value Scale Update Committee (RUC) valuation determination. Understanding these processes is crucial to the timely availability of new technology to patients and providers. Continued and better partnerships between physicians, industry, regulatory bodies and payers will facilitate bringing technology to market sooner and ensure appropriate utilization.

  6. Automatic extraction of drug indications from FDA drug labels.

    Science.gov (United States)

    Khare, Ritu; Wei, Chih-Hsuan; Lu, Zhiyong

    2014-01-01

    Extracting computable indications, i.e. drug-disease treatment relationships, from narrative drug resources is the key for building a gold standard drug indication repository. The two steps to the extraction problem are disease named-entity recognition (NER) to identify disease mentions from a free-text description and disease classification to distinguish indications from other disease mentions in the description. While there exist many tools for disease NER, disease classification is mostly achieved through human annotations. For example, we recently resorted to human annotations to prepare a corpus, LabeledIn, capturing structured indications from the drug labels submitted to FDA by pharmaceutical companies. In this study, we present an automatic end-to-end framework to extract structured and normalized indications from FDA drug labels. In addition to automatic disease NER, a key component of our framework is a machine learning method that is trained on the LabeledIn corpus to classify the NER-computed disease mentions as "indication vs. non-indication." Through experiments with 500 drug labels, our end-to-end system delivered 86.3% F1-measure in drug indication extraction, with 17% improvement over baseline. Further analysis shows that the indication classifier delivers a performance comparable to human experts and that the remaining errors are mostly due to disease NER (more than 50%). Given its performance, we conclude that our end-to-end approach has the potential to significantly reduce human annotation costs.

  7. FDA finds emergency postcoital contraception safe and effective.

    Science.gov (United States)

    1996-07-12

    During a 1996 hearing, the US Food and Drug Administration (FDA) Reproductive Health Drugs Advisory Committee reached the unanimous conclusion that certain oral contraceptives (OCs) are safe and effective for use in an emergency postcoital regimen. Because such a regimen reduces the risk of unintended pregnancies by about 75%, widespread access to emergency contraception in the US could prevent as many as 1.7 million pregnancies and 1 million abortions each year. The six brands of OCs manufactured in the US which contain the necessary chemical compound are Ovral, Lo/Ovral, Nordette, Triphasil, Levlen, and Tri-Levlen. For Ovral, the regimen involves taking two pills within 72 hours of unprotected intercourse followed 12 hours later by another two pills. The other OCs require a dosage of four pills each time. When using Levlen and Tri-Levlen, the yellow pills are the only ones which are effective. Publication of the FDA's support should spur pharmaceutical companies to petition the agency for virtually automatic approval of this use of OCs. Drug manufacturers have failed to take this action to date because of the fear of the opposition of antiabortion groups and of product liability suits. Detailed information on various types of emergency contraception and on physicians who provide this service can be obtained from the Reproductive Health Technologies Project hotline (1-800-584-9911).

  8. FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

    Science.gov (United States)

    Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

    2018-02-01

    This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

  9. Spin in RCTs of anxiety medication with a positive primary outcome : A comparison of concerns expressed by the US FDA and in the published literature

    NARCIS (Netherlands)

    Beijers, Lian; Jeronimus, Bertus F; Turner, Erick H; de Jonge, Peter; Roest, Annelieke M

    2017-01-01

    Objectives: This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper.

  10. Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development

    DEFF Research Database (Denmark)

    Karsdal, M A; Henriksen, K; Leeming, D J

    2009-01-01

    The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples...

  11. Public Knowledge and Credibility Perceptions of the FDA as a Tobacco Regulator.

    Science.gov (United States)

    Schmidt, Allison M; Jarman, Kristen; Ranney, Leah M; Queen, Tara; Noar, Seth M; Ruel, Laura; Agans, Robert; Hannan, Anika; Goldstein, Adam O

    2017-09-26

    Since the US Food and Drug Administration (FDA) was granted regulatory authority over tobacco products in 2009, few studies have examined perceived credibility of the FDA in this role. The current study assessed knowledge and credibility of the FDA as a regulator of tobacco products. In a nationally representative survey of US adults (N=4,758), we assessed knowledge that the FDA regulates the manufacture, distribution, and marketing of cigarettes, and credibility of the FDA as a tobacco regulator. We examined demographic differences in knowledge and credibility, and associations of knowledge and trust in government with credibility perceptions. Less than half of respondents reported knowing the FDA regulates how cigarettes are sold (46.8%) and advertised (49.7%), and only 36.0% knew the FDA regulates how cigarettes are made, with few demographic differences. Respondents reported that the FDA was moderately credible in regulating tobacco. Knowledge of the FDA as a tobacco regulator and trust in government were the strongest predictors of credibility. Being of younger age, being White (compared to African American), and being male were associated with higher credibility ratings of the FDA. Much of the public still does not know that the FDA regulates tobacco products, and credibility perceptions are moderate. Greater knowledge of the FDA's regulatory role was associated with higher credibility; efforts that increase the public's understanding of the FDA's role as a tobacco regulator may positively impact views of the agency's credibility. This may in turn improve public reception to the FDA's messages and regulations. This study is the first to show nationally representative estimates of both knowledge and credibility of the FDA as a tobacco regulator. Our research shows further that knowledge of the FDA's tobacco regulatory roles is likely to be an important factor related to perceived credibility of the FDA. Increasing the public's knowledge of the FDA's roles may

  12. The FDA may not regulate tobacco products as "drugs" or as "medical devices".

    Science.gov (United States)

    Merrill, R A

    1998-04-01

    Professor Richard Merrill contends that the Federal Food, Drug, and Cosmetic Act does not grant the FDA regulatory authority over cigarettes and smokeless tobacco products. The fact that Congress did not expressly deny the FDA regulatory authority over tobacco cannot, Professor Merrill argues, be used to infer such authority. This inference is particularly inappropriate in the case of tobacco regulation, he maintains, because there is compelling evidence that Congress had no intention of delegating this authority to the FDA. He is unpersuaded that presidential approval legally sanctions the FDA's claim of authority by granting it a superficial political legitimacy. Finally, he reminds us of the FDA's own repeated denials of jurisdiction over tobacco products, and he recalls the numerous times that Congress passed legislation directed at tobacco without granting the FDA any role in its regulation. Professor Merrill's Essay, like the other pieces in this volume, was written after the United States District Court for the Middle District of North Carolina decided Coyne Beahm v. FDA, but before a three judge panel of the United States Court of Appeals for the Fourth Circuit reversed that decision in Brown & Williamson Tobacco Corp. v. FDA. In Coyne Beahm, the District Court held that the Federal Food, Drug, and Cosmetic Act authorized the FDA to regulate tobacco products, but not tobacco advertising. The Fourth Circuit rejected the District Court's jurisdictional ruling and invalidated the FDA's regulations in their entirety. The Clinton Administration has since requested an en banc rehearing before the Fourth Circuit.

  13. Safety Evaluation Report related to the operation of Wolf Creek Generating Station, Unit No. 1 (Docket No. STN 50-482). Supplement No. 6

    International Nuclear Information System (INIS)

    1985-06-01

    This report supplements the Safety Evaluation Report (SER) for the application filed by the Kansas Gas and Electric Company, as applicant and agent for the owners, for a license to operate the Wolf Creek Generating Station, Unit 1 (Docket No. STN 50-482). The facility is located in Coffey County, Kansas. This supplement provides recent information regarding resolution of the license conditions identified in the SER. Because of the favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the licensee at power levels greater than 5% without endangering the health and safety of the public

  14. Veřejné angažmá podnikatelů na místní a regionální úrovni

    Czech Academy of Sciences Publication Activity Database

    Cibulka, Pavel

    2009-01-01

    Roč. 107, č. 3 (2009), s. 702-703 ISSN 0862-6111. [Veřejné angažmá podnikatelů na místní a regionální úrovni 1800-1914. Ostrava, 05.03.2009-06.03.2009] R&D Projects: GA ČR GA409/07/1194 Institutional research plan: CEZ:AV0Z80150510 Keywords : businessmen * Central Europe * public life Subject RIV: AB - History

  15. The FDA “Deeming Rule” and Tobacco Regulatory Research

    Science.gov (United States)

    Backinger, Cathy L.; Meissner, Helen I.; Ashley, David L.

    2016-01-01

    In May 2016, the Food and Drug Administration extended its tobacco regulatory authorities to other products meeting the definition of a tobacco product (Deeming Rule). This authority now includes, but is not limited to, electronic nicotine delivery systems (ENDS), such as electronic cigarettes, as well as all cigars, pipes, and hookahs (waterpipes). The FDA’s Center for Tobacco Products has been able to fund research projects addressing these newly deemed tobacco products through a variety of mechanisms, including partnership with the Tobacco Regulatory Science Program, National Institutes of Health. In building the evidence base to inform the regulation of and communications about new and emerging tobacco products, it is important for investigators to be mindful of the goals of tobacco regulatory science, ie, scientific inquiry specifically to inform potential regulatory decisions and actions to protect the public’s health. Having solid scientific evidence will allow the FDA to make the most appropriate regulatory decisions regarding newly deemed products. PMID:29423429

  16. Repurposing FDA-approved drugs for anti-aging therapies.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Srinivasan, Bharath; Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey

    2016-11-01

    There is great interest in drugs that are capable of modulating multiple aging pathways, thereby delaying the onset and progression of aging. Effective strategies for drug development include the repurposing of existing drugs already approved by the FDA for human therapy. FDA approved drugs have known mechanisms of action and have been thoroughly screened for safety. Although there has been extensive scientific activity in repurposing drugs for disease therapy, there has been little testing of these drugs for their effects on aging. The pool of FDA approved drugs therefore represents a large reservoir of drug candidates with substantial potential for anti-aging therapy. In this paper we employ FINDSITE comb , a powerful ligand homology modeling program, to identify binding partners for proteins produced by temperature sensing genes that have been implicated in aging. This list of drugs with potential to modulate aging rates was then tested experimentally for lifespan and healthspan extension using a small invertebrate model. Three protein targets of the rotifer Brachionus manjavacas corresponding to products of the transient receptor potential gene 7, ribosomal protein S6 polypeptide 2 gene, or forkhead box C gene, were screened against a compound library consisting of DrugBank drugs including 1347 FDA approved, non-nutraceutical molecules. Twenty nine drugs ranked in the top 1 % for binding to each target were subsequently included in our experimental analysis. Continuous exposure of rotifers to 1 µM naproxen significantly extended rotifer mean lifespan by 14 %. We used three endpoints to estimate rotifer health: swimming speed (mobility proxy), reproduction (overall vitality), and mitochondria activity (cellular senescence proxy). The natural decline in swimming speed with aging was more gradual when rotifers were exposed to three drugs, so that on day 6, mean swimming speed of females was 1.19 mm/s for naproxen (P = 0.038), 1.20 for fludarabine (P = 0

  17. FDA quality assurance for radioactivity in foods and radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baratta, E.J.

    1993-01-01

    The Food and Drug Administration (FDA) has regulatory responsibility for radionuclides in foods and radiopharmaceuticals and must maintain an ongoing Quality Assurance Program. These Quality Control Programs involve the U.S. Environmental Protection Agency (EPA) and the National Institute of Standards and Technology (NIST), who supply the necessary reference materials and standards to ensure that the measurements are accurate and reproduceable. Data from EPA (1987 to 1991) and from a NIST 'Blind' Source study (1985 to 1991) show the results are accurate with an average variation from NIST values of 1.8%. The use of standard materials with the same matrices as the samples being analyzed provides credibility to the measurements. (orig.)

  18. The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

    Science.gov (United States)

    Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

    2017-05-03

    The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

  19. A clinical plan for MDMA (Ecstasy) in the treatment of posttraumatic stress disorder (PTSD): partnering with the FDA.

    Science.gov (United States)

    Doblin, Rick

    2002-01-01

    The FDA and the Spanish Ministry of Health have concluded that the risk/benefit ratio is favorable under certain circumstances for clinical studies investigating MDMA-assisted psychotherapy. Both agencies have approved pilot studies in chronic posttraumatic stress disorder (PTSD) patients who have failed to obtain relief from at least one course of conventional treatment. These studies, the only ones in the world into the therapeutic use of MDMA, are being funded by a nonprofit research and educational organization, the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org). A rationale is offered explaining why MAPS chose to focus its limited resources on MDMA, and also on PTSD patients. A Clinical Plan is elaborated for the conduct of the "adequate and well-controlled" trials necessary to evaluate the safety and efficacy of MDMA-assisted psychotherapy for PTSD, with the studies estimated to cost about 5 million dollars and to take about five years. The Clinical Plan has been developed, in part, through analysis of the studies conducted by Pfizer in its successful effort to have Zoloft approved by the FDA for use with PTSD patients, and through review of transcripts of the FDA's Psychopharmacologic Drugs Advisory Committee meeting that recommended approval of Zoloft for PTSD.

  20. Acrylamide in Food – EU versus FDA Approaches

    Directory of Open Access Journals (Sweden)

    Gabriel Mustăţea

    2015-11-01

    Full Text Available Acrylamide is a versatile organic compound that finds its way into many products in our everyday life. The presence of acrylamide in foods dates from 2002, when a series of studies published in Sweden, confirmed its presence in high temperatures processed foods. At EU level, first adopted measure was Commission Recommendation on the monitoring of acrylamide levels in food, on May 2007, extended then by Commission Recommendation 2010/307/EU. European Food Safety Authority (EFSA then, collected and compiled data, each year (2007-2010, and published an annual report. On January 2011 was adopted the Recommendation on the investigations into the levels of acrylamide in food and then, on November 2013 was adopted Commission Recommendation 2013/647/EU on investigation into levels of acrylamide in food. Based on these, EFSA had published, in June 2015 a comprehensive risk assessment on acrylamide in food. The FDA first published a draft regarding Detection and Quantitation of Acrylamide in Foods, in 2003 followed in 2004 by the Action Plan for Acrylamide in Food. In 2006 FDA published Survey Data on Acrylamide in food then in 2009, in August (updated in November a Federal Register Notice entitled: Acrylamide in food: Request for comments and for scientific data and information. Their findings have been materialized, in November 2013, into a powerful tool for industry: Draft Guidance for industry: Acrylamide in Foods. Despite research implications that exposure to acrylamide from food is safe, some consumers may choose to take measures to further reduce their acrylamide exposure. 

  1. Early Outcome of Subthalamic Nucleus Deep Brain Stimulation (STN-DBS in Advanced Parkinson Disease in First trial of Iranian Patients

    Directory of Open Access Journals (Sweden)

    Farzad Sina

    2009-11-01

    Full Text Available Background:To improve the debilitating features of Parkinson disease (PD different medical and surgical approaches are available. Subthalamic nucleus deep brain stimulation (STN-DBS was appeared to be a promising method during last two decades. This study aimed to evaluate early motor outcomes of this procedure in first trial of Iranian patients. Methods: Thirty-seven consecutive patients with advanced Parkinson disease with   poor response to common medical agents underwent bilateral STN-DBS. For assessment of motor function parameters Unified Parkinson Disease Rating scale III (UPDRS III was used. We compared total scores and subscores in three measurements performed as 1 preoperative off-medication, 2 preoperative on-medication and 3 six months postoperative on stimulation and on medication. Reduction in drug consumption was assessed with regard to administered doses of L-Dopa before and after surgery in stable states.Results: 26 men and 10 women with mean age of 50 years were evaluated (one person expired before 6-month follow-up. Mean total scores of UPDRSIII were calculated as 5.2±54.52, 2.88±18.22 and 3±12.8 in three measurements, respectively (p=0.003 .PostHoc analyses showed significant improvement among all measurements. Analysis of subscores also revealed significant amelioration in rigidity, resting tremor, hand movement, leg agility, finger tap and rapid alternating movement in on-medication phases of pre- and post-operation (all with p

  2. Impulse control and related disorders in Parkinson's disease patients treated with bilateral subthalamic nucleus stimulation: a review.

    Science.gov (United States)

    Broen, Martijn; Duits, Annelien; Visser-Vandewalle, Veerle; Temel, Yasin; Winogrodzka, Ania

    2011-07-01

    Recently, impulse control and related disorders including punding and the dopamine dysregulation syndrome (DDS) have been increasingly recognized in treated patients with Parkinson's disease (PD). Especially the impulse control disorders (ICD) such as pathological gambling, hypersexuality, compulsive eating and buying may have dramatic repercussions on family, personal and professional life. Drug replacement therapy (DRT) is believed to play an important role in the onset of these behavioral disturbances. Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) might be a therapeutic option for those patients with DRT-related behavior, it may also induce ICD. So far, little is known about the relationship between STN DBS and impulse control and related disorders. Our aim was to review the current knowledge on this relationship in PD patients. The available studies showed that stimulation of the STN is associated with both favorable and negative outcome in terms of impulse control and related disorders. Preoperative disorders may resolve or improve after STN DBS, but these can also worsen or show no change at all. Moreover, STN DBS can also reveal or even induce ICD. Possible explanations for this variability are proposed and suggestions for clinical management are given. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. 21 CFR 516.34 - FDA recognition of exclusive marketing rights.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false FDA recognition of exclusive marketing rights. 516... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive...

  4. 21 CFR 1271.27 - Will FDA assign me a registration number?

    Science.gov (United States)

    2010-04-01

    ..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA...) FDA acceptance of an establishment registration and HCT/P listing form does not constitute a determination that an establishment is in compliance with applicable rules and regulations or that the HCT/P is...

  5. OARSI-FDA initiative: defining the disease state of osteoarthritis.

    Science.gov (United States)

    Lane, N E; Brandt, K; Hawker, G; Peeva, E; Schreyer, E; Tsuji, W; Hochberg, M C

    2011-05-01

    To respond to a pre-specified set of questions posed by the United States Food and Drug Administration (FDA) on defining the disease state to inform the clinical development of drugs, biological products, and medical devices for the prevention and treatment of osteoarthritis (OA). An Osteoarthritis Research Society International (OARSI) Disease State working group was established, comprised of representatives from academia and industry. The Working Group met in person and by teleconference on several occasions from the Spring of 2008 through the Autumn of 2009 to develop consensus-based, evidence-informed responses to these questions. A report was presented at a public forum in December 2009 and accepted by the OARSI Board of Directors in the Summer of 2010. An operational definition of OA was developed incorporating current understanding of the condition. The structural changes that characterize OA at the joint level were distinguished from the patients' experience of OA as the 'disease' and 'illness', respectively. Recommendations were made regarding the evaluation of both in future OA clinical trials. The current poor understanding of the phenotypes that characterize OA was identified as an important area for future research. The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Formation of defect-free 6FDA-DAM asymmetric hollow fiber membranes for gas separations

    KAUST Repository

    Xu, Liren

    2014-06-01

    This paper reports the formation of defect-free 6FDA-DAM asymmetric hollow fiber membranes. 6FDA-polyimides are of great interest for advanced gas separation membranes, and 6FDA-DAM polyimide is a representative polymer in this family with attractive dense film properties for several potential applications. The work reported here for the 6FDA-DAM polyimide provides insight for the challenging fabrication of defect-free asymmetric hollow fiber membranes for this class of 6FDA-polyimides, which behave rather different from lower free volume polymers. Specifically, the 6FDA based materials show relatively slow phase separation rate in water quench baths, which presents a challenge for fiber spinning. For convenience, we refer to the behavior as more "non-solvent resistant" in comparison to other lower free volume polymers, since the binodal phase boundary is displaced further from the conventional position near the pure polymer-solvent axis on a ternary phase diagram in conventional polymers like Matrimid® and Ultem®. The addition of lithium nitrate to promote phase separation has a useful impact on 6FDA-DAM asymmetric hollow fiber formation. 6FDA-DAM phase diagrams using ethanol and water as non-solvent are reported, and it was found that water is less desirable as a non-solvent dope additive for defect-free fiber spinning. Phase diagrams are also reported for 6FDA-DAM dope formulation with and without the addition of lithium nitrate, and defect-free asymmetric hollow fiber membranes are reported for both cases. The effect of polymer molecular weight on defect-free fiber spinning was also investigated. Gas transport properties and morphology of hollow fibers were characterized. With several thorough case studies, this work provides a systematic guideline for defect-free fiber formation from 6FDA-polymers. © 2014 Elsevier B.V.

  7. Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

    Directory of Open Access Journals (Sweden)

    Deborah Korenstein

    Full Text Available Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA; adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing.Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14. Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1% adhered to all FDA guidelines, 41 (49.4% were non-adherent with at least one form of FDA-described bias, and 27 (32.5% were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence.Few physician-directed print pharmaceutical

  8. Safety Evaluation Report related to the operation of Wolf Creek Generating Station, Unit No. 1 (Docket No. STN 50-482). Supplement No. 5

    International Nuclear Information System (INIS)

    1985-03-01

    This report supplements the Safety Evaluation Report (SER) for the application filed by the Kansas Gas and Electric Company, as applicant and agent for the owners, for a license to operate the Wolf Creek Generating Station, Unit 1 (Docket No. STN 50-482). The facility is located in Coffey County, Kansas. This supplement has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission and provides recent information regarding resolution of the open items identified in the SER. Because of the favorable resolution of the items discussed in this report, the staff concludes that the facility can be operated by the applicant without endangering the health and safety of the public

  9. The flawed basis for FDA post-marketing safety decisions: the example of anti-depressants and children.

    Science.gov (United States)

    Klein, Donald F

    2006-04-01

    The FDA (February 3, 2005) issued a black box warning that all antidepressants increase the risk of suicidal thinking and behavior in children and adolescents that must be cited in all advertising as well as included in the package insert. Following this, there was a sharp decrease in antidepressant prescriptions for children with uncertain public health impact. The current black box does not claim that these medications increase the risk of completed suicides, although this is the clear implication of the term 'suicidality'. The interpretation by the press is unequivocal that lethal outcomes prompted this action. This review concludes the following: (1) Since no suicide occurred in clinical trials of approximately 4400 children, the analyses relied upon 'suicidality' as a surrogate. (2) The classification of adverse events by the Columbia group necessarily relied on inferences, because the available evidence was not prospectively collected for this purpose. (3) The data analysis relied on a composite variable labeled 'suicidality', an unvalidated, inappropriate surrogate. Specific criticisms of analytic procedures and inferences are presented. The failure of the FDA's post-marketing surveillance system is reviewed. The data necessary for objective evaluations of possible post-marketing harm cannot be gathered by the current process. Proper prospective post-marketing surveillance by linked computerized medical records is a crucial issue that deserves major public and political attention and prompt action.

  10. U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab.

    Science.gov (United States)

    Hazarika, Maitreyee; Chuk, Meredith K; Theoret, Marc R; Mushti, Sirisha; He, Kun; Weis, Shawna L; Putman, Alexander H; Helms, Whitney S; Cao, Xianhua; Li, Hongshan; Zhao, Hong; Zhao, Liang; Welch, Joel; Graham, Laurie; Libeg, Meredith; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2017-07-15

    On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on a clinically meaningful, durable objective response rate (ORR) in a non-comparative analysis of 120 patients who received 3 mg/kg of nivolumab intravenously every 2 weeks with at least 6-month follow-up in an ongoing, randomized, open-label, active-controlled clinical trial. The ORR as assessed by a blinded independent review committee per RECIST v1.1 was 31.7% (95% confidence interval, 23.5-40.8). Ongoing responses were observed in 87% of responding patients, ranging from 2.6+ to 10+ months. In 13 patients, the response duration was 6 months or longer. The risks of nivolumab, including clinically significant immune-mediated adverse reactions (imARs), were assessed in 268 patients who received at least one dose of nivolumab. The FDA review considered whether the ORR and durations of responses were reasonably likely to predict clinical benefit, the adequacy of the safety database, and systematic approaches to the identification, description, and patient management for imARs in product labeling. Clin Cancer Res; 23(14); 3484-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Bisphosphonates and Nonhealing Femoral Fractures: Analysis of the FDA Adverse Event Reporting System (FAERS) and International Safety Efforts

    Science.gov (United States)

    Edwards, Beatrice J.; Bunta, Andrew D.; Lane, Joseph; Odvina, Clarita; Rao, D. Sudhaker; Raisch, Dennis W.; McKoy, June M.; Omar, Imran; Belknap, Steven M.; Garg, Vishvas; Hahr, Allison J.; Samaras, Athena T.; Fisher, Matthew J.; West, Dennis P.; Langman, Craig B.; Stern, Paula H.

    2013-01-01

    Background: In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. Methods: We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). Results: The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. Conclusions: Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing. PMID:23426763

  12. Beliefs about FDA tobacco regulation, modifiability of cancer risk, and tobacco product comparative harm perceptions: Findings from the HINTS-FDA 2015.

    Science.gov (United States)

    Nguyen, Anh B; Henrie, James; Slavit, Wendy I; Kaufman, Annette R

    2018-05-01

    Smokers who inaccurately believe that FDA evaluates cigarettes for safety hold lower harm perceptions of cigarettes compared to those who do not hold this belief. However, not much is known about associations between beliefs about FDA tobacco regulatory authority and comparative harm perceptions of tobacco products. Data were analyzed from the Health Information National Trends Survey, HINTS-FDA 2015 (N = 3738), which is a cross-sectional, probability-based, nationally representative survey of U.S. non-institutionalized civilian adults aged 18 years or older. Weighted multinomial and logistic regression analyses regressed comparative harm perceptions on sociodemographic factors, beliefs about FDA regulatory authority, perceptions of FDA credibility, and beliefs about modifiability of cancer risk (behavioral cancer causal beliefs and cancer fatalism). Findings indicate that, compared to non-users, current tobacco users are more likely to report believing that e-cigarettes are less harmful than cigarettes, to report believing that some cigarette types may be less harmful than others, and to report believing that tobacco products are safer now than they were five years ago. Awareness of FDA regulatory authority was associated with reporting the belief that tobacco products are safer now than five years ago, that e-cigarettes are less harmful than cigarettes, and that some cigarette types are less harmful than other cigarette types. Believing behavior as a cause of cancer and endorsing cancer fatalism were associated with uncertainty of comparative harm perceptions. Communication efforts can help target inaccurate beliefs by raising awareness about regulation of tobacco products as well as the risks of tobacco products. Published by Elsevier Inc.

  13. An analysis of the warning letters issued by the FDA to pharmaceutical manufacturers regarding misleading health outcomes claims

    Directory of Open Access Journals (Sweden)

    Chatterjee S

    2012-12-01

    Full Text Available Objective: To evaluate the number and type of warning letters issued by the US Food and Drug Administration (FDA to pharmaceutical manufacturers for promotional violations.Methods: Two reviewers downloaded, printed and independently evaluated warning letters issued by the FDA to pharmaceutical manufacturers from years 2003-2008. Misleading claims were broadly classified as clinical, Quality-of-Life (QoL, and economic claims. Clinical claims included claims regarding unsubstantiated efficacy, safety and tolerability, superiority, broadening of indication and/or omission of risk information. QoL claims included unsubstantiated quality of life and/or health-related quality of life claims. Economic claims included any form of claim made on behalf of the pharmaceutical companies related to cost superiority of or cost savings from the drug compared to other drugs in the market.Results: In the 6-year study period, 65 warning letters were issued by FDA, which contained 144 clinical, three QoL, and one economic claim. On an average, 11 warning letters were issued per year. Omission of risk information was the most frequently violated claim (30.6% followed by unsubstantiated efficacy claims (18.6%. Warning letters were primarily directed to manufacturers of cardiovascular (14.6%, anti-microbial (14.6%, and CNS (12.5% drugs. Majority of the claims referenced in warning letters contained promotional materials directed to physicians (57%. Conclusion: The study found that misleading clinical outcome claims formed the majority of the promotional violations, and majority of the claims were directed to physicians. Since inadequate promotion of medications may lead to irrational prescribing, the study emphasizes the importance of disseminating reliable, credible, and scientific information to patients, and more importantly, physicians to protect public health.

  14. 76 FR 35899 - Determination of Regulatory Review Period for Purposes of Patent Extension; MYFORTIC

    Science.gov (United States)

    2011-06-20

    ... market the human drug product and continues until FDA grants permission to market the drug product... phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA approved for marketing the human... marketing or use of the product. FDA has determined that the applicable regulatory review period for...

  15. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Jennifer M Colón

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

  16. Small Area Estimate Maps: Does the FDA Regulate Tobacco? - Small Area Estimates

    Science.gov (United States)

    This metric is defined as a person 18 years of age or older who must have reported that he/she believes that the United States Food and Drug Administration (FDA) regulates tobacco products in the U.S.

  17. 76 FR 20588 - FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities; Public Meeting

    Science.gov (United States)

    2011-04-13

    ...://www.blsmeetings.net/FDAPreventiveControls by April 15, 2011. FDA is holding the public meeting on.... FDAPreventiveCont presentation rols. should be submitted in Microsoft PowerPoint, Microsoft Word, or Adobe...

  18. FDA Response to the Fukushima Dai-ichi Nuclear Power Facility Incident

    Science.gov (United States)

    ... is wholesome, safe to eat, and produced under sanitary conditions. FDA has a team of more than ... shipment. United States Customs and Border Protection (CBP) agents routinely use radiation detection equipment to screen food ...

  19. MedWatch, the FDA Safety Information and Adverse Event Reporting Program

    Science.gov (United States)

    ... Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share Tweet Linkedin Pin it ... approved information that can help patients avoid serious adverse events. Potential Signals of Serious Risks/New Safety ...

  20. Economic Welfare Effects of the FDA Regulation of Tobacco Products on Tobacco Growers

    OpenAIRE

    Tiller, Kelly; Feleke, Shiferaw T.; Starnes, Jane H.

    2011-01-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 (FSPTCA) became federal law on June 22, 2009, authorizing the U.S. Food and Drug Administration (FDA) to regulate the manufacturing and marketing of tobacco products in the country. This study examines the potential economic welfare implications for tobacco farms using the Equilibrium Displacement Model. Results suggest that the FDA regulation of tobacco products could induce a significant fall in domestic cigarette sales, leading ...

  1. [Discussion about traditional Chinese medicine pharmacokinetics study based on first botanical drug approved by FDA].

    Science.gov (United States)

    Huang, Fanghua

    2010-04-01

    Pharmacokinetics study is one of main components of pharmaceuticals development. Food and Drug Administration (FDA) approved Veregen as the first botanical drug in 2006. This article introduced FDA's requirement on pharmacokinetics study of botanical drug and pharmacokinetics studies of Veregen, summarized current requirement and status quo of pharmacokinetics study on traditional Chinese medicine (TCM) and natural medicine in China, and discussed about pharmacokinetics study strategy for TCM and natural medicine.

  2. U.S. Tobacco Growers’ Concern about the Impact of the FDA Regulation of Tobacco Products

    OpenAIRE

    Feleke, Shiferaw T.; Starnes, Jane H.; Tiller, Kelly

    2012-01-01

    The objective of the paper is to establish an empirical relationship between household characteristics and tobacco growers’ perception of the impact of the FDA regulation. A logistic model is applied on primary data that came from the Center for Tobacco Grower Research’s (CTGR’s) 2011 mail survey of tobacco producers. Results indicate that over 80 percent of the sample tobacco growers are concerned about the impact of the FDA regulation. The profiles of growers who reported to be concerned ab...

  3. FDA publishes conflict of interest rules for clinical trials. Food and Drug Administration.

    Science.gov (United States)

    James, J S

    1998-03-06

    The Food and Drug Administration (FDA) published new rules defining conflict of interests between drug companies and medical researchers and clinicians. Certain financial arrangements will need to be disclosed, although the FDA estimates that only one to ten percent of pharmaceutical companies will need to submit disclosures for one or more of their investigators. The purpose of the new rule is to prevent bias in safety and efficacy studies of drugs and medical devices. The full rule is published in the Federal Register.

  4. ADVERTISING, THE FDA, AND THE TOBACCO SETTLEMENT: AS HOPES FOR SETTLEMENT DIM, CHALLENGES OF FDA AUTHORITY AND FIRST AMENDMENT CONCERNS ARE REKINDLED

    OpenAIRE

    Liu, Levi

    1998-01-01

    This discussion will attempt to explore the controversy and dynamics of FDA authority over tobacco advertising and the constitutionality of the existing (although unapproved) restrictions on tobacco advertising, the two major obstacles to the firm establishment of government limitations on the tobacco industry's commercial speech.

  5. Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS

    Directory of Open Access Journals (Sweden)

    Sakaeda Toshiyuki

    2011-10-01

    Full Text Available Abstract Background Previously, adverse event reports (AERs submitted to the US Food and Drug Administration (FDA database were reviewed to confirm platinum agent-associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Results Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals. Conclusions The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection.

  6. Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance

    Science.gov (United States)

    Kramer, Daniel B.; Baker, Matthew; Ransford, Benjamin; Molina-Markham, Andres; Stewart, Quinn; Fu, Kevin; Reynolds, Matthew R.

    2012-01-01

    Background Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients’ stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. Methods We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Results Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Conclusions Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware. PMID:22829874

  7. Software-Related Recalls of Health Information Technology and Other Medical Devices: Implications for FDA Regulation of Digital Health.

    Science.gov (United States)

    Ronquillo, Jay G; Zuckerman, Diana M

    2017-09-01

    Policy Points: Medical software has become an increasingly critical component of health care, yet the regulation of these devices is inconsistent and controversial. No studies of medical devices and software assess the impact on patient safety of the FDA's current regulatory safeguards and new legislative changes to those standards. Our analysis quantifies the impact of software problems in regulated medical devices and indicates that current regulations are necessary but not sufficient for ensuring patient safety by identifying and eliminating dangerous defects in software currently on the market. New legislative changes will further deregulate health IT, reducing safeguards that facilitate the reporting and timely recall of flawed medical software that could harm patients. Medical software has become an increasingly critical component of health care, yet the regulatory landscape for digital health is inconsistent and controversial. To understand which policies might best protect patients, we examined the impact of the US Food and Drug Administration's (FDA's) regulatory safeguards on software-related technologies in recent years and the implications for newly passed legislative changes in regulatory policy. Using FDA databases, we identified all medical devices that were recalled from 2011 through 2015 primarily because of software defects. We counted all software-related recalls for each FDA risk category and evaluated each high-risk and moderate-risk recall of electronic medical records to determine the manufacturer, device classification, submission type, number of units, and product details. A total of 627 software devices (1.4 million units) were subject to recalls, with 12 of these devices (190,596 units) subject to the highest-risk recalls. Eleven of the devices recalled as high risk had entered the market through the FDA review process that does not require evidence of safety or effectiveness, and one device was completely exempt from regulatory review

  8. Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

    Science.gov (United States)

    KuKanich, Butch; Warner, Matt; Hahn, Kevin

    2017-02-01

    OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

  9. Gas separation performance of 6FDA-based polyimides with different chemical structures

    KAUST Repository

    Qiu, Wulin

    2013-10-01

    This work reports the gas separation performance of several 6FDA-based polyimides with different chemical structures, to correlate chemical structure with gas transport properties with a special focus on CO2 and CH 4 transport and plasticization stability of the polyimides membranes relevant to natural gas purification. The consideration of the other gases (He, O2 and N2) provided additional insights regarding effects of backbone structure on detailed penetrant properties. The polyimides studied include 6FDA-DAM, 6FDA-mPDA, 6FDA-DABA, 6FDA-DAM:DABA (3:2), 6FDA-DAM:mPDA (3:2) and 6FDA-mPDA:DABA (3:2). Both pure and binary gas permeation were investigated. The packing density, which is tunable by adjusting monomer type and composition of the various samples, correlated with transport permeability and selectivity. The separation performance of the polyimides for various gas pairs were also plotted for comparison to the upper bound curves, and it was found that this family of materials shows attractive performance. The CO 2 plasticization responses for the un-cross-linked polyimides showed good plasticization resistance to CO2/CH4 mixed gas with 10% CO2; however, only the cross-linked polyimides showed good plasticization resistance under aggressive gas feed conditions (CO 2/CH4 mixed gas with 50% CO2 or pure CO 2). For future work, asymmetric hollow fibers and carbon molecular sieve membranes based on the most attractive members of the family will be considered. © 2013 Elsevier Ltd. All rights reserved.

  10. Single Cigarette Sales: State Differences in FDA Advertising and Labeling Violations, 2014, United States.

    Science.gov (United States)

    Baker, Hannah M; Lee, Joseph G L; Ranney, Leah M; Goldstein, Adam O

    2016-02-01

    Single cigarettes, which are sold without warning labels and often evade taxes, can serve as a gateway for youth smoking. The Family Smoking Prevention and Tobacco Control Act of 2009 gives the US Food and Drug Administration (FDA) authority to regulate the manufacture, distribution, and marketing of tobacco products, including prohibiting the sale of single cigarettes. To enforce these regulations, the FDA conducted over 335,661 inspections between 2010 and September 30, 2014, and allocated over $115 million toward state inspections contracts. To examine differences in single cigarette violations across states and determine if likely correlates of single cigarette sales predict single cigarette violations at the state level. Cross-sectional study of publicly available FDA warning letters from January 1 to July 31, 2014. All 50 states and the District of Columbia. Tobacco retailer inspections conducted by FDA (n = 33 543). State cigarette tax, youth smoking prevalence, poverty, and tobacco production. State proportion of FDA warning letters issued for single cigarette violations. There are striking differences in the number of single cigarette violations found by state, with 38 states producing no warning letters for selling single cigarettes even as state policymakers developed legislation to address retailer sales of single cigarettes. The state proportion of warning letters issued for single cigarettes is not predicted by state cigarette tax, youth smoking, poverty, or tobacco production, P = .12. Substantial, unexplained variation exists in violations of single cigarette sales among states. These data suggest the possibility of differences in implementation of FDA inspections and the need for stronger quality monitoring processes across states implementing FDA inspections. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. US stem cell clinics, patient safety, and the FDA.

    Science.gov (United States)

    Turner, Leigh

    2015-05-01

    Scholarship on patients accessing unproven stem cell interventions is dominated by research addressing 'stem cell tourism' to such countries as China, India, Mexico, and the Ukraine. However, clinics marketing 'adipose-derived mesenchymal stem cell treatments' are proliferating across the USA. These businesses typically claim to operate in compliance with federal regulations, but careful review of their commercial practices suggests that such clinics are marketing unapproved and noncompliant biological drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Credible deterrence: FDA and the Park Doctrine in the 21st century.

    Science.gov (United States)

    O'Leary, Patrick

    2013-01-01

    One of FDA's most powerful enforcement tools is strict liability criminal prosecution of corporate officers under the Park Doctrine. Recent comments by high-ranking FDA officials about using this power more aggressively and recent cases apparently making good on this promise have spurred commentators to call for the doctrine's demise. Critics argue that strict liability for corporate officers violates fundamental notions of fairness and the appropriate relationship between guilt and liability in criminal law. As a response to these critics, this article argues that the Park Doctrine continues to serve a valuable purpose in deterring conduct that endangers the public health and that structural, political, and practical limitations on FDA's use of Park prosecutions have been, and will continue to be, effective protections against the abuses critics fear. This article proposes a model for understanding why and how FDA uses its prosecutorial powers and assesses a sample of recent high-profile prosecutions under this model to argue that the modern "escalation" of Park prosecutions is in fact a continuation of FDA's historical policy.

  13. The FDA's role in medical device clinical studies of human subjects

    Science.gov (United States)

    Saviola, James

    2005-03-01

    This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices.

  14. 75 FR 57045 - Parallel Review of Medical Products

    Science.gov (United States)

    2010-09-17

    ... decision making process for FDA-regulated medical products after they have been approved or cleared by FDA... slow the developer's quest for Medicare coverage. We believe that a parallel review process can furnish... envision that the decision to undertake the parallel review process with respect to a specific product will...

  15. An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

    OpenAIRE

    Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

    2015-01-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigare...

  16. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs

    DEFF Research Database (Denmark)

    Wu, Peng; Nielsen, Thomas Eiland; Clausen, Mads Hartvig

    2016-01-01

    Small-molecule kinase inhibitors (SMKIs), 28 of which are approved by the US Food and Drug Administration (FDA), have been actively pursued as promising targeted therapeutics. Here, we assess the key structural and physicochemical properties, target selectivity and mechanism of function, and ther......Small-molecule kinase inhibitors (SMKIs), 28 of which are approved by the US Food and Drug Administration (FDA), have been actively pursued as promising targeted therapeutics. Here, we assess the key structural and physicochemical properties, target selectivity and mechanism of function...

  17. Levelling the Playing Field: the FDA's Regulation of Nicotine Dependence Products

    OpenAIRE

    Szubin, Adam J.

    1999-01-01

    There is a great need for the increased development and use of nicotine dependence products (NDPs) in this country. A creative regulatory approach, such as the FDA brought to tobacco regulation, could do an enormous amount of good. In the field of NDPs, as in every area of drug regulation, a new regulatory approach will bring with it costs and benefits. As our knowledge advances, the FDA should not be slow to adopt the same aggressive yet flexible approach to NDPs that it has adopted towards ...

  18. Nanotechnology Laboratory Continues Partnership with FDA and National Institute of Standards and Technology | Poster

    Science.gov (United States)

    The NCI-funded Nanotechnology Characterization Laboratory (NCL)—a leader in evaluating promising nanomedicines to fight cancer—recently renewed its collaboration with the U.S. Food and Drug Administration (FDA) and the National Institute of Standards and Technology (NIST) to continue its groundbreaking work on characterizing nanomedicines and moving them toward the clinic. In partnership with NIST and the FDA, NCL has laid a solid, scientific foundation for using the power of nanotechnology to increase the potency and target the delivery

  19. FDA Experience with Medical Countermeasures under the Animal Rule

    Directory of Open Access Journals (Sweden)

    Paul Aebersold

    2012-01-01

    Full Text Available The Food and Drug Administration issued a final rule in May 2002 to permit the Agency to approve drugs or license biological products on the basis of animal efficacy studies for use in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. Only two drugs were approved in the first nine years of the “Animal Rule” despite massive investment by the federal government since 2001 to stimulate development of medical countermeasures to biological threats. This article therefore examines the Food and Drug Administration reviews made public after approval of those two drugs and the public discussion at the Agency's Anti-Infective Drugs Advisory Committee of one biological product under development under the Animal Rule. Despite the paucity of approved drugs or licensed biological products as medical countermeasures, several investigational drugs have been placed in the National Strategic Stockpile for use as medical countermeasures, if needed.

  20. The rosiglitazone decision process at FDA and EMA : What should we learn?

    NARCIS (Netherlands)

    Pouwels, Koen B.; van Grootheest, Kees

    2012-01-01

    In September 2010 the EMA decided to suspend the market authorisation of rosiglitazone, while the FDA decided to restrict the use of rosiglitazone. These actions were taken approximately 10 years after the introduction of rosiglitazone, because rosiglitazone might be associated with an increased

  1. 21 CFR 14.15 - Committees working under a contract with FDA.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Committees working under a contract with FDA. 14.15 Section 14.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... contract is an advisory committee subject to the Federal Advisory Committee Act and this subpart depends...

  2. 21 CFR 111.610 - What records must be made available to FDA?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What records must be made available to FDA? 111.610 Section 111.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING...

  3. 21 CFR 1.378 - What criteria does FDA use to order a detention?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What criteria does FDA use to order a detention? 1.378 Section 1.378 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Administrative Detention of Food for Human or Animal Consumption...

  4. 21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false When does FDA have to issue a decision on an appeal? 1.405 Section 1.405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Administrative Detention of Food for Human or Animal...

  5. 21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How will FDA handle classified information in an informal hearing? 1.406 Section 1.406 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Administrative Detention of Food for Human or...

  6. 21 CFR Appendix A to Part 201 - Examples of Graphic Enhancements Used by FDA

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Examples of Graphic Enhancements Used by FDA A... (CONTINUED) DRUGS: GENERAL LABELING Pt. 201, App. A Appendix A to Part 201—Examples of Graphic Enhancements.... Examples of § 201.66 Standard Labeling and Modified Labeling Formats A. Section 201.66 Standard Labeling...

  7. 76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

    Science.gov (United States)

    2011-05-24

    ... Investigators.'' This draft guidance is intended to assist clinical investigators, industry, and FDA staff in... Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD...-7100). Send one self-addressed adhesive label to assist the office in processing your requests. Submit...

  8. FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | FNLCR

    Science.gov (United States)

    The U.S. Food and Drug Administration (FDA) has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected.  The National Cancer In

  9. FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | FNLCR Staging

    Science.gov (United States)

    The U.S. Food and Drug Administration (FDA) has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected.  The National Cancer In

  10. A Good Year: FDA Approved Nine New Cancer Drugs in 2014

    Science.gov (United States)

    In 2014, the Food and Drug Administration (FDA) approved 41 drugs that had not been approved previously for any indication, the most in nearly 20 years. Of these 41 novel drugs, 9 were approved for the treatment of cancer or cancer-related conditions.

  11. The Pharmaceutical Industry in 2017. An Analysis of FDA Drug Approvals from the Perspective of Molecules.

    Science.gov (United States)

    de la Torre, Beatriz G; Albericio, Fernando

    2018-02-27

    This is an analysis from a chemical point of view of the 46 drugs (34 New Chemical Entities and 12 Biologics) approved by the FDA during 2017. The drugs included in the 2017 "harvest" have been classified on the basis of their chemical structure: biologics (antibodies and proteins); peptides; amino acids and natural products; drug combinations; and small molecules.

  12. Impact of FDA Actions, DTCA, and Public Information on the Market for Pain Medication.

    Science.gov (United States)

    Bradford, W David; Kleit, Andrew N

    2015-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most important classes of prescription drugs used by primary care physicians to manage pain. The NSAID class of products has a somewhat controversial history, around which a complex regulatory and informational environment has developed. This history includes a boxed warning mandated by the Food and Drug Administration (FDA) for all NSAIDs in 2005. We investigate the impact that various information shocks have had on the use of prescription medications for pain in primary care in the USA. We accomplish this by extracting data on nearly 600,000 patients from a unique nationwide electronic medical record database and estimate the probability of any active prescription for the four types of pain medications as a function of FDA actions, advertising, media coverage, and patient characteristics. We find that even after accounting for multiple sources of information, the FDA label changes and boxed warnings had a significant effect on pain medication prescribing. The boxed warning did not have the same impact on the use of all NSAID inhibitors. We find that the boxed warning reduced the use of NSAID COX-2 inhibitor use, which was the focus of much of the press attention. In contrast, however, the warning actually increased the use of non-COX-2 NSAID inhibitors. Thus, the efficacy of the FDA's black box warning is clearly mixed. Copyright © 2014 John Wiley & Sons, Ltd.

  13. One and done: Reasons principal investigators conduct only one FDA-regulated drug trial

    Directory of Open Access Journals (Sweden)

    Amy Corneli, PhD, MPH

    2017-06-01

    Full Text Available Concerns have been raised over the high turnover rate for clinical investigators. Using the U.S. Food and Drug Administration's (FDA Bioresearch Monitoring Information System database, we conducted an online survey to identify factors that affect principal investigators' (PIs decisions to conduct only a single FDA-regulated drug trial. Of the 201 PIs who responded, 54.2% were classified as “one-and-done.” Among these investigators, 28.9% decided for personal reasons to not conduct another trial, and 44.4% were interested in conducting another trial, but no opportunities were available. Three categories of broad barriers were identified as generally burdensome or challenging by the majority of investigators: 1 workload balance (balancing trial implementation with other work obligations and opportunities (63.8%; 2 time requirements (time to initiate and implement trial; investigator and staff time (63.4%; and 3 data and safety reporting (56.5%. Additionally, 46.0% of investigators reported being generally unsatisfied with finance-related issues. These same top three barriers also affected investigators' decisions to no longer conduct FDA-regulated trials. Our findings illuminate three key aspects of investigator turnover. First, they confirm that investigator turnover occurs, as more than half of respondents were truly “one-and-done.” Second, because a large proportion of respondents wanted to conduct more FDA-regulated trials but lacked opportunities to do so, mechanisms that match interested investigators with research sponsors are needed. Third, by focusing on the barriers we identified that affected investigators' decisions to no longer conduct FDA-regulated trials, future efforts to reduce investigator turnover can target issues that matter the most to investigators.

  14. OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

    Science.gov (United States)

    Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

    2016-01-01

    Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

  15. De besluitvorming over werkzaamheid en veiligheid van rosiglitazon bij de FDA en de EMA. Wat zijn de lessen?

    NARCIS (Netherlands)

    Pouwels, Koen; Van Grootheest, Kees

    2013-01-01

    The rosiglitazone decision process at FDA and EMA. What should we learn? In September 2010 the EMA decided to suspend the market authorisation of rosiglitazone while the FDA decided to restrict its use. These actions were taken because rosiglitazone had been associated with an increased risk of

  16. Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands

    NARCIS (Netherlands)

    Bastiaans, D.E.T.; Forcat, S.; Lyall, H.; Cressey, T.R.; Hansudewechakul, R.; Kanjanavanit, S.; Noguera-Julian, A.; Konigs, C.; Inshaw, J.R.; Chalermpantmetagul, S.; Saidi, Y.; Compagnucci, A.; Harper, L.M.; Giaquinto, C.; Colbers, A.P.; Burger, D.M.

    2014-01-01

    BACKGROUND: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval

  17. 76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

    Science.gov (United States)

    2011-07-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... guidance is intended to assist sponsors planning to develop a therapeutic product that depends on the use...

  18. 76 FR 62073 - Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety...

    Science.gov (United States)

    2011-10-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0721] Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety Modernization Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

  19. FDA Adverse Event Reporting System: Recruiting Doctors to Make Surveillance a Little Less Passive.

    Science.gov (United States)

    Mann, Justin M

    2015-01-01

    Within the last few decades, a shift has taken place in FDA's approach to drug development, with greater emphasis put on postmarketing data collection and less on the traditional premarketing scheme. The FDA Adverse Event Reporting System (FAERS) is the primary system for collecting Adverse Events, but has been criticized for years for the low reporting rate into the system and the poor quality of the information submitted. This paper argues that physicians need to be required to submit adverse event reports to FAERS, because such a requirement (1) would produce a greater number of the high quality reports necessary to better determine causality; (2) is merely an extension of physicians' ethical obligations; and (3) aligns with the approach in the Vaccine Adverse Event Reporting System (VAERS). Furthermore, advances in electronic health records can aid in reporting efficiency.

  20. Data Sets Representative of the Structures and Experimental Properties of FDA-Approved Drugs.

    Science.gov (United States)

    Douguet, Dominique

    2018-03-08

    Presented here are several data sets that gather information collected from the labels of the FDA approved drugs: their molecular structures and those of the described active metabolites, their associated pharmacokinetics and pharmacodynamics data, and the history of their marketing authorization by the FDA. To date, 1852 chemical structures have been identified with a molecular weight less than 2000 of which 492 are or have active metabolites. To promote the sharing of data, the original web server was upgraded for browsing the database and downloading the data sets (http://chemoinfo.ipmc.cnrs.fr/edrug3d). It is believed that the multidimensional chemistry-oriented collections are an essential resource for a thorough analysis of the current drug chemical space. The data sets are envisioned as being used in a wide range of endeavors that include drug repurposing, drug design, privileged structures analyses, structure-activity relationship studies, and improving of absorption, distribution, metabolism, and elimination predictive models.

  1. FDA Approves Two HPV Vaccines: Cervarix for Girls, Gardasil for Boys | Division of Cancer Prevention

    Science.gov (United States)

    The FDA has approved a second vaccine to prevent cervical cancer and cervical precancers, the vaccine’s manufacturer, GlaxoSmithKline (GSK), announced last week. The approval is based on data from a large clinical trial showing that the vaccine, Cervarix, prevented precancerous lesions in 93 percent of those who received the full vaccine sequence of three injections over 6 months. |

  2. Participatory surveillance of diabetes device safety: a social media-based complement to traditional FDA reporting.

    Science.gov (United States)

    Mandl, Kenneth D; McNabb, Marion; Marks, Norman; Weitzman, Elissa R; Kelemen, Skyler; Eggleston, Emma M; Quinn, Maryanne

    2014-01-01

    Malfunctions or poor usability of devices measuring glucose or delivering insulin are reportable to the FDA. Manufacturers submit 99.9% of these reports. We test online social networks as a complementary source to traditional FDA reporting of device-related adverse events. Participatory surveillance of members of a non-profit online social network, TuDiabetes.org, from October 2011 to September 2012. Subjects were volunteers from a group within TuDiabetes, actively engaged online in participatory surveillance. They used the free TuAnalyze app, a privacy-preserving method to report detailed clinical information, available through the network. Network members were polled about finger-stick blood glucose monitors, continuous glucose monitors, and insulin delivery devices, including insulin pumps and insulin pens. Of 549 participants, 75 reported device-related adverse events, nearly half (48.0%) requiring intervention from another person to manage the event. Only three (4.0%) of these were reported by participants to the FDA. All TuAnalyze reports contained outcome information compared with 22% of reports to the FDA. Hypoglycemia and hyperglycemia were experienced by 48.0% and 49.3% of participants, respectively. Members of an online community readily engaged in participatory surveillance. While polling distributed online populations does not yield generalizable, denominator-based rates, this approach can characterize risk within online communities using a bidirectional communication channel that enables reach-back and intervention. Engagement of distributed communities in social networks is a viable complementary approach to traditional public health surveillance for adverse events related to medical devices. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Biomarkers of Potential Harm: Summary of an FDA-Sponsored Public Workshop.

    Science.gov (United States)

    Chang, Cindy M; Cheng, Yu-Ching; Cho, Matthew; Mishina, Elena; Del Valle-Pinero, Arseima Y; van Bemmel, Dana; Hatsukami, Dorothy K

    2017-12-14

    Since 2009, the United States (U.S.) Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has had the authority to regulate the manufacture, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers could play an important role across a number of FDA regulatory activities, including assessing new and modified risk tobacco products and identifying and evaluating potential product standards. On April 4-5, 2016, FDA/CTP hosted a public workshop focused on biomarkers of potential harm (BOPH) with participants from government, industry, academia, and other organizations. The workshop was divided into five sessions focused on: 1) overview of BOPH; 2) cardiovascular disease (CVD); 3) chronic obstructive pulmonary disease (COPD); 4) cancer; and 5) new areas of research. The deliberations from the workshop noted some promising BOPH but also highlighted the lack of systematic effort to identify BOPH that would have utility and validity for evaluating tobacco products. Research areas that could further strengthen the applicability of BOPH to tobacco regulatory science include the exploration of composite biomarkers as predictors of disease risk, "omics" biomarkers, and examining biomarkers using existing cohorts, surveys and experimental studies. This paper synthesizes the main findings from the 2016 FDA-sponsored workshop focused on biomarkers of potential harm (BOPH) and highlights research areas that could further strengthen the science around BOPH and their applicability to tobacco regulatory science. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. The FDA Food Safety and Modernization Act and the Exemption for Small Firms

    OpenAIRE

    Pouliot, Sebastien

    2011-01-01

    The FDA Food Safety Modernization Act of 2010 is new legislation that mandates, among other things, new food safety standards. The act includes a clause that exempts small firms from new regulatory requirements. This paper investigates the effects of a small firm exemption from more stringent food safety standards. The model compares food safety, total output and the number of market participants for different food safety regulation with and without an exemption for small firms. The numerical...

  5. Network-Based Real-time Integrated Fire Detection and Alarm (FDA) System with Building Automation

    Science.gov (United States)

    Anwar, F.; Boby, R. I.; Rashid, M. M.; Alam, M. M.; Shaikh, Z.

    2017-11-01

    Fire alarm systems have become increasingly an important lifesaving technology in many aspects, such as applications to detect, monitor and control any fire hazard. A large sum of money is being spent annually to install and maintain the fire alarm systems in buildings to protect property and lives from the unexpected spread of fire. Several methods are already developed and it is improving on a daily basis to reduce the cost as well as increase quality. An integrated Fire Detection and Alarm (FDA) systems with building automation was studied, to reduce cost and improve their reliability by preventing false alarm. This work proposes an improved framework for FDA system to ensure a robust intelligent network of FDA control panels in real-time. A shortest path algorithmic was chosen for series of buildings connected by fiber optic network. The framework shares information and communicates with each fire alarm panels connected in peer to peer configuration and declare the network state using network address declaration from any building connected in network. The fiber-optic connection was proposed to reduce signal noises, thus increasing large area coverage, real-time communication and long-term safety. Based on this proposed method an experimental setup was designed and a prototype system was developed to validate the performance in practice. Also, the distributed network system was proposed to connect with an optional remote monitoring terminal panel to validate proposed network performance and ensure fire survivability where the information is sequentially transmitted. The proposed FDA system is different from traditional fire alarm and detection system in terms of topology as it manages group of buildings in an optimal and efficient manner.Introduction

  6. Warnings without guidance: patient responses to an FDA warning about ezetimibe.

    Science.gov (United States)

    Shrank, William H; Choudhry, Niteesh K; Tong, Angela; Myers, Jessica; Fischer, Michael A; Swanton, Kellie; Slezak, Julie; Brennan, Troyen A; Liberman, Joshua N; Moffit, Susan; Avorn, Jerry; Carpenter, Daniel

    2012-06-01

    In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication. Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication. Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (Pcommunication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.

  7. Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

    Directory of Open Access Journals (Sweden)

    Benjamin Hixon

    2017-02-01

    Full Text Available Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC. The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9% of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%. The three most frequently reported labeling changes were warnings (68.7%, precautions (58.6%, and patient package insert/medication guide (23.2%. Case reports resulted in the greatest number of documented literature types (n = 791, followed by randomized controlled trials (n = 76, and case control/cohort studies (n = 74. Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%, compared to LOE A (17.1%, and LOE C (14.1% (p = 0.007. Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

  8. FDA regulations regarding iodine addition to foods and labeling of foods containing added iodine12

    Science.gov (United States)

    Trumbo, Paula R

    2016-01-01

    The US Food and Drug Administration (FDA) regulates the addition of iodine to infant formulas, the iodization of salt, and the addition of salt and iodine to foods. The required amount of iodine in infant formulas is based on caloric content, and the label must provide the iodine content per 100 kcal. Cuprous iodide and potassium iodide may be added to table salt as a source of dietary iodine at a maximum amount of 0.01%; if added, the label must indicate that the salt is iodized. Table salt to which iodine has not been added must bear the statement, “This salt does not supply iodide, a necessary nutrient.” If a nutrient is to be appropriately added to a food for the purpose of correcting a dietary insufficiency, there should be sufficient scientific information available to demonstrate a nutritional deficiency and/or identify a public health problem. Furthermore, the population groups that would benefit from the proposed fortification should be identified. If iodine is added to a food, the percent Daily Value of iodine must be listed. There are no FDA regulations governing ingredient standards for dietary supplements. As a result, some dietary supplements include iodine and others do not. If a supplement contains iodine, the Supplement Facts label must list iodine as a nutrient ingredient. If iodine is not listed on the Supplement Facts label, then it has not been added. There are similarities between the FDA, which establishes US food regulations and policies, and the Codex Alimentarius (Codex), which develops international food standards and guidelines under the aegis of the FAO and the WHO. Both the FDA and Codex call for the labeling of table salt to indicate fortification with iodine, voluntary labeling of iodine on foods, and a Daily Value (called a Nutrient Reference Value by Codex) of 150 μg for iodine. PMID:27534626

  9. Biomarkers of Tobacco Exposure: Summary of an FDA-Sponsored Public Workshop.

    Science.gov (United States)

    Chang, Cindy M; Edwards, Selvin H; Arab, Aarthi; Del Valle-Pinero, Arseima Y; Yang, Ling; Hatsukami, Dorothy K

    2017-03-01

    Since 2009, the FDA Center for Tobacco Products (CTP) has had the authority to regulate the manufacturing, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers of exposure pertain to actual human exposure to chemicals arising from tobacco use and could play an important role across a number of FDA regulatory activities, including assessing new and modified-risk tobacco products and identifying and evaluating potential product standards. On August 3-4, 2015, FDA/CTP hosted a public workshop focused on biomarkers of exposure with participants from government, industry, academia, and other organizations. The workshop was divided into four sessions focused on: (i) approaches to evaluating and selecting biomarkers; (ii) biomarkers of exposure and relationship to disease risk; (iii) currently used biomarkers of exposure and biomarkers in development; and (iv) biomarkers of exposure and the assessment of smokeless tobacco and electronic nicotine delivery systems. This article synthesizes the main findings from the workshop and highlights research areas that could further strengthen the science around biomarkers of exposure and help determine their application in tobacco product regulation. Cancer Epidemiol Biomarkers Prev; 26(3); 291-302. ©2016 AACR . ©2016 American Association for Cancer Research.

  10. New and incremental FDA black box warnings from 2008 to 2015.

    Science.gov (United States)

    Solotke, Michael T; Dhruva, Sanket S; Downing, Nicholas S; Shah, Nilay D; Ross, Joseph S

    2018-02-01

    The boxed warning (also known as 'black box warning [BBW]') is one of the strongest drug safety actions that the U.S. Food & Drug Administration (FDA) can implement, and often warns of serious risks. The objective of this study was to comprehensively characterize BBWs issued for drugs after FDA approval. We identified all post-marketing BBWs from January 2008 through June 2015 listed on FDA's MedWatch and Drug Safety Communications websites. We used each drug's prescribing information to classify its BBW as new, major update to a preexisting BBW, or minor update. We then characterized these BBWs with respect to pre-specified BBW-specific and drug-specific features. There were 111 BBWs issued to drugs on the US market, of which 29% (n = 32) were new BBWs, 32% (n = 35) were major updates, and 40% (n = 44) were minor updates. New BBWs and major updates were most commonly issued for death (51%) and cardiovascular risk (27%). The new BBWs and major updates impacted 200 drug formulations over the study period, of which 64% were expected to be used chronically and 58% had available alternatives without a BBW. New BBWs and incremental updates to existing BBWs are frequently added to drug labels after regulatory approval.

  11. An Improved Adaptive Received Beamforming for Nested Frequency Offset and Nested Array FDA-MIMO Radar

    Directory of Open Access Journals (Sweden)

    Sibei Cheng

    2018-02-01

    Full Text Available For the conventional FDA-MIMO (frequency diversity array multiple-input-multiple-output Radar with uniform frequency offset and uniform linear array, the DOFs (degrees of freedom of the adaptive beamformer are limited by the number of elements. A better performance—for example, a better suppression for strong interferences and a more desirable trade-off between the main lobe and side lobe—can be achieved with a greater number of DOFs. In order to obtain larger DOFs, this paper researches the signal model of the FDA-MIMO Radar with nested frequency offset and nested array, then proposes an improved adaptive beamforming method that uses the augmented matrix instead of the covariance matrix to calculate the optimum weight vectors and can be used to improve the output performances of FDA-MIMO Radar with the same element number or reduce the element number while maintain the approximate output performances such as the received beampattern, the main lobe width, side lobe depths and the output SINR (signal-to-interference-noise ratio. The effectiveness of the proposed scheme is verified by simulations.

  12. Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008.

    Science.gov (United States)

    Kornfield, Rachel; Watson, Sydeaka; Higashi, Ashley S; Conti, Rena M; Dusetzina, Stacie B; Garfield, Craig F; Dorsey, E Ray; Huskamp, Haiden A; Alexander, G Caleb

    2013-04-01

    This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies-clonidine, guanfacine, and bupropion-was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit.

  13. Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008

    Science.gov (United States)

    Kornfield, Rachel; Watson, Sydeaka; Higashi, Ashley S.; Conti, Rena M.; Dusetzina, Stacie B.; Garfield, Craig F.; Dorsey, E. Ray; Huskamp, Haiden A.; Alexander, G. Caleb

    2014-01-01

    Objective This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. Methods Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. Results In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies—clonidine, guanfacine, and bupropion—was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. Conclusions FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit. PMID:23318985

  14. FDA Approval of PARP Inhibitors and the Impact on Genetic Counseling and Genetic Testing Practices.

    Science.gov (United States)

    Buchtel, Kathryn M; Vogel Postula, Kristen J; Weiss, Shelly; Williams, Carmen; Pineda, Mario; Weissman, Scott M

    2018-02-01

    In December 2014, the FDA approved olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi) for ovarian cancer patients who have failed three or more lines of chemotherapy and have a germline BRCA1/2 mutation identified through a companion diagnostic test (BRACAnalysis CDx™ (CDx™)) offered exclusively by Myriad Genetic Laboratories. This study explored the impact of PARPi/CDx™ on genetic counselors' (GCs) counseling and testing practices. One hundred twenty three GCs responded to an online survey regarding pre- and post-FDA approval referral patterns, testing strategies/influences, and anecdotal experiences with insurance coverage of PARPi for BRCA1/2 positive patients through a non-CDx™ platform. Following PARPi approval, 40% of respondents reported an increase in overall referrals of ovarian cancer patients and 20% had an increase in post-test counseling only referrals. The majority (61.9%) of respondents reported no change in genetic testing strategy, and there was no change in factors influencing choice of testing laboratory. Nearly all (98.1%) respondents who had experience with insurance covering PARPi indicated approval with mutations identified via non-CDx™ testing. Respondents indicated an increase in referral volume following FDA approval of PARPi/CDx™, but did not report changes in testing practices. Respondents were not aware of PARPi insurance coverage denial in the absence of CDx™.

  15. Issues regarding the U.S. F.D.A. Protective Action Guidelines and derived response levels for human food and animal feed

    International Nuclear Information System (INIS)

    Denney, Bruce

    1989-01-01

    Full text: A review of the Food and Drug Administration's (FDA) rationale and methods for determining protective action guidelines (PAGs) and derived response levels (DRLs) (FDAa82, FDAb82) for human food and animal feed reveals the presence of ambiguous and contradictory information that should be clarified in order to improve the usefulness of the guidance. The differences in the criteria used to determine the Preventative and Emergency PAGs and DRLs, for example, are striking. The Preventative PAGs (and DRLs) are based on accepted health physics principles, e.g. risk factors, avoidance of fetal health effects, agricultural models, etc. The Emergency PAGs (and DRLs), however, are based solely on a traditional safety factor of ten. This difference in rationale becomes more conspicuous when the protective actions for these PAGs are compared: preventative protective actions involve low impact actions, e.g. removal of cattle from pasture, storage to allow for radioactive decay, etc., while emergency protective actions involve high impact actions e.g. isolating and condemning food products. These differences result in a contradiction: high impact actions, which may cause considerable problems and loss of income for farmers and food processors, are based on non-technical premises ('tradition'), while the low impact actions, which may only result in minor inconveniences to farmers and food processors, are based on solid scientific principles. Justifying or explaining these differences to farmers or to the media may be very difficult. Clearly there exists a need to review the basis and rationale upon which the Emergency PAGs and DRLs were derived in order to provide a more scientific explanation for their choice and use. In the FDA guidance (FDAa82), references are also made to ALARA and to the use of low-impact actions at doses lower than the PAGs. Although the FDA accepts and endorses the concept of keeping doses as low as reasonably achievable, the FDA does not

  16. 76 FR 66309 - Pilot Program for Parallel Review of Medical Products; Correction

    Science.gov (United States)

    2011-10-26

    ...] Food and Drug Administration [Docket No. FDA-2010-N-0308] Pilot Program for Parallel Review of Medical Products; Correction AGENCY: Food and Drug Administration, Centers for Medicare and Medicaid Services, HHS... technologies to participate in a program of parallel FDA-CMS review. The document was published with an...

  17. FDA MAUDE data on complications with lasers, light sources, and energy-based devices.

    Science.gov (United States)

    Tremaine, Anne Marie; Avram, Mathew M

    2015-02-01

    It is essential for physicians to be fully informed regarding adverse events and malfunctions associated with medical devices that occur in routine practice. There is limited information on this important issue in the medical literature, and it is mostly based on initial studies and case reports. More advanced knowledge regarding device adverse events is necessary to guide physicians towards providing safe treatments. The FDA requires that manufacturers and device users submit medical device reports (MDRs) for suspected injuries from device use or malfunction. The database of MDRs, entitled Manufacturer and User Facility Device Experience (MAUDE) enables the FDA to monitor device performance and identify potential safety issues. We employed the following search strategy to identify reported adverse events. We searched the MAUDE electronic database on the FDA website in December 2013: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm We collected all reported cases between 1991 and December 2013. The search terms utilized included a comprehensive list of device manufacturers, specific product names, and the wavelengths/technology of the devices used in the field of dermatology. Our search yielded 1257 MDRs. Forty-five MDRs were excluded due to insufficient data. The data is broken down into the adverse events observed, such as, but not limited to: blistering, burns, scarring, dyschromia, fat loss, and nerve palsy. The MDRs describe the adverse event and attempt to determine if it was related to device malfunction versus operator error. Radiofrequency devices, diode lasers, and intense pulsed light devices were the most commonly reported devices related to injuries. 1257 MDRs, from a myriad of devices used in dermatology, have been reported to the FDA as of December 2013. Despite the underreporting of adverse events, the MAUDE database is an untapped resource of post-market surveillance of medical devices. The database can offer additional

  18. Effect of high-frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Schlenstedt, C; Shalash, A; Muthuraman, M; Falk, D; Witt, K; Deuschl, G

    2017-01-01

    The aim of this meta-analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post-stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN-DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow-up periods: 6-15, 24-48 and >48 months. For the medication (Med)-Off/stimulation(Stim)-On condition compared with baseline Med-Off, STN-DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6-15, 24-48 and >48 months, respectively (P gait were the predictors of this beneficial effect. STN-DBS significantly improved FOG for the Med-Off/Stim-On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6-15, 24-48 and >48 months, respectively (P analysis showed a robust improvement of gait and FOG by STN-DBS for more than 4 years in the Med-Off/Stim-On condition. No beneficial effect was found for the On state of medication. Pre-operative levodopa responsiveness of global motor performance (UPDRS-III) is the strongest predictor of the effect of deep brain stimulation on gait. © 2016 EAN.

  19. Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.

    Science.gov (United States)

    Fisher, Adam C; Lee, Sau L; Harris, Daniel P; Buhse, Lucinda; Kozlowski, Steven; Yu, Lawrence; Kopcha, Michael; Woodcock, Janet

    2016-12-30

    Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States. Major scientific advancements pressure established regulatory paradigms, especially in the areas of biosimilars, precision medicine, combination products, emerging manufacturing technologies, and the use of real-world data. Pharmaceutical manufacturing is increasingly globalized, prompting the need for more efficient surveillance systems for monitoring product quality. Furthermore, increasing scrutiny and accelerated approval pathways provide a driving force to be even more efficient with limited regulatory resources. To address these regulatory challenges, the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) harbors a rigorous science and research program in core areas that support drug quality review, inspection, surveillance, standards, and policy development. Science and research is the foundation of risk-based quality assessment of new drugs, generic drugs, over-the-counter drugs, and biotechnology products including biosimilars. This is an overview of the science and research activities in OPQ that support the mission of ensuring that safe, effective, and high-quality drugs are available to the American public. Published by Elsevier B.V.

  20. Evaluation of Facebook and Twitter Monitoring to Detect Safety Signals for Medical Products: An Analysis of Recent FDA Safety Alerts.

    Science.gov (United States)

    Pierce, Carrie E; Bouri, Khaled; Pamer, Carol; Proestel, Scott; Rodriguez, Harold W; Van Le, Hoa; Freifeld, Clark C; Brownstein, John S; Walderhaug, Mark; Edwards, I Ralph; Dasgupta, Nabarun

    2017-04-01

    The rapid expansion of the Internet and computing power in recent years has opened up the possibility of using social media for pharmacovigilance. While this general concept has been proposed by many, central questions remain as to whether social media can provide earlier warnings for rare and serious events than traditional signal detection from spontaneous report data. Our objective was to examine whether specific product-adverse event pairs were reported via social media before being reported to the US FDA Adverse Event Reporting System (FAERS). A retrospective analysis of public Facebook and Twitter data was conducted for 10 recent FDA postmarketing safety signals at the drug-event pair level with six negative controls. Social media data corresponding to two years prior to signal detection of each product-event pair were compiled. Automated classifiers were used to identify each 'post with resemblance to an adverse event' (Proto-AE), among English language posts. A custom dictionary was used to translate Internet vernacular into Medical Dictionary for Regulatory Activities (MedDRA ® ) Preferred Terms. Drug safety physicians conducted a manual review to determine causality using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) assessment criteria. Cases were also compared with those reported in FAERS. A total of 935,246 posts were harvested from Facebook and Twitter, from March 2009 through October 2014. The automated classifier identified 98,252 Proto-AEs. Of these, 13 posts were selected for causality assessment of product-event pairs. Clinical assessment revealed that posts had sufficient information to warrant further investigation for two possible product-event associations: dronedarone-vasculitis and Banana Boat Sunscreen--skin burns. No product-event associations were found among the negative controls. In one of the positive cases, the first report occurred in social media prior to signal detection from FAERS, whereas the other case

  1. Use of field-portable XRF analyzers for rapid screening of toxic elements in FDA-regulated products.

    Science.gov (United States)

    Palmer, Peter T; Jacobs, Richard; Baker, Peter E; Ferguson, Kelly; Webber, Siri

    2009-04-08

    Analytical instrumentation continues its amazing evolution, especially in regard to generating ever more sensitive, faster, and reliable measurements. Perhaps the most difficult challenges are making these instruments small enough to use in the field, equipping them with well-designed software that facilitates and simplifies their use by nonexperts while preserving enough of their analytical capabilities to render them useful for a wide variety of applications. Perhaps the most impressive and underappreciated example of instruments that meet these criteria are field-portable X-ray fluorescence (XRF) analyzers. In the past, these analyzers have been routinely used for environmental applications (lead in paint and soil, metal particulates in air samples collected onto filters), geology studies (ore and soil analysis, precious metal identification), and recycling industries (alloy identification). However, their use in the analysis of toxic elements in food, food ingredients, dietary supplements, and medicinal and herbal products, especially within the FDA and regulatory environments, has been surprisingly limited to date. Although XRF will not replace atomic spectrometry techniques such as ICP-MS for sub-parts per million level analyses, it offers a number of significant advantages including minimal sample preparation, high sample throughputs, rapid and definitive identification of many toxic elements, and accurate quantitative results. As should be obvious from many recent news reports on elevated levels of toxic elements in children's lunchboxes, toys, and supplements, field-portable XRF analyzers can fill a very important niche and are becoming increasingly popular for a wide variety of elemental analysis applications. This perspective begins with a brief review of the theory of XRF to highlight the underlying principle, instrumentation, and spectra. It includes a discussion of various analytical figures of merit of XRF to illustrate its strengths and limitations

  2. Estimation of Viable Biomass In Wastewater And Activated Sludge By Determination of ATP, Oxygen Utilization Rate And FDA Hydrolysis

    DEFF Research Database (Denmark)

    Jørgensen, Poul-Erik; Eriksen, T.; Jensen, B.K.

    1992-01-01

    ATP content, oxygen utilization rate (OUR) and fluorescein diacetate (FDA) hydrolysis were tested for the ability to express the amount of viable biomass in wastewater and activated sludge. The relationship between biomass and these activity parameters was established in growth cultures made...... with biomass, while FDA hydrolysis in the sludge failed to show any such correlation. Conversion factors of 3 mg ATP/g dw, 300 mg O2/h g dw and 0.4 A/h (mg dw/ml) for ATP, OUR and FDA methods, respectively, were calculated. When the methods were applied for in situ determinations in four different wastewater...... plants, it was found that ATP content and respiration rate estimated viable biomass to range from 81 to 293 mg dw/g SS for raw wastewater and from 67 to 187 mg dw/g SS for activated sludge with a rather weak correlation between ATP and respiration measurements. The FDA hydrolysis estimated viable biomass...

  3. The FDA and the US direct-to-consumer marketplace for stem cell interventions: a temporal analysis.

    Science.gov (United States)

    Knoepfler, Paul S; Turner, Leigh G

    2018-01-01

    Hundreds of businesses in the US currently advertise a wide range of non-US FDA-approved stem cell interventions. Here we present a novel systematic temporal analysis of US companies engaged in direct-to-consumer marketing of putative stem cell treatments. Between 2009 and 2014, the number of new US stem cell businesses with websites grew rapidly, at least doubling on average every year. From 2014 to 2016, approximately 90-100 new stem cell business websites appeared per year. In contrast, from 2012 to the present, regulatory activity in the form of FDA warning letters has been limited. These data point to a problematic disconnect between a rapidly expanding US direct-to-consumer stem cell industry and limited FDA oversight of this marketplace. More consistent, timely and effective FDA actions are urgently needed.

  4. Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?

    Science.gov (United States)

    Connolly, Gregory N; Alpert, Hillel R

    2014-03-01

    Under the Family Smoking Prevention and Tobacco Control Act (FSPTCA), the Food and Drug Administration (FDA) banned the use of "Lights" descriptors or similar terms on tobacco products that convey messages of reduced risk. Manufacturers eliminated terms explicitly stated and substituted colour name descriptors corresponding to the banned terms. This paper examines whether the tobacco industry complied with or circumvented the law and potential FDA regulatory actions. Philip Morris retailer manuals, manufacturers' annual reports filed with the Massachusetts Department of Public Health, a national public opinion survey, and market-wide cigarette sales data were examined. Manufacturers substituted "Gold" for "Light" and "Silver" for "Ultra-light" in the names of Marlboro sub-brands, and "Blue", "Gold", and "Silver" for banned descriptors in sub-brand names. Percent filter ventilation levels, used to generate the smoke yield ranges associated with "Lights" categories, appear to have been reassigned to the new colour brand name descriptors. Following the ban, 92% of smokers reported they could easily identify their usual brands, and 68% correctly named the package colour associated with their usual brand, while sales for "Lights" cigarettes remained unchanged. Tobacco manufacturers appear to have evaded a critical element of the FSPTCA, the ban on misleading descriptors that convey reduced health risk messages. The FPSTCA provides regulatory mechanisms, including banning these products as adulterated (Section 902). Manufacturers could then apply for pre-market approval as new products and produce evidence for FDA evaluation and determination whether or not sales of these products are in the public health interest.

  5. Association of Attorney Advertising and FDA Action with Prescription Claims: A Time Series Segmented Regression Analysis.

    Science.gov (United States)

    Tippett, Elizabeth C; Chen, Brian K

    2015-12-01

    Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.

  6. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

    Science.gov (United States)

    Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

    2017-01-01

    Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that

  7. Mining FDA drug labels using an unsupervised learning technique - topic modeling

    Directory of Open Access Journals (Sweden)

    Xu Xiaowei

    2011-10-01

    Full Text Available Abstract Background The Food and Drug Administration (FDA approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. Method In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering “topics” that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. Results The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P Conclusions The successful application of topic modeling on the FDA drug labeling demonstrates its potential utility as a hypothesis generation means to infer hidden relationships of concepts such as, in this study, drug safety and therapeutic use

  8. FDA gives final approval to Depo amid concerns over safety, cost and coercion.

    Science.gov (United States)

    1992-11-12

    In October 1992, the US Food and Drug Administration (FDA) approved Depo-Provera for contraceptive use thus increasing the number of available contraceptives to women. Yet USAID has distributed it through its family planning programs in developing countries for many years. It has been available in the US since 1969 for noncontraceptive purposes such as endometrial cancer treatment. More than 30 million women around the world have used it to prevent conception. Today about 9 million women in 90 countries use it. A reason FDA did not approve Depo-Provera is that some studies revealed a link between it and breast tumors and cervical cancer in animals. More recent research conducted by WHO shows no connection with cervical cancer or ovarian cancer. In fact, it demonstrates Depo-Provera may protect against endometrial cancer. Yet it does indicate an insignificant increased risk of breast cancer in younger women. Some research suggests Depo-Provera may decrease bone density leading to osteoporosis and may increase the risk of having a low birth weight infant if the child is conceived before an injection. Evidence exists that it may lead to longer delays in becoming pregnant than other forms of contraception. Still 70% do conceive within 12 months after the last injection. Each Depo-Provera injection delivers a progestin in a water-based solution over 12 weeks resulting in suppressed ovulation. Its failure rate is .5%/year, so Depo-Provera is one of the most effective reversible contraceptive available. The most common side effects are menstrual changes and weight gain (5-15 lbs.). Some contraindications include pregnancy, heart or liver disease, and breast cancer. As of November 1992, the FDA had not announced the cost or whether there would be a reduced price for family planning and public health clinics. Women's health and rights advocates plan on monitoring introduction of Depo-Provera to make sure that women have received comprehensive information and were not

  9. FDA advisory committees meet January 26 on Salk HIV-1 immunogen.

    Science.gov (United States)

    1995-01-06

    Two advisory committees of the Food and Drug Administration (FDA) will meet to consider future trials of the HIV-1 immunogen developed by Dr. Jonas Salk. The Immune Response Corporation has already conducted several studies of the immunogen, and has found improvement in various immunological and other blood tests, and no adverse effects. However, the studies have not been large enough to show conclusively that the treatment has clinical benefit in delaying disease progression. The new, larger trials are intended to demonstrate a delay in disease progression and validate the use of blood-test markers of disease progression for studying an immune-based treatment.

  10. FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer The U.S. Food and Drug Administration (FDA) recently approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected. The National Cancer Institute’s (NCI) Biopharmaceutical Development Program (BDP) at the Frederick National Laboratory for Cancer Research produced ch14.18 for the NCI-sponsored clinical trials that proved the drug’s effectiveness against the disease.

  11. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

    Science.gov (United States)

    Nguyen, Diane; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Montagne, Michael

    2013-01-22

    The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA's first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA.This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997-2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total), followed by the Office of Scientific Investigations (131; 5.3%), and the Office of Compliance (105; 4.3%). During the 2nd Clinton Administration (1997-2000) the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001-2008) it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009-2011) it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by administration: Clinton (122.3 ± 36.4), Bush (29.5

  12. Proposed method to calculate FRMAC intervention levels for the assessment of radiologically contaminated food and comparison of the proposed method to the U.S. FDA's method to calculate derived intervention levels

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Terrence D.; Hunt, Brian D.

    2014-02-01

    This report reviews the method recommended by the U.S. Food and Drug Administration for calculating Derived Intervention Levels (DILs) and identifies potential improvements to the DIL calculation method to support more accurate ingestion pathway analyses and protective action decisions. Further, this report proposes an alternate method for use by the Federal Emergency Radiological Assessment Center (FRMAC) to calculate FRMAC Intervention Levels (FILs). The default approach of the FRMAC during an emergency response is to use the FDA recommended methods. However, FRMAC recommends implementing the FIL method because we believe it to be more technically accurate. FRMAC will only implement the FIL method when approved by the FDA representative on the Federal Advisory Team for Environment, Food, and Health.

  13. Smokers' reactions to FDA regulation of tobacco products: findings from the 2009 ITC United States survey.

    Science.gov (United States)

    Fix, Brian V; O'Connor, Richard J; Fong, Geoffrey T; Borland, Ron; Cummings, K M; Hyland, Andrew

    2011-12-16

    On June 22, 2009, the US FDA was granted the authority to regulate tobacco products through the Family Smoking Prevention and Tobacco Control Act (FSPTCA). The intent is to improve public health through regulations on tobacco product marketing and tobacco products themselves. This manuscript reports baseline data on smokers' attitudes and beliefs on specific issues relevant to the FSPTCA. Between November 2009 and January 2010, a telephone survey among a nationally representative sample of n = 678 smokers in the US was performed as part of the International Tobacco Control (ITC) United States Survey. Participants answered a battery of questions on their attitudes and beliefs about aspects of the FSPTCA. Most smokers were unaware of the new FDA tobacco regulations. Smokers indicated support for banning cigarette promotion and nearly a quarter supported requiring tobacco companies to sell cigarettes in plain packaging. Seventy two percent of smokers supported reducing nicotine levels to make cigarettes less addictive if nicotine was made easily available in non-cigarette form. Most smokers were limited in their understanding of efforts to regulate tobacco products in general. Smokers were supportive of efforts to better inform the public about health risks, restrict advertising, and make tobacco products less addictive.

  14. Smokers' reactions to FDA regulation of tobacco products: Findings from the 2009 ITC United States survey

    Directory of Open Access Journals (Sweden)

    Fix Brian V

    2011-12-01

    Full Text Available Abstract Background On June 22, 2009, the US FDA was granted the authority to regulate tobacco products through the Family Smoking Prevention and Tobacco Control Act (FSPTCA. The intent is to improve public health through regulations on tobacco product marketing and tobacco products themselves. This manuscript reports baseline data on smokers' attitudes and beliefs on specific issues relevant to the FSPTCA. Method Between November 2009 and January 2010, a telephone survey among a nationally representative sample of n = 678 smokers in the US was performed as part of the International Tobacco Control (ITC United States Survey. Participants answered a battery of questions on their attitudes and beliefs about aspects of the FSPTCA. Results Most smokers were unaware of the new FDA tobacco regulations. Smokers indicated support for banning cigarette promotion and nearly a quarter supported requiring tobacco companies to sell cigarettes in plain packaging. Seventy two percent of smokers supported reducing nicotine levels to make cigarettes less addictive if nicotine was made easily available in non-cigarette form. Conclusion Most smokers were limited in their understanding of efforts to regulate tobacco products in general. Smokers were supportive of efforts to better inform the public about health risks, restrict advertising, and make tobacco products less addictive.

  15. Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment.

    Directory of Open Access Journals (Sweden)

    Margot A Cousin

    Full Text Available Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation.

  16. In Vitro Tolerance of Drug-Naive Staphylococcus aureus Strain FDA209P to Vancomycin

    Science.gov (United States)

    Singh, Madhuri; Sasaki, Takashi; Morimoto, Yuh; Hishinuma, Tomomi; Hiramatsu, Keiichi

    2016-01-01

    ABSTRACT The mechanisms underlying bacterial tolerance to antibiotics are unclear. A possible adaptation strategy was explored by exposure of drug-naive methicillin-susceptible Staphylococcus aureus strain FDA209P to vancomycin in vitro. Strains surviving vancomycin treatment (vancomycin survivor strains), which appeared after 96 h of exposure, were slow-growing derivatives of the parent strain. Although the vancomycin MICs for the survivor strains were within the susceptible range, the cytokilling effects of vancomycin at 20-fold the MIC were significantly lower for the survivor strains than for the parent strain. Whole-genome sequencing demonstrated that ileS, encoding isoleucyl-tRNA synthetase (IleRS), was mutated in two of the three vancomycin survivor strains. The IleRS Y723H mutation is located close to the isoleucyl-tRNA contact site and potentially affects the affinity of IleRS binding to isoleucyl-tRNA, thereby inhibiting protein synthesis and leading to vancomycin tolerance. Introduction of the mutation encoding IleRS Y723H into FDA209P by allelic replacement successfully transferred the vancomycin tolerance phenotype. We have identified mutation of ileS to be one of the bona fide genetic events leading to the acquisition of vancomycin tolerance in S. aureus, potentially acting via inhibition of the function of IleRS. PMID:27855063

  17. A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications

    Science.gov (United States)

    Rogstad, Sarah; Faustino, Anneliese; Ruth, Ashley; Keire, David; Boyne, Michael; Park, Jun

    2017-05-01

    The characterization sections of biologics license applications (BLAs) approved by the United States Food and Drug Administration (FDA) between 2000 and 2015 were investigated to examine the extent of the use of mass spectrometry. Mass spectrometry was found to be integral to the characterization of these biotherapeutics. Of the 80 electronically submitted monoclonal antibody and protein biotherapeutic BLAs included in this study, 79 were found to use mass spectrometric workflows for protein or impurity characterization. To further examine how MS is being used in successful BLAs, the applications were filtered based on the type and number of quality attributes characterized, the mass spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved glycan analysis), the methods used to introduce the proteins into the gas phase (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses were conducted over a time course based on the FDA BLA approval to determine if any trends in utilization could be observed over time. Additionally, the different classes of protein-based biotherapeutics among the approved BLAs were clustered to determine if any trends could be attributed to the specific type of biotherapeutic.

  18. Data mining of the public version of the FDA Adverse Event Reporting System.

    Science.gov (United States)

    Sakaeda, Toshiyuki; Tamon, Akiko; Kadoyama, Kaori; Okuno, Yasushi

    2013-01-01

    The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS, formerly AERS) is a database that contains information on adverse event and medication error reports submitted to the FDA. Besides those from manufacturers, reports can be submitted from health care professionals and the public. The original system was started in 1969, but since the last major revision in 1997, reporting has markedly increased. Data mining algorithms have been developed for the quantitative detection of signals from such a large database, where a signal means a statistical association between a drug and an adverse event or a drug-associated adverse event, including the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the information component (IC), and the empirical Bayes geometric mean (EBGM). A survey of our previous reports suggested that the ROR provided the highest number of signals, and the EBGM the lowest. Additionally, an analysis of warfarin-, aspirin- and clopidogrel-associated adverse events suggested that all EBGM-based signals were included in the PRR-based signals, and also in the IC- or ROR-based ones, and that the PRR- and IC-based signals were in the ROR-based ones. In this article, the latest information on this area is summarized for future pharmacoepidemiological studies and/or pharmacovigilance analyses.

  19. High performance ZIF-8/6FDA-DAM mixed matrix membrane for propylene/propane separations

    KAUST Repository

    Zhang, Chen

    2012-02-01

    We report significantly enhanced propylene/propane (C 3H 6/C 3H 8) selectivity in mixed matrix membranes fabricated using 6FDA-DAM polyimide and a zeolitic imidazolate framework (ZIF-8). Equilibrium isotherms and sorption kinetics of C 3H 6 and C 3H 8 at 35°C were studied on a 200nm commercially available ZIF-8 sample produced by BASF. Mixed matrix dense films were formed with 6FDA-DAM and 200nm BASF ZIF-8 particles. SEM imaging showed generally good adhesion between the ZIF-8 and 6FDA-DAM without the need for surface-treating ZIF-8. Pure gas permeation showed significantly enhanced mixed matrix ZIF-8/6FDA-DAM membrane C 3H 6/C 3H 8 separation performance over the pure 6FDA-DAM membrane performance. A C 3H 6 permeability of 56.2Barrer and C 3H 6/C 3H 8 ideal selectivity of 31.0 was found in ZIF-8/6FDA-DAM mixed matrix membrane with 48.0wt% ZIF-8 loading, which are 258% and 150% higher than the pure 6FDA-DAM membrane, respectively for permeability and selectivity. Permeation properties of C 3H 6 and C 3H 8 in ZIF-8 were back-calculated by the Maxwell model for composite permeability using pure gas permeation data, leading to a C 3H 6 permeability of 277Barrer and C 3H 6/C 3H 8 selectivity of 122. Mixed gas permeation also verified that selectivity enhancements were achievable in mixed gas environment by ZIF-8. © 2011 Elsevier B.V.

  20. Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Gilhyang Kim

    2016-11-01

    Full Text Available Background Human epidermal growth factor receptor 2 (HER2 is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP criteria and compare their prognostic significance in UUTUC. Methods HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+ and high (2+, 3+ groups. Results Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001. The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004, but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161 in cancer-specific survival. Conclusions HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

  1. Final environmental statement related to the proposed manufacture of floating nuclear power plants: (Docket No. STN 50-437): Part 2, A generic environmental statement considering the siting and operation of floating nuclear power plants

    International Nuclear Information System (INIS)

    1976-09-01

    The proposed action is the issuance of a manufacturing license to Offshore Power Systems for the startup and operation of a proposed manufacturing facility located at Blount Island, Jacksonville, Florida (Docket No. STN 50-437). No nuclear fuel will be handled or stored at the manufacturing site. The plants will be fueled after they have been towed to and moored within protected basins at specific locations designated by the purchaser and after an operating license has been issued by the Nuclear Regulatory Commission. Each nuclear generating plant, mounted on a floating platform, has a net capacity of 1150 MWe. This energy is provided by a pressurized water reactor steam supply system consisting of a Westinghouse four-loop 3425-MWt unit with an ice-condenser containment system. When one or more of these units is located within a single breakwater, the installation is designated an offshore power station. 226 figs., 95 tabs

  2. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies

    Directory of Open Access Journals (Sweden)

    Nguyen Diane

    2013-01-01

    Full Text Available Abstract Background The United States (US Food and Drug Administration (FDA is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation to pharmaceutical companies. A regulatory letter represents the FDA’s first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA. This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997–2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Methods Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Results Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total, followed by the Office of Scientific Investigations (131; 5.3%, and the Office of Compliance (105; 4.3%. During the 2nd Clinton Administration (1997–2000 the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001–2008 it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009–2011 it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by

  3. Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population.

    Science.gov (United States)

    Kesselheim, Aaron S; Franklin, Jessica M; Kim, Seoyoung C; Seeger, John D; Solomon, Daniel H

    2015-11-01

    A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug. We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval. We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF. Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine. Among gout patients, before Colcrys' market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [-0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions.

  4. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

    Directory of Open Access Journals (Sweden)

    Uebbing L

    2017-04-01

    Full Text Available Lukas Uebbing,1,2,* Lukas Klumpp,1,3,* Gregory K Webster,4 Raimar Löbenberg1 1Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group-Rexall Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Canada; 2Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, 3Institute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt, Germany; 4Global Research and Development, AbbVie Inc., North Chicago, IL, USA *These authors contributed equally to this work Abstract: Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is

  5. Mining FDA drug labels using an unsupervised learning technique--topic modeling.

    Science.gov (United States)

    Bisgin, Halil; Liu, Zhichao; Fang, Hong; Xu, Xiaowei; Tong, Weida

    2011-10-18

    The Food and Drug Administration (FDA) approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs) to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering "topics" that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions) of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA) to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA) was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P<0.05). The identified topics have distinct context that can be directly linked to specific adverse events (e.g., liver injury or kidney injury) or therapeutic application (e.g., antiinfectives for systemic use). We were also able to identify potential adverse events that might arise from specific

  6. Mining FDA drug labels using an unsupervised learning technique - topic modeling

    Science.gov (United States)

    2011-01-01

    Background The Food and Drug Administration (FDA) approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs) to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. Method In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering “topics” that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions) of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA) to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA) was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. Results The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P<0.05). The identified topics have distinct context that can be directly linked to specific adverse events (e.g., liver injury or kidney injury) or therapeutic application (e.g., antiinfectives for systemic use). We were also able to identify potential adverse events that

  7. 75 FR 78714 - Determination of Regulatory Review Period for Purposes of Patent Extension; ANGIOMAX

    Science.gov (United States)

    2010-12-16

    ... market the human drug product and continues until FDA grants permission to market the drug product... phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA approved for marketing the human... regulatory review period, that the approval of ANGIOMAX represented the first permitted commercial marketing...

  8. 76 FR 15322 - Determination of Regulatory Review Period for Purposes of Patent Extension; VPRIV

    Science.gov (United States)

    2011-03-21

    ... market the human drug product and continues until FDA grants permission to market the drug product... phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA recently approved for marketing the... regulatory review period and that the approval of VPRIV represented the first permitted commercial marketing...

  9. 76 FR 37127 - Determination of Regulatory Review Period for Purposes of Patent Extension; XYZAL

    Science.gov (United States)

    2011-06-24

    ... market the human drug product and continues until FDA grants permission to market the drug product... phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA recently approved for marketing the... regulatory review period and that the approval of XYZAL represented the first permitted commercial marketing...

  10. Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

    Science.gov (United States)

    Ourso, André

    2012-01-01

    Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

  11. Frenchay dysarthria assessment (FDA-2) in Parkinson's disease: cross-cultural adaptation and psychometric properties of the European Portuguese version.

    Science.gov (United States)

    Cardoso, Rita; Guimarães, Isabel; Santos, Helena; Loureiro, Rita; Domingos, Josefa; de Abreu, Daisy; Gonçalves, Nilza; Pinto, Serge; Ferreira, Joaquim

    2017-01-01

    Hypokinetic dysarthria is a common symptom in those with Parkinson's disease (PD); there is currently no standardized or validated tool for assessing speech in this population. To translate into European Portuguese (EP) the FDA-2 and perform a cultural adaptation followed by an evaluation of its psychometric properties in PD in a sample of people with PD in different stages of disease progression. Translation, back-translation, experts' analysis, pre-test and final version test were performed. The EP version of the FDA-2 was administered to 80 people with PD (PwP) with dysarthria, feasibility and acceptability, reliability (internal consistency and inter-rater reliability) and validity (face and convergent) were measured. Overall, the EP-FDA-2 proved to be similar to the original demonstrating the same conceptual meanings, semantics, idiomatic and score equivalences. It has good feasibility (missing data dysarthria in PD in clinical practice as in the research field.

  12. An analysis of the FDA Food Safety Modernization Act: protection for consumers and boon for business.

    Science.gov (United States)

    Strauss, Debra M

    2011-01-01

    This article analyzes components of the FDA Food Safety Modernization Act, which was prompted by incidents of food contamination, exploring the history of its passage and explaining its significance, as well as its limitations. As the first time in 70 years that food law has been changed substantially, this new law represents only an initial but significant step in the direction of improving food safety. With bipartisan support from both Congress and the President, this legislation embodies a mandate that food safety is at this moment becoming a priority. As a result, the time is ripe for a reassessment of other areas of food laws--particularly genetically modified foods and the use of milk and meat from cloned animals and their progeny--which are allowed under current U.S. law with no labeling, preapprovals, or post-market monitoring. These areas warrant special regulation consistent with the new proactive policy towards securing the safety of the food supply.

  13. Chiron Vision files FDA application to market intraocular implant for CMV retinitis. Food and Drug Administration.

    Science.gov (United States)

    1995-07-01

    Chiron Corporation and Hoffman-LaRoche announced a filing of a New Drug Application with the Food and Drug Administration (FDA) to market Vitrasert, its intraocular implant which delivers ganciclovir directly to the eye for treatment of CMV retinitis. Clinical trials show that Vitrasert offers a clinical improvement versus intravenous ganciclovir in further delaying progression of CMV retinitis in the treated eye. One study reported that the median time to progression of CMV retinitis was 186 days for eyes receiving Vitrasert compared to 72 days for eyes receiving intravenous ganciclovir therapy. Chiron's intraocular implant contains ganciclovir embedded in a polymer-based system that slowly releases the drug into the eye for up to eight months. Two additional trials are underway. For further information contact the Professional Services Group at Chiron Corporation at (800) 244-7668, select 2.

  14. An analysis of FDA-approved drugs: natural products and their derivatives.

    Science.gov (United States)

    Patridge, Eric; Gareiss, Peter; Kinch, Michael S; Hoyer, Denton

    2016-02-01

    Natural products contribute greatly to the history and landscape of new molecular entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural products and their derivatives represent over one-third of all NMEs. Nearly one-half of these are derived from mammals, one-quarter from microbes and one-quarter from plants. Since the 1930s, the total fraction of natural products has diminished, whereas semisynthetic and synthetic natural product derivatives have increased. Over time, this fraction has also become enriched with microbial natural products, which represent a significant portion of approved antibiotics, including more than two-thirds of all antibacterial NMEs. In recent years, the declining focus on natural products has impacted the pipeline of NMEs from specific classes, and this trend is likely to continue without specific investment in the pursuit of natural products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Implications and challenges for implementation of the FDA's final deeming rule for waterpipe tobacco.

    Science.gov (United States)

    Sutfin, Erin L; Soule, Eric K; McKelvey, Karma; Jenson, Desmond

    2017-06-30

    For the first time, the Food and Drug Administration's (FDAs) Center for Tobacco Products now has regulatory authority over all tobacco products, including waterpipe tobacco. In the rule expanding its authority to cover all tobacco products, the FDA uses largely a one-size-fits-all approach. However, several aspects of waterpipe tobacco smoking make it unique from other tobacco products, which may require more specific, tailored rules. This paper describes the distinct features of waterpipe tobacco products and accessories, and identifies unique challenges to the current regulation posed by this form of tobacco use. Additionally, we highlight the need for further research-generated evidence to support additional rulemaking. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Potential reduction exposure products and FDA tobacco and regulation: a CNS call to action.

    Science.gov (United States)

    Heath, Janie; Andrews, Jeannette; Balkstra, Cindy R

    2004-01-01

    A new generation of tobacco harm reduction products is stirring controversy and confusion among healthcare providers. These products, known as "potential reduction exposure products" (PREPs), can be described in terms of reported scientific evidence, as "the good, the bad, and the ugly." On the good side, there is sufficient scientific evidence to support the use of Commit, a new over-the-counter nicotine lozenge PREP, approved for smoking cessation. On the bad side, there is no scientific evidence to support the use of Ariva, another over-the-counter nicotine lozenge PREP, marketed as an alternative to cigarettes when smoking is restricted. On the ugly side, both of these PREPs are nicotine delivery systems with "candy-like" appearances; however, one (Commit) has the Food and Drug Administration (FDA) approval and the other (Ariva) does not. This article provides an overview of PREPs and strategies to help clinical nurse specialists (CNSs) address tobacco harm reduction issues.

  17. Repurposed FDA-approved drugs targeting genes influencing aging can extend lifespan and healthspan in rotifers.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B; Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey

    2018-04-01

    Pharmaceutical interventions can slow aging in animals, and have advantages because their dose can be tightly regulated and the timing of the intervention can be closely controlled. They also may complement environmental interventions like caloric restriction by acting additively. A fertile source for therapies slowing aging is FDA approved drugs whose safety has been investigated. Because drugs bind to several protein targets, they cause multiple effects, many of which have not been characterized. It is possible that some of the side effects of drugs prescribed for one therapy may have benefits in retarding aging. We used computationally guided drug screening for prioritizing drug targets to produce a short list of candidate compounds for in vivo testing. We applied the virtual ligand screening approach FINDSITE comb for screening potential anti-aging protein targets against FDA approved drugs listed in DrugBank. A short list of 31 promising compounds was screened using a multi-tiered approach with rotifers as an animal model of aging. Primary and secondary survival screens and cohort life table experiments identified four drugs capable of extending rotifer lifespan by 8-42%. Exposures to 1 µM erythromycin, 5 µM carglumic acid, 3 µM capecitabine, and 1 µM ivermectin, extended rotifer lifespan without significant effect on reproduction. Some drugs also extended healthspan, as estimated by mitochondria activity and mobility (swimming speed). Our most promising result is that rotifer lifespan was extended by 7-8.9% even when treatment was started in middle age.

  18. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  19. Development of hybrid fog detection algorithm (FDA) using satellite and ground observation data for nighttime

    Science.gov (United States)

    Kim, So-Hyeong; Han, Ji-Hae; Suh, Myoung-Seok

    2017-04-01

    In this study, we developed a hybrid fog detection algorithm (FDA) using AHI/Himawari-8 satellite and ground observation data for nighttime. In order to detect fog at nighttime, Dual Channel Difference (DCD) method based on the emissivity difference between SWIR and IR1 is most widely used. DCD is good at discriminating fog from other things (middle/high clouds, clear sea and land). However, it is difficult to distinguish fog from low clouds. In order to separate the low clouds from the pixels that satisfy the thresholds of fog in the DCD test, we conducted supplementary tests such as normalized local standard derivation (NLSD) of BT11 and the difference of fog top temperature (BT11) and air temperature (Ta) from NWP data (SST from OSTIA data). These tests are based on the larger homogeneity of fog top than low cloud tops and the similarity of fog top temperature and Ta (SST). Threshold values for the three tests were optimized through ROC analysis for the selected fog cases. In addition, considering the spatial continuity of fog, post-processing was performed to detect the missed pixels, in particular, at edge of fog or sub-pixel size fog. The final fog detection results are presented by fog probability (0 100 %). Validation was conducted by comparing fog detection probability with the ground observed visibility data from KMA. The validation results showed that POD and FAR are ranged from 0.70 0.94 and 0.45 0.72, respectively. The quantitative validation and visual inspection indicate that current FDA has a tendency to over-detect the fog. So, more works which reducing the FAR is needed. In the future, we will also validate sea fog using CALIPSO data.

  20. Comparison of FDA safety and efficacy data for KAMRA and Raindrop corneal inlays

    Directory of Open Access Journals (Sweden)

    Majid Moshirfar

    2017-09-01

    Full Text Available AIM: To provide a side-by-side analysis of the summary of safety and effectiveness data (SSED submitted to the FDA for the KAMRA and Raindrop corneal inlays for the correction of presbyopia. METHODS: SSED reports submitted to the FDA for KAMRA and Raindrop were compared with respect to loss of corrected distance visual acuity (CDVA, adverse event rates, induction of astigmatism, retention of contrast sensitivity, stability of manifest refractive spherical equivalent (MRSE, and achieved monocular uncorrected near visual acuity (UNVA at 24mo. RESULTS: Totally 442/508 of KAMRA patients and 344/373 Raindrop patients remained enrolled in the clinical trials at 24mo. The proportion of KAMRA and Raindrop patients who lost ≥2 lines of CDVA at 24mo was 3.4% and 1%, respectively. The adverse event rate was comparable between the devices. No significant inductions of astigmatism were noted. Both technologies induced a transient myopic shift in MRSE followed by a hyperopic shift and subsequent stabilization. Totally 87% of KAMRA and 98% of Raindrop patients attained a monocular UNVA of J5 (20/40 or better at 24mo, 28% of KAMRA and 67% of Raindrop patients attained a monocular UNVA of J1 (20/20 or better at 24mo. CONCLUSION: Both devices can be considered safe and effective, however, the results of corneal inlay implantation are mixed, and long-term patient satisfaction will likely depend on subjective expectations about the capabilities of the inlays. Variability in surgical technique and postoperative care within and between the two clinical trials diminishes the comparative power of this article.

  1. Comparison of FDA safety and efficacy data for KAMRA and Raindrop corneal inlays

    Science.gov (United States)

    Moshirfar, Majid; Desautels, Jordan D; Wallace, Ryan T; Koen, Nicholas; Hoopes, Phillip C.

    2017-01-01

    AIM To provide a side-by-side analysis of the summary of safety and effectiveness data (SSED) submitted to the FDA for the KAMRA and Raindrop corneal inlays for the correction of presbyopia. METHODS SSED reports submitted to the FDA for KAMRA and Raindrop were compared with respect to loss of corrected distance visual acuity (CDVA), adverse event rates, induction of astigmatism, retention of contrast sensitivity, stability of manifest refractive spherical equivalent (MRSE), and achieved monocular uncorrected near visual acuity (UNVA) at 24mo. RESULTS Totally 442/508 of KAMRA patients and 344/373 Raindrop patients remained enrolled in the clinical trials at 24mo. The proportion of KAMRA and Raindrop patients who lost ≥2 lines of CDVA at 24mo was 3.4% and 1%, respectively. The adverse event rate was comparable between the devices. No significant inductions of astigmatism were noted. Both technologies induced a transient myopic shift in MRSE followed by a hyperopic shift and subsequent stabilization. Totally 87% of KAMRA and 98% of Raindrop patients attained a monocular UNVA of J5 (20/40) or better at 24mo, 28% of KAMRA and 67% of Raindrop patients attained a monocular UNVA of J1 (20/20) or better at 24mo. CONCLUSION Both devices can be considered safe and effective, however, the results of corneal inlay implantation are mixed, and long-term patient satisfaction will likely depend on subjective expectations about the capabilities of the inlays. Variability in surgical technique and postoperative care within and between the two clinical trials diminishes the comparative power of this article. PMID:28944206

  2. AAPS and US FDA Crystal City VI workshop on bioanalytical method validation for biomarkers.

    Science.gov (United States)

    Lowes, Steve; Ackermann, Bradley L

    2016-02-01

    Crystal City VI Workshop on Bioanalytical Method Validation of Biomarkers, Renaissance Baltimore Harborplace Hotel, Baltimore, MD, USA, 28-29 September 2015 The Crystal City VI workshop was organized by the American Association of Pharmaceutical Scientists in association with the US FDA to continue discussion on the bioanalysis of biomarkers. An outcome of the Crystal City V workshop, convened following release of the draft FDA Guidance for Industry on Bioanalytical Methods Validation in 2013 was the need to have further discussion on biomarker methods. Biomarkers ultimately became the sole focal point for Crystal City VI, a meeting attended by approximately 200 people and composed of industry scientists and regulators from around the world. The meeting format included several panel discussions to maximize the opportunity for dialogue among participants. Following an initial session on the general topic of biomarker assays and intended use, more focused sessions were held on chromatographic (LC-MS) and ligand-binding assays. In addition to participation by the drug development community, significant representation was present from clinical testing laboratories. The experience of this latter group, collectively identified as practitioners of CLIA (Clinical Laboratory Improvement Amendments), helped shape the discussion and takeaways from the meeting. While the need to operate within the framework of the current BMV guidance was clearly acknowledged, a general understanding that biomarker methods validation cannot be adequately depicted by current PK-centric guidelines emerged as a consensus from the meeting. This report is not intended to constitute the official proceedings from Crystal City VI, which is expected to be published in early 2016.

  3. Electrosurgical injuries during robot assisted surgery: insights from the FDA MAUDE database

    Science.gov (United States)

    Fuller, Andrew; Vilos, George A.; Pautler, Stephen E.

    2012-02-01

    Introduction: The da Vinci surgical system requires the use of electrosurgical instruments. The re-use of such instruments creates the potential for stray electrical currents from capacitive coupling and/or insulation failure with subsequent injury. The morbidity of such injuries may negate many of the benefits of minimally invasive surgery. We sought to evaluate the rate and nature of electrosurgical injury (ESI) associated with this device. Methods: The Manufacturer and User Facility Device Experience (MAUDE) database is administered by the US Food and Drug Administration (FDA) and reports adverse events related to medical devices in the United States. We analyzed all incidents in the context of robotic surgery between January 2001 and June 2011 to identify those related to the use of electrosurgery. Results: In the past decade, a total of 605 reports have been submitted to the FDA with regard to adverse events related to the da Vinci robotic surgical platform. Of these, 24 (3.9%) were related to potential or actual ESI. Nine out of the 24 cases (37.5%) resulted in additional surgical intervention for repair. There were 6 bowel injuries of which only one was recognized and managed intra-operatively. The remainder required laparotomy between 5 and 8 days after the initial robotic procedure. Additionally, there were 3 skin burns. The remaining cases required conservative management or resulted in no harm. Conclusion: ESI in the context of robotic surgery is uncommon but remains under-recognized and under-reported. Surgeons performing robot assisted surgery should be aware that ESI can occur with robotic instruments and vigilance for intra- and post-operative complications is paramount.

  4. Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice.

    Science.gov (United States)

    Esterly, John S; Steadman, Emily; Scheetz, Marc H

    2011-06-01

    In September 2007, the FDA issued an alert recommending that ceftriaxone and calcium-containing solutions should not be administered to any patient within 48 h of each other. Due to the widespread use of ceftriaxone, significant concern was expressed by the greater healthcare community about the warning, which the FDA eventually retracted in April of 2009. We sought to quantify the impact of the warning on healthcare institutions. A survey was administered to the membership of the Society of Infectious Diseases Pharmacists to quantify perceived changes in ceftriaxone use among healthcare institutions across the United States. A survey of Infectious Diseases experts was conducted. Participants were queried for hospital policies/drug use statistics during two times: immediately after the FDA warning and approximately 13 months post warning (preceding the FDA retraction). Related changes in formulary, drug-use policy, and the number of employee hours that were devoted to addressing the FDA warning were assessed. Ninety-four surveys representing 94 hospital systems were included in the analysis. Approximately half (n = 49, 52%) of respondent institutions enacted at least one drug-use policy change based on the warning; one institution removed ceftriaxone from a clinical protocol. Institutions' final interpretations of the warning differed slightly from initial understanding of the warning, and there was an overall minor decrease in the perceived use of ceftriaxone. The majority of those surveyed (n = 70, 74%) estimated that their respective institutions devoted between 1 and 49 employee hours to address the warning. Hospitals with ID pharmacists had minimal changes to ceftriaxone use after the 2007 FDA warning. Specialized pharmacists may be uniquely situated to help hospitals interpret global recommendations locally.

  5. Cigarette graphic warning labels and smoking prevalence in Canada: a critical examination and reformulation of the FDA regulatory impact analysis.

    Science.gov (United States)

    Huang, Jidong; Chaloupka, Frank J; Fong, Geoffrey T

    2014-03-01

    The estimated effect of cigarette graphic warning labels (GWL) on smoking rates is a key input to the Food and Drug Administration's (FDA) regulatory impact analysis (RIA), required by law as part of its rule-making process. However, evidence on the impact of GWLs on smoking prevalence is scarce. The goal of this paper is to critically analyse FDA's approach to estimating the impact of GWLs on smoking rates in its RIA, and to suggest a path forward to estimating the impact of the adoption of GWLs in Canada on Canadian national adult smoking prevalence. A quasi-experimental methodology was employed to examine the impact of adoption of GWLs in Canada in 2000, using the USA as a control. We found a statistically significant reduction in smoking rates after the adoption of GWLs in Canada in comparison with the USA. Our analyses show that implementation of GWLs in Canada reduced smoking rates by 2.87-4.68 percentage points, a relative reduction of 12.1-19.6%; 33-53 times larger than FDA's estimates of a 0.088 percentage point reduction. We also demonstrated that FDA's estimate of the impact was flawed because it is highly sensitive to the changes in variable selection, model specification, and the time period analysed. Adopting GWLs on cigarette packages reduces smoking prevalence. Applying our analysis of the Canadian GWLs, we estimate that if the USA had adopted GWLs in 2012, the number of adult smokers in the USA would have decreased by 5.3-8.6 million in 2013. Our analysis demonstrates that FDA's approach to estimating the impact of GWLs on smoking rates is flawed. Rectifying these problems before this approach becomes the norm is critical for FDA's effective regulation of tobacco products.

  6. Utilization trends of cervical artificial disc replacement after FDA approval compared with anterior cervical fusion: adoption of new technology.

    Science.gov (United States)

    Lu, Young; McAnany, Steven J; Hecht, Andrew C; Cho, Samuel K; Qureshi, Sheeraz A

    2014-02-01

    Epidemiologic study. To compare the utilization of anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA) in terms of patient and hospital characteristics during the 3 years after Food and Drug Administration (FDA) approval of CDA devices in 2007. There was a surge in CDA adoption in the 3 years prior to FDA approval of CDA devices in 2007. However, utilization trends of CDA versus ACDF since the FDA approval are unknown. The Nationwide Inpatient Sample database was used to identify CDA and ACDF procedures performed in the United States in the 3 years after FDA approval of CDA devices (2008-2010). The frequencies of CDA and ACDF were estimated, stratified by patient and hospital characteristics. Average length of hospital stay and total charges and costs were estimated. Multivariable analysis was performed to identify patient and hospital characteristics associated with CDA utilization. In the 3 years after FDA approval of cervical disc devices, population-adjusted growth rates for CDA and ACDF were 4.9% and 11.8%, respectively (P = 0.6977). Female, African American and Medicaid patients were less likely to receive CDA. CDA was less likely to be performed in patients with cervical spondylotic changes and more likely to be performed in younger and healthier patients. CDA was less likely to be performed in the Midwestern United States or in public hospitals. The prevalence of CDA increased in the 3 years after FDA approval with a growth rate that is approximately twice than that for ACDF. Although there seems to be CDA adoption, CDA growth seemed to have reached a plateau and ACDF still remained the dominant surgical strategy for cervical disc disease. Possible regional, racial, and sex disparities in CDA utilization and a more strict approach in the selection of CDA over traditional ACDF may have impeded rapid adoption of CDA. 3.

  7. Regulatory and scientific issues regarding use of foreign data in support of new drug applications in the United States: an FDA perspective.

    Science.gov (United States)

    Khin, N A; Yang, P; Hung, H M J; Maung-U, K; Chen, Y-F; Meeker-O'Connell, A; Okwesili, P; Yasuda, S U; Ball, L K; Huang, S-M; O'Neill, R T; Temple, R

    2013-08-01

    Globalization of clinical research has led to an increase in clinical trials conducted outside of the United States that are submitted to the US Food and Drug Administration (FDA) in new drug applications. This article discusses the FDA's experience with these submissions in specific therapeutic areas, including the extent of this practice, differences between the effectiveness and safety outcomes of studies conducted inside and outside the United States, and the FDA's approach to acceptance of these trials.

  8. Effects of deep brain stimulation on balance and gait in patients with Parkinson's disease: A systematic neurophysiological review.

    Science.gov (United States)

    Collomb-Clerc, A; Welter, M-L

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs. However, the clinical results to date have been disappointing. In this review, we discuss the effects of DBS of these basal ganglia and brainstem structures on the neurophysiological parameters of gait and balance control in PD patients. Overall, the data suggest that both STN and GPi-DBS improve gait parameters and quiet standing postural control in PD patients, but have no effect or may even aggravate dynamic postural control, in particular with STN-DBS. Conversely, DBS of the SNr and PPN has no effect on gait parameters but improves anticipatory postural adjustments and gait postural control. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Sakaeda

    Full Text Available OBJECTIVE: Adverse event reports (AERs submitted to the US Food and Drug Administration (FDA were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors (statins and to attempt to determine the rank-order of the association. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. CONCLUSIONS: Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  10. Modeling and simulation for medical product development and evaluation : highlights from the FDA-C-Path-ISOP 2013 workshop

    NARCIS (Netherlands)

    Romero, Klaus; Sinha, Vikram; Allerheiligen, Sandra; Danhof, Meindert; Pinheiro, Jose; Kruhlak, Naomi; Wang, Yaning; Wang, Sue-Jane; Sauer, John-Michael; Marier, J. F.; Corrigan, Brian; Rogers, James; Heerspink, H. J. Lambers; Gumbo, Tawanda; Vis, Peter; Watkins, Paul; Morrison, Tina; Gillespie, William; Gordon, Mark Forrest; Stephenson, Diane; Hanna, Debra; Pfister, Marc; Lalonde, Richard; Colatsky, Thomas

    2014-01-01

    Medical-product development has become increasingly challenging and resource-intensive. In 2004, the Food and Drug Administration (FDA) described critical challenges facing medical-product development by establishing the critical path initiative [1]. Priorities identified included the need for

  11. 76 FR 24494 - Draft Guidance for Industry and FDA Staff: Processing/Reprocessing Medical Devices in Health Care...

    Science.gov (United States)

    2011-05-02

    ...] Draft Guidance for Industry and FDA Staff: Processing/ Reprocessing Medical Devices in Health Care... Devices in Health Care Settings: Validation Methods and Labeling.'' The recommendations in this guidance... Staff: Processing/Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling...

  12. 21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What expedited procedures apply when FDA initiates a seizure action against a detained perishable food? 1.383 Section 1.383 Food and Drugs FOOD AND... Administrative Detention of Food for Human or Animal Consumption General Provisions § 1.383 What expedited...

  13. The FDA's decision-making process: isn't it time to temper the principle of protective paternalism?

    Science.gov (United States)

    Brandt, Lawrence J

    2008-05-01

    The authors conducted a well-designed, multinational, large study of women younger than 65 yr of age with irritable bowel syndrome (IBS) with a mixed pattern of diarrhea and constipation (IBS-M) or constipation (IBS-C) and showed that a statistically greater percentage of patients in each group responded to tegaserod compared with patients treated with placebo. Practicality looms large, however, in that the Food and Drug Administration (FDA) disallowed the continued marketing of tegaserod because of cardiovascular safety concerns, and it now is only available under a restricted access program. The wisdom of this decision aside, it is disturbing that the FDA revealed a zero-tolerance for any significant risk of disease when a drug (e.g., tegaserod) was used for a nonlife-threatening condition; the FDA chose to neglect any potential benefit of significant improvement in quality of life, while at the same time allowing the continued availability of sildenifil for erectile dysfunction and other medications (e.g., rosiglitazone and nonsteroidal anti-inflammatory drugs [NSAIDs]), each with a far greater risk of cardiovascular complications. Whether tegaserod will be re-released and, if so, under what conditions, is yet to be determined, as is the question of whether the FDA will decide to allow a more transparent decision-making process with input from all interested parties affected by their decision.

  14. Awareness and trust of the FDA and CDC: Results from a national sample of US adults and adolescents.

    Directory of Open Access Journals (Sweden)

    Sarah D Kowitt

    Full Text Available Trust in government agencies plays a key role in advancing these organizations' agendas, influencing behaviors, and effectively implementing policies. However, few studies have examined the extent to which individuals are aware of and trust the leading United States agencies devoted to protecting the public's health. Using two national samples of adolescents (N = 1,125 and adults (N = 5,014, we examined demographic factors, with a focus on vulnerable groups, as correlates of awareness of and trust in the Centers for Disease Control and Prevention (CDC, Food and Drug Administration (FDA, and the federal government. From nine different weighted and adjusted logistic regression models, we found high levels of awareness of the existence of the FDA and CDC (ranging from 55.7% for adolescents' awareness of the CDC to 94.3% for adults' awareness of the FDA and moderate levels of trust (ranging from a low of 41.8% for adults' trust in the federal government and a high of 78.8% for adolescents' trust of the FDA. In the adolescent and adult samples, awareness was higher among non-Hispanic Blacks and respondents with low numeracy. With respect to trust, few consistent demographic differences emerged. Our findings provide novel insights regarding awareness and trust in the federal government and specific United States public health agencies. Our findings suggest groups to whom these agencies may want to selectively communicate to enhance trust and thus facilitate their communication and regulatory agendas.

  15. Investigating drug repositioning opportunities in FDA drug labels through topic modeling.

    Science.gov (United States)

    Bisgin, Halil; Liu, Zhichao; Kelly, Reagan; Fang, Hong; Xu, Xiaowei; Tong, Weida

    2012-01-01

    Drug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U.S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach. A probabilistic topic model was constructed based on the terms in the Medical Dictionary for Regulatory Activities (MedDRA) that appeared in the Boxed Warning, Warnings and Precautions, and Adverse Reactions sections of the labels of 870 drugs. Fifty-two unique topics, each containing a set of terms, were identified by using topic modeling. The resulting probabilistic topic associations were used to measure the distance (similarity) between drugs. The success of the proposed model was evaluated by comparing a drug and its nearest neighbor (i.e., a drug pair) for common indications found in the Indications and Usage Section of the drug labels. Given a drug with more than three indications, the model yielded a 75% recall, meaning 75% of drug pairs shared one or more common indications. This is significantly higher than the 22% recall rate achieved by random selection. Additionally, the recall rate grows rapidly as the number of drug indications increases and reaches 84% for drugs with 11 indications. The analysis also demonstrated that 65 drugs with a Boxed Warning, which indicates significant risk of serious and possibly life-threatening adverse effects, might be replaced with safer alternatives that do not have a Boxed Warning. In

  16. OS IMPACTOS NO ATIVO IMOBILIZADO DA UNIVERSIDADE FEDERAL DE JUIZ DE FORA (UFJF E SUAS DECORRÊNCIAS PARA O CONTROLE GERENCIAL INSTITUCIONAL A PARTIR DA IMPLANTAÇÃO DA PORTARIA CONJUNTA SPU-STN N. 703/2014

    Directory of Open Access Journals (Sweden)

    Maria Simoni Nascimento Soncin

    2017-01-01

    Full Text Available A atualização do valor contábil dos imóveis ao valor de mercado busca evidenciar a capacidade destes ativos em gerar benefícios econômicos e de prestar serviços de qualidade à sociedade. Objetivou-se com essa pesquisa apresentar a atualização, proposta na Portaria Conjunta SPU/STN N. 703/2014, dos bens imóveis de uso educacional, do campus da Universidade Federal de Juiz de Fora, para averiguar os impactos desse procedimento no subgrupo do ativo Imobilizado e suas decorrências para o controle gerencial. O método utilizado como estratégia de pesquisa foi o estudo de caso, realizado na UFJF, por meio de atualizações dos valores registrados no SPIUnet e de análises horizontal e vertical, no balanço patrimonial, nos anos de 2014 e 2015. Os resultados da pesquisa demonstraram que o impacto no imobilizado é relevante, representando um acréscimo real de 34,36% no patrimônio imobiliário desta Universidade. E, que este procedimento poderá auxiliar o controle gerencial, pois fortalece a credibilidade da informação e a transparência dos atos da gestão pública.   The updating of the book value of real estate to market value seeks to highlight the ability of these assets to generate economic benefits and to provide quality services to society. The objective of this research was to present the update, proposed in Joint Ordinance SPU / STN No. 703/2014, of real estate for educational use, at the campus of the Federal University of Juiz de Fora, to investigate the impacts of this procedure on the subgroup of assets Fixed assets and their consequences for management control. The method used as a research strategy was the case study carried out at the UFJF, through updates of the values recorded in SPIUnet and of horizontal and vertical analyzes in the balance sheet, in the years 2014 and 2015. The results of the research demonstrated that The impact on property, plant and equipment is significant, representing a real increase of 34

  17. Direct-to-Consumer Broadcast Advertisements for Pharmaceuticals: Off-Label Promotion and Adherence to FDA Guidelines.

    Science.gov (United States)

    Klara, Kristina; Kim, Jeanie; Ross, Joseph S

    2018-05-01

    Direct-to-consumer (DTC) advertisements for prescription drugs in the United States are regulated by the Food and Drug Administration (FDA). Off-label promotion, or the advertisement of a drug for an indication not approved by the FDA, is prohibited. Our objective was to examine the presence of off-label promotion in broadcast DTC ads and to assess their adherence to FDA guidelines mandating fair balance in presentation of risks and benefits and prohibiting misleading advertisement claims. All English-language broadcast DTC ads for prescription drugs that aired in the United States from January 2015 to July 2016 were obtained from AdPharm, an online collection of healthcare advertisements. Ad length was measured and adherence to FDA guidelines was assessed for several categories: key regulatory items, indicators of false or misleading ads, and indicators of fair balance in presentation of risks and benefits. Our sample included 97 unique DTC ads, representing 60 unique drugs and 67 unique drug-indication combinations. No ads described drug risks quantitatively, whereas drug efficacy was presented quantitatively in 25 (26%) ads. Thirteen (13%) ads, all for diabetes medications, suggested off-label uses for weight loss and blood pressure reduction. The most commonly advertised drugs were indicated for the treatment of inflammatory conditions (n = 12; 18%), diabetes or diabetic neuropathy (n = 11; 16%), bowel or bladder dysfunction (n = 6; 9%), and infections or allergic reaction (n = 6; 9%). More than three-quarters (n = 51; 76%) advertised drugs to treat chronic conditions. Few broadcast DTC ads were fully compliant with FDA guidelines. The overall quality of information provided in ads was low, and suggestions of off-label promotion were common for diabetes medications. The impact of current DTC ads and off-label marketing on patient and prescriber decisions merits further scrutiny.

  18. 75 FR 21298 - Determination of Regulatory Review Period for Purposes of Patent Extension; VIMPAT -NDA 22-253

    Science.gov (United States)

    2010-04-23

    ... product and continues until FDA grants permission to market the drug product. Although only a portion of a... 35 U.S.C. 156(g)(1)(B). FDA recently approved for marketing the human drug product, VIMPAT... regulatory review period and that the approval of VIMPAT represented the first permitted commercial marketing...

  19. Bringing smart pills to market: FDA regulation of ingestible drug/device combination products.

    Science.gov (United States)

    Avery, Matthew; Liu, Dan

    2011-01-01

    Imagine a pill that, after you swallow it, can track its position in your body. Or imagine a pill that can transmit a message to a doctor to tell him that you have taken your bitter medicine. Pills like this already exist. These so-called smart pills are an emerging type of medical therapy. However, this nascent technology has yet to reach the market and developers of these novel therapies face significant regulatory challenges. This article predicts how the Food and Drug Administration will regulate smart pills and shows how the current regulatory regime is inadequate. The article then proposes modifying the current regulatory regime to encourage development of smart pills and other innovative combination products by: (1) regulating combination products based on their "novel mode of action" rather than their "primary mode of action," (2) creating a marketing approval pathway specifically for combination products, and (3) eliminating regulations that require sponsors to get marketing approval from multiple centers within FDA and providing regulatory guidance specifically for ingestible drug/device combination products.

  20. A History of the Sonocare CST-100: The First FDA-approved HIFU Device

    Science.gov (United States)

    Muratore, Robert

    2006-05-01

    The Sonocare CST-100 Therapeutic Ultrasound System, designed for the treatment of glaucoma, was developed in the 1980s and became the first high intensity focused ultrasound (HIFU) device to receive Food and Drug Administration approval. The system arose from studies done by F.L. Lizzi, Eng.Sc.D., of Riverside Research Institute and D.J. Coleman, M.D., of Cornell Medical Center/New York Hospital on the safety of ultrasound diagnosis of the eye. As safety limits were probed, therapeutic regimes were discovered. Optimization of operational parameters, clinical experience, and engineering design came together through a spin-off company, Sonocare, Inc., formed to produce and market the ophthalmic device. Various precedents were set during the approval process, including the acceptance by the FDA of radiation momentum imparted to an absorber as a measure of acoustic power. Many devices were sold, but the laser industry, grandfathered into the therapeutic field, eventually out-marketed Sonocare. The CST-100 remains as a model of elegant industrial design, and existing units are used daily in HIFU laboratory experiments.

  1. Cloned animal products in the human food chain: FDA should protect American consumers.

    Science.gov (United States)

    Butler, Jennifer E F

    2009-01-01

    Animal cloning is "complex process that lets one exactly copy the genetic, or inherited, traits of an animal." In 1997, Dolly the sheep was the first animal cloned and since then "scientists have used animal cloning to breed dairy cows, beef cattle, poultry, hogs and other species of livestock." Cloned animals are highly attractive to livestock breeders because "cloning essentially produces an identical copy of an animal with superior traits." The main purpose of cloning livestock is "more focused on efficiency and economic benefits of the producer rather than the overall effect of cloning on an animal's physical and mental welfare." The focus of this article is threefold. First, the science behind animal cloning is explained and some potential uses and risks of this technology are explored. Second, FDA's historical evolution, current regulatory authority, and limitations of that authority, is described. Lastly, a new regulatory vision recognizes the realities of 21st century global markets and the dynamic evolution of scientific discovery and technology.

  2. The informational turn in food politics: The US FDA's nutrition label as information infrastructure.

    Science.gov (United States)

    Frohlich, Xaq

    2017-04-01

    This article traces the history of the US FDA regulation of nutrition labeling, identifying an 'informational turn' in the evolving politics of food, diet and health in America. Before nutrition labeling was introduced, regulators actively sought to segregate food markets from drug markets by largely prohibiting health information on food labels, believing such information would 'confuse' the ordinary food consumer. Nutrition labeling's emergence, first in the 1970s as consumer empowerment and then later in the 1990s as a solution to information overload, reflected the belief that it was better to manage markets indirectly through consumer information than directly through command-and-control regulatory architecture. By studying product labels as 'information infrastructure', rather than a 'knowledge fix', the article shows how labels are situated at the center of a legally constructed terrain of inter-textual references, both educational and promotional, that reflects a mix of market pragmatism and evolving legal thought about mass versus niche markets. A change to the label reaches out across a wide informational environment representing food and has direct material consequences for how food is produced, distributed, and consumed. One legacy of this informational turn has been an increasing focus by policymakers, industry, and arguably consumers on the politics of information in place of the politics of the food itself.

  3. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis.

    Directory of Open Access Journals (Sweden)

    Bin Li

    Full Text Available Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP and 85% of spontaneous colorectal cancers (CRC. FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

  4. Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System.

    Science.gov (United States)

    Sanagawa, Akimasa; Hotta, Yuji; Kataoka, Tomoya; Maeda, Yasuhiro; Kondo, Masahiro; Kawade, Yoshihiro; Ogawa, Yoshihiro; Nishikawa, Ryohei; Tohkin, Masahiro; Kimura, Kazunori

    2018-04-16

    We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  5. Docking of calcium-binding protein 1 of Entamoeba histolytica using FDA approved drugs

    Directory of Open Access Journals (Sweden)

    Zahid Ahmad

    2017-11-01

    Full Text Available Objective: To find out an alternative potential inhibitor of Entamoeba histolytica calciumbinding protein 1 (EhCaBP1 through in silico studies. Methods: An attempt was made to find a new FDA approved, and cost effective alternative drug for amoebiasis. Sequence of the EhCaBP1 of Entamoeba histolytica was obtained through searching the UniProt database and protein BLAST was performed. The 3D structure of EhCaBP1 was retrieved from Research Collaboratory for Structural Bioinformatics and visualized using Discovery Studio Visualizer® 3.1. A total of 100 drugs were selected and docked using Patchdock and the different sorts of interactions with the target protein were studied using GS viewer, Ligplot and Discovery Studio visualizer. Results: Among the 100 selected drugs, dolutegravir, cefazedone and ergotamine showed large number of interactions with the target protein. Conclusions: The drugs cefazedone and ergotamine showed twenty and nineteen different sorts of interactions respectively with the target protein. These interactions may lead to metabolic changes and can subsequently stop the growth and cause the death of the parasite. Further investigations and experimental analysis are required to unveil the effects of these drugs.

  6. The analysis of the market success of FDA approvals by probing top 100 bestselling drugs

    Science.gov (United States)

    Polanski, Jaroslaw; Bogocz, Jacek; Tkocz, Aleksandra

    2016-05-01

    Target-oriented drug discovery is the main research paradigm of contemporary drug discovery. In target-oriented approaches, we attempt to maximize in vitro drug potency by finding the optimal fit to the target. This can result in a higher molecular complexity, in particular, the higher molecular weight (MW) of the drugs. However, a comparison of the successful developments of pharmaceuticals with the general trends that can be observed in medicinal chemistry resulted in the conclusion that the so-called molecular obesity is an important reason for the attrition rate of drugs. When analyzing the list of top 100 drug bestsellers versus all of the FDA approvals, we discovered that on average lower-complexity (MW, ADMET score) drugs are winners of the top 100 list in terms of numbers but that, especially, up to some optimal MW value, a higher molecular complexity can pay off with higher incomes. This indicates that slim drugs are doing better but that fat drugs are bigger fishes to catch.

  7. Towards a Computational Analysis of Status and Leadership Styles on FDA Panels

    Science.gov (United States)

    Broniatowski, David A.; Magee, Christopher L.

    Decisions by committees of technical experts are increasingly impacting society. These decision-makers are typically embedded within a web of social relations. Taken as a whole, these relations define an implicit social structure which can influence the decision outcome. Aspects of this structure are founded on interpersonal affinity between parties to the negotiation, on assigned roles, and on the recognition of status characteristics, such as relevant domain expertise. This paper build upon a methodology aimed at extracting an explicit representation of such social structures using meeting transcripts as a data source. Whereas earlier results demonstrated that the method presented here can identify groups of decision-makers with a contextual affinity (i.e., membership in a given medical specialty or voting clique), we now can extract meaningful status hierarchies, and can identify differing facilitation styles among committee chairs. Use of this method is demonstrated on the transcripts of U.S. Food and Drug Administration (FDA) advisory panel meeting transcripts; nevertheless, the approach presented here is extensible to other domains and requires only a meeting transcript as input.

  8. Comprehensive Assessments of RNA-seq by the SEQC Consortium: FDA-Led Efforts Advance Precision Medicine.

    Science.gov (United States)

    Xu, Joshua; Gong, Binsheng; Wu, Leihong; Thakkar, Shraddha; Hong, Huixiao; Tong, Weida

    2016-03-15

    Studies on gene expression in response to therapy have led to the discovery of pharmacogenomics biomarkers and advances in precision medicine. Whole transcriptome sequencing (RNA-seq) is an emerging tool for profiling gene expression and has received wide adoption in the biomedical research community. However, its value in regulatory decision making requires rigorous assessment and consensus between various stakeholders, including the research community, regulatory agencies, and industry. The FDA-led SEquencing Quality Control (SEQC) consortium has made considerable progress in this direction, and is the subject of this review. Specifically, three RNA-seq platforms (Illumina HiSeq, Life Technologies SOLiD, and Roche 454) were extensively evaluated at multiple sites to assess cross-site and cross-platform reproducibility. The results demonstrated that relative gene expression measurements were consistently comparable across labs and platforms, but not so for the measurement of absolute expression levels. As part of the quality evaluation several studies were included to evaluate the utility of RNA-seq in clinical settings and safety assessment. The neuroblastoma study profiled tumor samples from 498 pediatric neuroblastoma patients by both microarray and RNA-seq. RNA-seq offers more utilities than microarray in determining the transcriptomic characteristics of cancer. However, RNA-seq and microarray-based models were comparable in clinical endpoint prediction, even when including additional features unique to RNA-seq beyond gene expression. The toxicogenomics study compared microarray and RNA-seq profiles of the liver samples from rats exposed to 27 different chemicals representing multiple toxicity modes of action. Cross-platform concordance was dependent on chemical treatment and transcript abundance. Though both RNA-seq and microarray are suitable for developing gene expression based predictive models with comparable prediction performance, RNA-seq offers

  9. Comprehensive Assessments of RNA-seq by the SEQC Consortium: FDA-Led Efforts Advance Precision Medicine

    Directory of Open Access Journals (Sweden)

    Joshua Xu

    2016-03-01

    Full Text Available Studies on gene expression in response to therapy have led to the discovery of pharmacogenomics biomarkers and advances in precision medicine. Whole transcriptome sequencing (RNA-seq is an emerging tool for profiling gene expression and has received wide adoption in the biomedical research community. However, its value in regulatory decision making requires rigorous assessment and consensus between various stakeholders, including the research community, regulatory agencies, and industry. The FDA-led SEquencing Quality Control (SEQC consortium has made considerable progress in this direction, and is the subject of this review. Specifically, three RNA-seq platforms (Illumina HiSeq, Life Technologies SOLiD, and Roche 454 were extensively evaluated at multiple sites to assess cross-site and cross-platform reproducibility. The results demonstrated that relative gene expression measurements were consistently comparable across labs and platforms, but not so for the measurement of absolute expression levels. As part of the quality evaluation several studies were included to evaluate the utility of RNA-seq in clinical settings and safety assessment. The neuroblastoma study profiled tumor samples from 498 pediatric neuroblastoma patients by both microarray and RNA-seq. RNA-seq offers more utilities than microarray in determining the transcriptomic characteristics of cancer. However, RNA-seq and microarray-based models were comparable in clinical endpoint prediction, even when including additional features unique to RNA-seq beyond gene expression. The toxicogenomics study compared microarray and RNA-seq profiles of the liver samples from rats exposed to 27 different chemicals representing multiple toxicity modes of action. Cross-platform concordance was dependent on chemical treatment and transcript abundance. Though both RNA-seq and microarray are suitable for developing gene expression based predictive models with comparable prediction performance, RNA

  10. Pure- and Mixed-Gas Permeation Properties of Highly Selective and Plasticization Resistant Hydroxyl-Diamine-Based 6FDA Polyimides for CO2/CH4 Separation

    KAUST Repository

    Alaslai, Nasser Y.

    2016-01-05

    The effect of hydroxyl functionalization on the m-phenylene diamine moiety of 6FDA dianhydride-based polyimides was investigated for gas separation applications. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 atm. The introduction of hydroxyl groups in the diamine moiety of 6FDA-diaminophenol (DAP) and 6FDA-diamino resorcinol (DAR) polyimides tightened the overall polymer structure due to increased charge transfer complex formation compared to unfunctionalized 6FDA-m-phenylene diamine (mPDA). The BET surface areas based on nitrogen adsorption of 6FDA-DAP (54 m2g−1) and of 6FDA-DAR (45 m2g−1) were ~18% and 32% lower than that of 6FDA-mPDA (66 m2g−1). 6FDA-mPDA had a pure-gas CO2 permeability of 14 Barrer and CO2/CH4 selectivity of 70. The hydroxyl-functionalized polyimides 6FDA-DAP and 6FDA-DAR exhibited very high pure-gas CO2/CH4 selectivities of 92 and 94 with moderate CO2 permeability of 11 and 8 Barrer, respectively. It was demonstrated that hydroxyl-containing polyimide membranes maintained very high CO2/CH4 selectivity (~ 75 at CO2 partial pressure of 10 atm) due to CO2 plasticization resistance when tested under high-pressure mixed-gas conditions. Functionalization with hydroxyl groups may thus be a promising strategy towards attaining highly selective polyimides for economical membrane-based natural gas sweetening.

  11. Final environmental statement related to the proposed manufacture of floating nuclear power plants by Offshore Power Systems: (Docket No. STN 50-437): Part 2, A generic environmental statement considering the siting and operation of floating nuclear power plants

    International Nuclear Information System (INIS)

    1976-09-01

    The proposed action is the issuance of a manufacturing license to Offshore Power Systems for the startup and operation of a proposed manufacturing facility located at Blount Island, Jacksonville, Florida (Docket No. STN 50-437). No nuclear fuel will be handled or stored at the manufacturing site. The plants will be fueled after they have been towed to and moored within protected basins at specific locations designated by the purchaser and after an operating license has been issued by the Nuclear Regulatory Commission. Each nuclear generating plant, mounted on a floating platform, has a net capacity of 1150 MWe. This energy is provided by a pressurized water reactor steam supply system consisting of a Westinghouse four-loop 3425-MWt unit with an ice-condenser containment system. When one or more of these units is located within a single breakwater, the installation is designated an offshore power station. Volume 2 contains the siting criteria, regulations, effects of construction, effects of operation, and a safety analysis. 2 figs., 2 tabs

  12. Awareness of the role of science in the FDA regulatory submission process: a survey of the TERMIS-Americas membership.

    Science.gov (United States)

    Johnson, Peter C; Bertram, Tim A; Carty, Neal R; Hellman, Kiki B; Tawil, Bill J; Van Dyke, Mark

    2014-06-01

    The Industry Committee of the Tissue Engineering Regenerative Medicine International Society, Americas Chapter (TERMIS-AM) administered a survey to its membership in 2013 to assess the awareness of science requirements in the U.S. Food and Drug Administration (FDA) regulatory process. One hundred forty-four members responded to the survey. Their occupational and geographical representation was representative of the TERMIS-AM membership as a whole. The survey elicited basic demographic information, the degree to which members were involved in tissue engineering technology development, and their plans for future involvement in such development. The survey then assessed the awareness of general FDA scientific practices as well as specific science requirements for regulatory submissions to the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), and the Office of Combination Projects (OCP). The FDA-specific questions in the survey were culled from guidance documents posted on the FDA web site ( www.fda.gov ). One of the answer options was an opt-out clause that enabled survey respondents to claim a lack of sufficient awareness of the topic to answer the question. This enabled the stratification of respondents on the basis of confidence in the topic. Results indicate that across all occupational groups (academic, business, and government) that are represented in the TERMIS-AM membership, the awareness of FDA science requirements varies markedly. Those who performed best were for-profit company employees, consultants, and government employees; while students, professors, and respondents from outside the USA performed least well. Confidence in question topics was associated with increased correctness in responses across all groups, though the association between confidence and the ability to answer correctly was poorest among students and professors. Though 80% of

  13. An experimental investigation of masking in the US FDA adverse event reporting system database.

    Science.gov (United States)

    Wang, Hsin-wei; Hochberg, Alan M; Pearson, Ronald K; Hauben, Manfred

    2010-12-01

    A phenomenon of 'masking' or 'cloaking' in pharmacovigilance data mining has been described, which can potentially cause signals of disproportionate reporting (SDRs) to be missed, particularly in pharmaceutical company databases. Masking has been predicted theoretically, observed anecdotally or studied to a limited extent in both pharmaceutical company and health authority databases, but no previous publication systematically assesses its occurrence in a large health authority database. To explore the nature, extent and possible consequences of masking in the US FDA Adverse Event Reporting System (AERS) database by applying various experimental unmasking protocols to a set of drugs and events representing realistic pharmacovigilance analysis conditions. This study employed AERS data from 2001 through 2005. For a set of 63 Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms (PTs), disproportionality analysis was carried out with respect to all drugs included in the AERS database, using a previously described urn-model-based algorithm. We specifically sought masking in which drug removal induced an increase in the statistical representation of a drug-event combination (DEC) that resulted in the emergence of a new SDR. We performed a series of unmasking experiments selecting drugs for removal using rational statistical decision rules based on the requirement of a reporting ratio (RR) >1, top-ranked statistical unexpectedness (SU) and relatedness as reflected in the WHO Anatomical Therapeutic Chemical level 4 (ATC4) grouping. In order to assess the possible extent of residual masking we performed two supplemental purely empirical analyses on a limited subset of data. This entailed testing every drug and drug group to determine which was most influential in uncovering masked SDRs. We assessed the strength of external evidence for a causal association for a small number of masked SDRs involving a subset of 29 drugs for which level of evidence

  14. Monitoring Antimicrobial Resistance in the Food Supply Chain and Its Implications for FDA Policy Initiatives.

    Science.gov (United States)

    Zawack, Kelson; Li, Min; Booth, James G; Love, Will; Lanzas, Cristina; Gröhn, Yrjö T

    2016-09-01

    In response to concerning increases in antimicrobial resistance (AMR), the Food and Drug Administration (FDA) has decided to increase veterinary oversight requirements for antimicrobials and restrict their use in growth promotion. Given the high stakes of this policy for the food supply, economy, and human and veterinary health, it is important to rigorously assess the effects of this policy. We have undertaken a detailed analysis of data provided by the National Antimicrobial Resistance Monitoring System (NARMS). We examined the trends in both AMR proportion and MIC between 2004 and 2012 at slaughter and retail stages. We investigated the makeup of variation in these data and estimated the sample and effect size requirements necessary to distinguish an effect of the policy change. Finally, we applied our approach to take a detailed look at the 2005 withdrawal of approval for the fluoroquinolone enrofloxacin in poultry water. Slaughter and retail showed similar trends. Both AMR proportion and MIC were valuable in assessing AMR, capturing different information. Most variation was within years, not between years, and accounting for geographic location explained little additional variation. At current rates of data collection, a 1-fold change in MIC should be detectable in 5 years and a 6% decrease in percent resistance could be detected in 6 years following establishment of a new resistance rate. Analysis of the enrofloxacin policy change showed the complexities of the AMR policy with no statistically significant change in resistance of both Campylobacter jejuni and Campylobacter coli to ciprofloxacin, another second-generation fluoroquinolone. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. FDA drug prescribing warnings: is the black box half empty or half full?

    Science.gov (United States)

    Wagner, Anita K; Chan, K Arnold; Dashevsky, Inna; Raebel, Marsha A; Andrade, Susan E; Lafata, Jennifer Elston; Davis, Robert L; Gurwitz, Jerry H; Soumerai, Stephen B; Platt, Richard

    2006-06-01

    Black box warnings (BBWs) are the Food and Drug Administration's (FDA) strongest labeling requirements for high-risk medicines. It is unknown how frequently physicians prescribe BBW drugs and whether they do so in compliance with the warnings. The purpose of the present study was to assess the frequency of use of BBW medications in ambulatory care and prescribing compliance with BBW recommendations. This retrospective study used automated claims data of 929 958 enrollees in 10 geographically diverse health plans in the United States to estimate frequency of use in ambulatory care of 216 BBW drugs/drug groups between 1/1/99 and 31/6/01. We assessed dispensing compliance with the BBW requirements for selected drugs. During a 30-month period, more than 40% of enrollees received at least one medication that carried a BBW that could potentially apply to them. We found few instances of prescribing during pregnancy of BBW drugs absolutely contra-indicated in pregnancy. There was almost no co-prescribing of contra-indicated drugs with the two QT-interval-prolonging BBW drugs evaluated. Most non-compliance occurred with recommendations for baseline laboratory monitoring (49.6% of all therapy initiations that should have been accompanied by baseline laboratory monitoring were not). Many individuals receive drugs considered to carry the potential for serious risk. For some of these drugs, use is largely consistent with their BBW, while for others it is not. Since it will not be possible to avoid certain drug- associated risks, it will be important to develop effective methods to use BBWs and other methods to minimize risks.

  16. Effects of 31 FDA approved small-molecule kinase inhibitors on isolated rat liver mitochondria.

    Science.gov (United States)

    Zhang, Jun; Salminen, Alec; Yang, Xi; Luo, Yong; Wu, Qiangen; White, Matthew; Greenhaw, James; Ren, Lijun; Bryant, Matthew; Salminen, William; Papoian, Thomas; Mattes, William; Shi, Qiang

    2017-08-01

    The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. The KIs were incubated with mitochondria or submitochondrial particles at concentrations ranging from therapeutic maximal blood concentrations (Cmax) levels to 100-fold Cmax levels. Ten endpoints were measured, including oxygen consumption rate, inner membrane potential, cytochrome c release, swelling, reactive oxygen species, and individual respiratory chain complex (I-V) activities. Of the 31 KIs examined only three including sorafenib, regorafenib and pazopanib, all of which are hepatotoxic, caused significant mitochondrial toxicity at concentrations equal to the Cmax, indicating that mitochondrial toxicity likely contributes to the pathogenesis of hepatotoxicity associated with these KIs. At concentrations equal to 100-fold Cmax, 18 KIs were found to be toxic to mitochondria, and among six KIs with BBW-H, mitochondrial injury was induced by regorafenib, lapatinib, idelalisib, and pazopanib, but not ponatinib, or sunitinib. Mitochondrial liability at 100-fold Cmax had a positive predictive power (PPV) of 72% and negative predictive power (NPV) of 33% in predicting human KI hepatotoxicity as defined by product labeling, with the sensitivity and specificity being 62% and 44%, respectively. Similar predictive power was obtained using the criterion of Cmax ≥1.1 µM or daily dose ≥100 mg. Mitochondrial liability at 1-2.5-fold Cmax showed a 100% PPV and specificity, though the NPV and sensitivity were 32% and 14%, respectively. These data provide novel mechanistic insights into KI hepatotoxicity and indicate that

  17. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-09-16

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive

  18. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie Feng

    2015-09-01

    Full Text Available Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS. While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV, thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin, and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy

  19. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-01-01

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and

  20. A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

    Directory of Open Access Journals (Sweden)

    Peter B Madrid

    Full Text Available BACKGROUND: The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. METHODOLOGY/PRINCIPAL FINDINGS: A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. CONCLUSIONS/SIGNIFICANCE: The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses.

  1. SUMMARY OF 2017 FDA PUBLIC WORKSHOP: ANTIBODY MEDIATED REJECTION IN KIDNEY TRANSPLANTATION.

    Science.gov (United States)

    Velidedeoglu, Ergun; Cavaillé-Coll, Marc W; Bala, Shukal; Belen, Ozlem A; Wang, Yan; Albrecht, Renata

    2018-03-20

    Despite major advances in understanding the pathophysiology of antibody mediated rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs. It appears that early T-cell mediated rejection (TCMR), de novo donor specific antibody (dnDSA) formation and AMR result from patient or physician initiated suboptimal immunosuppression, and represent landmarks in an ongoing process rather than separate events. On April 12-13, 2017, the Food and Drug Administration (FDA) sponsored a public workshop on AMR in kidney transplantation to discuss new advances, importance of immunosuppressive medication nonadherence in dnDSA formation, associations between AMR, cellular rejection, changes in GFR, and challenges of clinical trial design for the prevention and treatment of AMR.Results and ConclusionsKey messages from the workshop are summarized in Table 2. Distinction between type 1 (due to preexisting DSA) and type 2 (due to dnDSA) phenotypes of AMR needs to be considered in patient management and clinical trial design. Standardization and more widespread adoption of routine posttransplant DSA monitoring may permit timely diagnosis and understanding of the natural course of type 2 and chronic AMR. Clinical trial design, especially as related to type 2 and chronic AMR, have specific challenges including the high prevalence of nonadherence in the population at risk, indolent nature of the process until the appearance of graft dysfunction and the absence of accepted surrogate endpoints (SEP). Other challenges include sample size and study duration, which could be mitigated by enrichment strategies.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  2. Review

    Indian Academy of Sciences (India)

    Review. J. Astrophys. Astr., Vol. 36, No. 4, December 2015, pp. 433–445. Line Shape Variability in a Sample of AGN with Broad Lines. D. Ilic1,∗, L. ˇC. Popovic1,2 ... ing from. We give here a comparative review of the line shape variability ..... using the mean continuum flux at 5100 Å and the online calculator for luminosity.

  3. Reviews

    Science.gov (United States)

    2004-01-01

    BOOK REVIEWS (99) Complete A-Z Physics Handbook Science Magic in the Kitchen The Science of Cooking Science Experiments You Can Eat WEB WATCH (101) These journal themes are pasta joke Microwave oven Web links CD REVIEW (104) Electricity and Magnetism, KS3 Big Science Comics

  4. 75 FR 81616 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2010-12-28

    ... Office of Management and Budget Review; Comment Request; Medical Devices; Third Party Review Program... review and clearance. Medical Devices; Third Party Review Program Under the Food and Drug Administration... U.S.C. 360m), directing FDA to accredit persons in the private sector to review certain premarket...

  5. 76 FR 62808 - Pilot Program for Parallel Review of Medical Products

    Science.gov (United States)

    2011-10-11

    ... voluntary participation in the pilot program, as well as the guiding principles the Agencies intend to... 57045), parallel review is intended to reduce the time between FDA marketing approval and CMS national...

  6. Evaluating oversight of human drugs and medical devices: a case study of the FDA and implications for nanobiotechnology.

    Science.gov (United States)

    Paradise, Jordan; Tisdale, Alison W; Hall, Ralph F; Kokkoli, Efrosini

    2009-01-01

    This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration (FDA) using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight.

  7. The liberal state and the rogue agency: FDA's regulation of drugs for mood disorders, 1950s-1970s.

    Science.gov (United States)

    Shorter, Edward

    2008-01-01

    The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into "rogues," regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional "cop" agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions.

  8. FDA-EPA Public Health Guidance on Fish Consumption: A Case Study on Informal Interagency Cooperation in "Shared Regulatory Space".

    Science.gov (United States)

    Holden, Mark

    2015-01-01

    This article is a case study on how administrative agencies interact with each other in cases of shared regulatory jurisdiction. The theoretical literature on the topic of overlapping jurisdiction both (1) makes predictions about how agencies are expected to behave when they share jurisdiction, and (2) in recent iterations argues that overlapping jurisdiction can confer unique policymaking benefits. Through the lens of that theoretical literature, this article examines the relations between the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) regarding the public health risks posed by mercury in fish. It concludes that the FDA-EPA case study (1) corroborates the extant theoretical accounts of how agencies behave in cases of overlapping jurisdiction, (2) supports the conclusion of the recent scholarship that overlapping jurisdiction can confer unique policy benefits, and (3) reveals a few wrinkles not given adequate treatment in the extant literature.

  9. Physicians? Trust in the FDA?s Use of Product-Specific Pathways for Generic Drug Approval

    OpenAIRE

    Kesselheim, Aaron S.; Eddings, Wesley; Raj, Tara; Campbell, Eric G.; Franklin, Jessica M.; Ross, Kathryn M.; Fulchino, Lisa A.; Avorn, Jerry; Gagne, Joshua J.

    2016-01-01

    Background: Generic drugs are cost-effective versions of brand-name drugs approved by the Food and Drug Administration (FDA) following proof of pharmaceutical equivalence and bioequivalence. Generic drugs are widely prescribed by physicians, although there is disagreement over the clinical comparability of generic drugs to brand-name drugs within the physician community. The objective of this survey was to assess physicians' perceptions of generic drugs and the generic drug approval process....

  10. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters.

    Science.gov (United States)

    Kim, Hyosun

    2015-08-25

    For the purpose of understanding the Food and Drug Administration's (FDA's) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. The FDA's warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus begun to keep tabs on social media promotions of

  11. The "natural" aversion: the FDA's reluctance to define a leading food-industry marketing claim, and the pressing need for a workable rule.

    Science.gov (United States)

    Farris, April L

    2010-01-01

    As of 2009, the "natural foods" industry has become a 22.3 billion dollar giant and "all-natural" is the second-leading marketing claim for all new food products. Even in such a flourishing market, the Food and Drug Administration (FDA) has never defined the term "natural" through rulemaking. FDA and the U.S. Department of Agriculture (USDA) have instead created separate, non-identical policy statements governing the use of the term "natural," and FDA has abandoned efforts to define "natural" through rulemaking in the face of more pressing priorities. In absence of any governing federal standard, consumer advocacy groups and warring food industries have attempted to define "natural" to fit their preferences through high-stakes litigation of state law claims, leaving courts free to apply diverging standards without the expertise of FDA. Recent case law from federal district courts and the Supreme Court leaves little hope that FDA's current policy statement will preempt state law causes of action. To prevent a potential patchwork of definitions varying by state, and to create a legitimate standard resting on informed scientific expertise rather than consumer whims, FDA should engage in rulemaking to define the term "natural." This paper concludes by sketching potential formulations for such a rule based on FDA's previous successful rule-making ventures and standards used by natural foods retailers.

  12. Swallowing and deep brain stimulation in Parkinson’s disease: A systematic review

    Science.gov (United States)

    Troche, Michelle S.; Brandimore, Alexandra E.; Foote, Kelly D.; Okun, Michael S.

    2013-01-01

    The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson’s disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. “on” vs. “off”, pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. PMID:23726461

  13. Swallowing and deep brain stimulation in Parkinson's disease: a systematic review.

    Science.gov (United States)

    Troche, Michelle S; Brandimore, Alexandra E; Foote, Kelly D; Okun, Michael S

    2013-09-01

    The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson's disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. "on" vs. "off", pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Pelvic organ prolapse surgical management in Portugal and FDA safety communication have an impact on vaginal mesh.

    Science.gov (United States)

    Mascarenhas, Teresa; Mascarenhas-Saraiva, Miguel; Ricon-Ferraz, Amélia; Nogueira, Paula; Lopes, Fernando; Freitas, Alberto

    2015-01-01

    Pelvic organ prolapse (POP) surgery has lately gained importance in gynecological practice. This study aims to characterize the evolution of POP surgical procedures conducted in Portugal in the last decade and the impact of an FDA 2011 safety communication on mesh POP surgeries. Trends in the surgical management of POP were assessed using the Portuguese National Medical Registry. We considered all records of women with diagnosis of genital prolapse from 1 January 2000 to 31 December 2012. Additionally, we also conducted a survey among members of the Portuguese Society of Urogynecology to evaluate current practices in the surgical management of POP. From 2000 to 2012, 46,819 diagnoses of genital prolapse were registered, with a 105 % increase during the study period (2,368 in 2000 to 4,941 in 2012). POP mesh surgery represented only 6 % of total prolapse diagnoses, but mesh use greatly increased up to 2011, when only a slight increase was registered. Among gynecologists who responded to the questionnaire, there was considerable variability on the procedures of choice to treat POP. Fifty-seven per cent of respondents performed vaginal mesh POP surgery, but only 27 % of those actually reported having changed their practice after the FDA 2011 safety communication. Surgical procedures for POP conducted in Portugal greatly increased over the last decade. The use of surgical meshes is still limited, but despite FDA safety communication it has increased over the years, with a slight increase in 2012, which illustrates the need for further analyses in the coming years.

  15. Reviews

    OpenAIRE

    Revista alicantina de estudios ingleses

    1996-01-01

    Contiene: Jan Pilditch, ed. The Critical Response to Katherine Mansfield. Critical Responses in Arts and Letters. 21. Westport, CT: Greenwood Press, 1996 / reviewed by Ana Belén López Pérez; Edith Wharton. Cartas a Morton Fullerton (1907-1931), (Barcelona, Grijalbo Mondadori, 1995). Ed. Marina Premoli. Translation: Esther Gómez / reviewed by Teresa Gómez Reus; Elizabeth Deeds Ermarth. The English Novel in History: 1840-1895. London and New York: Routledge, 1997 / reviewed by Ángel Pé...

  16. Review

    Indian Academy of Sciences (India)

    2017-04-18

    jbiosci. J. Biosci. 42(2), June 2017, 345–353 * Indian Academy of Sciences. 345. DOI: 10.1007/s12038-017-9681-x. Keywords. Angiogenesis; FRG1; FSHD; neuromuscular disorder; RNA biogenesis. Review. Published online: ...

  17. Reviews.

    Science.gov (United States)

    Radcliffe, George; And Others

    1988-01-01

    Reviews three software packages: 1) a package containing 68 programs covering general topics in chemistry; 2) a package dealing with acid-base titration curves and allows for variables to be changed; 3) a chemistry tutorial and drill package. (MVL)

  18. Reviews.

    Science.gov (United States)

    Greenleaf, Floyd; And Others

    1986-01-01

    Reviews eight textbooks, readers, and books. Topics include Latin America, colonial America, the Carolinians, women in French textbooks, the Vikings, the Soviet Union, nineteenth-century Black America, and Ernest Rutherford. (TRS)

  19. Review

    African Journals Online (AJOL)

    , complications are relatively common and this needs to be considered in patient counseling and clinical decision making. Review: Fertility generally returns after renal transplantation. Approximately 74% of pregnancies in kidney transplant ...

  20. Alternative soaking media for the FDA procedure in the detection of salmonella from tomatoes and spinach leaf using phage magnetoelastic biosensors

    Science.gov (United States)

    Chen, I.-Hsuan; Hu, Jiajia; Wang, Fengen; Horikawa, Shin; Barbaree, James M.; Chin, Bryan A.

    2016-05-01

    Efforts were made to incorporate the phage Magnetoelastic (ME) biosensor in FDA's Spinach Soaking procedures according to FDA 2015 BAM method. Three soaking materials (Lactose broth, LB broth, and Peptone water) and various soaking times were investigated. Using merely 100 Salmonella cells spiked on the produce surfaces, the phage biosensors detected Salmonella within 5 hours when soaking tomatoes in LB broth as opposed to taking up to 24 hours. Salmonella was detected on spinach leaves within 7 hours. These phage ME biosensors provide a promising rapid detection platform using LB broth in FDA's soaking procedures while shortening the incubation period.

  1. Reviews

    OpenAIRE

    Revista alicantina de estudios ingleses

    2000-01-01

    Contiene: Villalba, Estefanía. Claves para interpretar la literatura inglesa. Madrid: Alianza Editorial, 1999,211 p. / reviewed by Eva M. Pérez Rodríguez; Dieter Stein & Rosanna Sornicola (ed.) The Virtues of Language. History in Language, Linguistics and Texts. Number 87. Amsterdam: John Benjamin Pub. Co., 1998 / reviewed by José Manuel Belda Medina; Antonia Sánchez-Macarro and R. Carter (eds.) (1998): Linguistic Choice across Genres: Variation in Spoken and Written English. Amsterd...

  2. Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections.

    Science.gov (United States)

    Keiser, Jennifer; Panic, Gordana; Adelfio, Roberto; Cowan, Noemi; Vargas, Mireille; Scandale, Ivan

    2016-07-01

    Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections. All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models. Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 μM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 μM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 μM) and adults (50 μM), and H. polygyrus L3 (200 μM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively. Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a

  3. Use of the FDA nozzle model to illustrate validation techniques in computational fluid dynamics (CFD) simulations.

    Science.gov (United States)

    Hariharan, Prasanna; D'Souza, Gavin A; Horner, Marc; Morrison, Tina M; Malinauskas, Richard A; Myers, Matthew R

    2017-01-01

    A "credible" computational fluid dynamics (CFD) model has the potential to provide a meaningful evaluation of safety in medical devices. One major challenge in establishing "model credibility" is to determine the required degree of similarity between the model and experimental results for the model to be considered sufficiently validated. This study proposes a "threshold-based" validation approach that provides a well-defined acceptance criteria, which is a function of how close the simulation and experimental results are to the safety threshold, for establishing the model validity. The validation criteria developed following the threshold approach is not only a function of Comparison Error, E (which is the difference between experiments and simulations) but also takes in to account the risk to patient safety because of E. The method is applicable for scenarios in which a safety threshold can be clearly defined (e.g., the viscous shear-stress threshold for hemolysis in blood contacting devices). The applicability of the new validation approach was tested on the FDA nozzle geometry. The context of use (COU) was to evaluate if the instantaneous viscous shear stress in the nozzle geometry at Reynolds numbers (Re) of 3500 and 6500 was below the commonly accepted threshold for hemolysis. The CFD results ("S") of velocity and viscous shear stress were compared with inter-laboratory experimental measurements ("D"). The uncertainties in the CFD and experimental results due to input parameter uncertainties were quantified following the ASME V&V 20 standard. The CFD models for both Re = 3500 and 6500 could not be sufficiently validated by performing a direct comparison between CFD and experimental results using the Student's t-test. However, following the threshold-based approach, a Student's t-test comparing |S-D| and |Threshold-S| showed that relative to the threshold, the CFD and experimental datasets for Re = 3500 were statistically similar and the model could be

  4. Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist.

    Directory of Open Access Journals (Sweden)

    Aaron S Coyner

    Full Text Available To assess the neuroprotective effects of flibanserin (formerly BIMT-17, a dual 5-HT1A agonist and 5-HT2A antagonist, in a light-induced retinopathy model.Albino BALB/c mice were injected intraperitoneally with either vehicle or increasing doses of flibanserin ranging from 0.75 to 15 mg/kg flibanserin. To assess 5-HT1A-mediated effects, BALB/c mice were injected with 10 mg/kg WAY 100635, a 5-HT1A antagonist, prior to 6 mg/kg flibanserin and 5-HT1A knockout mice were injected with 6 mg/kg flibanserin. Injections were administered once immediately prior to light exposure or over the course of five days. Light exposure lasted for one hour at an intensity of 10,000 lux. Retinal structure was assessed using spectral domain optical coherence tomography and retinal function was assessed using electroretinography. To investigate the mechanisms of flibanserin-mediated neuroprotection, gene expression, measured by RT-qPCR, was assessed following five days of daily 15 mg/kg flibanserin injections.A five-day treatment regimen of 3 to 15 mg/kg of flibanserin significantly preserved outer retinal structure and function in a dose-dependent manner. Additionally, a single-day treatment regimen of 6 to 15 mg/kg of flibanserin still provided significant protection. The action of flibanserin was hindered by the 5-HT1A antagonist, WAY 100635, and was not effective in 5-HT1A knockout mice. Creb, c-Jun, c-Fos, Bcl-2, Cast1, Nqo1, Sod1, and Cat were significantly increased in flibanserin-injected mice versus vehicle-injected mice.Intraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection. Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanserin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress. Since flibanserin is already FDA-approved for other indications, the potential to repurpose this drug for treating retinal

  5. The nature, magnitude, and reporting compliance of device-related events for intravenous patient-controlled analgesia in the FDA Manufacturer and User Facility Device Experience (MAUDE) database.

    Science.gov (United States)

    Lawal, Oluwadolapo D; Mohanty, Maitreyee; Elder, Harrison; Skeer, Margie; Erpelding, Nathalie; Lanier, Ryan; Katz, Nathaniel

    2018-04-01

    The aim of this study is to determine the characteristics, magnitude, and the quality of reporting of mandated events involving intravenous patient-controlled analgesia (IV-PCA) devices in the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database; a postmarket surveillance system. We utilized a mixed-methods approach to systematically characterize structured data and text narratives associated with IV-PCA events submitted to MAUDE between 1 January 2011 and 12 September 2016. Of 1,430 IV-PCA events reported during the study period, 6.4% were adverse events (AEs) as identified via structured data fields in the MEDWATCH forms. Upon qualitative review of the narrative texts, 11.0% of events were associated with an unfavorable clinical outcome, which was 71% higher than the incidence of the adverse outcomes reported using the structured data fields. Device-related issues, which were mostly preventable, accounted for 86.9% of events. Of 65 reportable events submitted by manufacturers, 18.5% did not comply with reporting requirements as mandated by law. Patients on IV-PCA continue to experience serious complications as a result of preventable errors. Multi-modal interventions including educational training and the development and adoption of PCA devices with improved safety features are needed to improve safety.

  6. Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans- tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule.

    Science.gov (United States)

    2017-11-22

    This final rule adopts without changes an interim final rule with request for comments published in the Federal Register on March 23, 2017. On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. The Drug Enforcement Administration (DEA) maintains FDA-approved products of oral solutions containing dronabinol in schedule II of the Controlled Substances Act.

  7. Review

    NARCIS (Netherlands)

    Prud’homme van Reine, W.F.

    1998-01-01

    The two published parts of the Desmid Flora of Austria are well-illustrated review volumes on a group of precious freshwater microalgae. Volume 1 contains a pretty, visual key to the genera, completed by figures of one or more characteristic species. In all keys of the separate genera many visual

  8. Review

    NARCIS (Netherlands)

    Kalkman, C.

    1996-01-01

    The first volume of this series was published in 1991, and reviewed in Blumea 38, p. 216. The treatments of volumes 2 and 3 are each based on a doctor’s thesis by the first author, elaborated under supervision of Dr. Panigrahi. Volume 2 contains regional revisions of six genera: Prunus, Prinsepia,

  9. Review

    DEFF Research Database (Denmark)

    Van Den Hazel, H B; Kielland-Brandt, Morten; Winther, Jakob R.

    1996-01-01

    The yeast vacuole, which is equivalent to the lysosome of higher eukaryotes, is one of the best characterized degradative organelles. This review describes the biosynthesis and function of yeast vacuolar proteases. Most of these enzymes are delivered to the vacuole via the early compartments...

  10. Reviews

    NARCIS (Netherlands)

    Adema, Frits

    1995-01-01

    This is the second volume of a revision of Tabernaemontana (Apocynaceae). The volume covers the New World species (44) and the genus Stemmadenia (10 species). This part of the revision of Tabernaemontana comes up to the high standards set in the first volume [see the review by Leenhouts, Blumea 38

  11. Review

    African Journals Online (AJOL)

    2016-03-19

    Dave Richards and Brian Finch. March 19, 2016, Penguin Random House South Africa, ISBN 978-1775842514, pp. 64, full colour. Price US$10.00/GB£6.70. In this review, I shall attempt to convince readers that ... head and slams her book down as the memory arrives. “Oh no. That bird still sends shivers through me!

  12. Review

    NARCIS (Netherlands)

    Kalkman, C.; Adema, F.

    1998-01-01

    This book intends (according to the preface) to afford at once a review, a general outline of what has been accomplished, and a set of signposts for the future. It attempts to do so in three sections on Origin and Diversification of Primitive Land Plants (4 papers), Origin and Diversification of

  13. Review

    NARCIS (Netherlands)

    Wilde, de W.J.J.O.

    1994-01-01

    This review marks the appearance of Volume II, after the publication of Volume I, Pteridophytes and Gymnosperms, in 1990; several more volumes are expected in the future before completion of the Vascular plants as a whole. The present volume contains 73 families out of some 250-500 families which

  14. 78 FR 72894 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2013-12-04

    ... Office of Management and Budget Review; Comment Request; Medical Devices; Third-Party Review Under the... collection of information to OMB for review and clearance. Medical Devices; Third-Party Review Under the Food..., Drug, and Cosmetic Act (21 U.S.C. 360m), directing FDA to accredit persons in the private sector to...

  15. The Tip of the Iceberg of Misleading Online Advertising Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Mintzes, Barbara

    2016-02-18

    Kim's overview of Food and Drug Administration (FDA) regulatory actions from 2005 to 2014 is a comprehensive analysis of the US regulatory experience with online direct-to-consumer advertising (DTCA) of prescription medicines. This experience is of relevance internationally as online DTCA reaches the English-speaking public globally, despite the illegality of DTCA in most countries. The most common violations were omissions or minimizations of risk information, overstatements of efficacy, unsubstantiated claims, and promotion of unapproved ("off-label") use. Nearly one fourth of violations involved cancer drugs, raising additional concerns about patient vulnerability, limited treatment advance, and high costs. Based on content analyses of online DTCA, these cases likely reflect a small proportion of unbalanced and misleading promotional information available on the web. The FDA is only able to review a small proportion of promotional materials submitted to them, due to limited staffing, and the delay between first posting and regulatory action means that many people may be exposed to messages that are found to be inaccurate and misleading. The sheer volume of online DTCA, combined with the ability for content to shift continually, poses unique regulatory challenges. © 2016 by Kerman University of Medical Sciences.

  16. The Tip of the Iceberg of Misleading Online Advertising; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Barbara Mintzes

    2016-05-01

    Full Text Available Kim’s overview of Food and Drug Administration (FDA regulatory actions from 2005 to 2014 is a comprehensive analysis of the US regulatory experience with online direct-to-consumer advertising (DTCA of prescription medicines. This experience is of relevance internationally as online DTCA reaches the English-speaking public globally, despite the illegality of DTCA in most countries. The most common violations were omissions or minimizations of risk information, overstatements of efficacy, unsubstantiated claims, and promotion of unapproved (“off-label” use. Nearly one fourth of violations involved cancer drugs, raising additional concerns about patient vulnerability, limited treatment advance, and high costs. Based on content analyses of online DTCA, these cases likely reflect a small proportion of unbalanced and misleading promotional information available on the web. The FDA is only able to review a small proportion of promotional materials submitted to them, due to limited staffing, and the delay between first posting and regulatory action means that many people may be exposed to messages that are found to be inaccurate and misleading. The sheer volume of online DTCA, combined with the ability for content to shift continually, poses unique regulatory challenges.

  17. The impact of FDA regulatory activities on incident dispensing of LABA-containing medication: 2005-2011.

    Science.gov (United States)

    Baker, Meghan A; Butler, Melissa G; Seymour, Sally; Zhang, Fang; Wu, Yute; Wu, Ann Chen; Levenson, Mark S; Wu, Pingsheng; Iyer, Aarthi; Toh, Sengwee; Iyasu, Solomon; Zhou, Esther H

    2017-09-14

    Evidence of safety issues associated with long-acting beta 2 -agonist (LABA) treatment has led to multiple regulatory activities by the U.S. Food and Drug Administration (FDA) on this class of medications. This study describes the impact of the regulatory activities on incident LABA-containing medication dispensing. A monthly rolling cohort of asthma patients who were eligible to initiate a LABA-containing product was created in the Mini-Sentinel Distributed Database between January 2005 and June 2011. Cohorts of individuals who initiated LABA were examined for the changes in the proportions of single-ingredient to fixed-dose inhaled corticosteroid (ICS)-LABA initiators, appropriate initiation of LABA-containing products, and use of controller medications. The impact of the 2005 and 2010 FDA regulatory activities associated with LABA-containing products was measured using interrupted time series with segmented regression. LABA-containing product initiation was declining prior to the 2005 regulatory activities and continued to decline over the study period, accompanied by increased initiation of fixed dose ICS-LABA among LABA initiators. While the 2010 regulatory activities had no immediate impact on the proportion of LABA initiation in patients with prior controller medication dispensing and/or poor asthma control, there was an increasing positive trend toward LABA initiation in the appropriate patient population after the regulatory activities. The 2005 and 2010 FDA regulatory activities likely had an impact on communicating the safety concerns of LABA products. However, the impact cannot be viewed independent of scientific publications, guidelines for asthma treatment and other regulatory activities.

  18. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    International Nuclear Information System (INIS)

    Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

    2011-01-01

    Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

  19. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  20. Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

    Science.gov (United States)

    Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

    2017-01-01

    Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

  1. [Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

    Science.gov (United States)

    Li, Yuanyuan; Xie, Yanming

    2011-10-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

  2. FDA (Food and Drug Administration) Compliance Program Guidance Manual (FY 88). Section 4. Medical and radiological devices

    International Nuclear Information System (INIS)

    1988-01-01

    The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices

  3. FDA (Food and Drug Administration) Compliance Program Guidance Manual (FY 85). Section 4. Medical and radiological devices

    International Nuclear Information System (INIS)

    1985-01-01

    The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices

  4. FDA-CDC Antimicrobial Resistance Isolate Bank: a Publicly Available Resource To Support Research, Development, and Regulatory Requirements.

    Science.gov (United States)

    Lutgring, Joseph D; Machado, María-José; Benahmed, Faiza H; Conville, Patricia; Shawar, Ribhi M; Patel, Jean; Brown, Allison C

    2018-02-01

    The FDA-CDC Antimicrobial Resistance Isolate Bank was created in July 2015 as a publicly available resource to combat antimicrobial resistance. It is a curated repository of bacterial isolates with an assortment of clinically important resistance mechanisms that have been phenotypically and genotypically characterized. In the first 2 years of operation, the bank offered 14 panels comprising 496 unique isolates and had filled 486 orders from 394 institutions throughout the United States. New panels are being added. Copyright © 2018 American Society for Microbiology.

  5. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop

    Science.gov (United States)

    Duan, J; Kesisoglou, F; Novakovic, J; Amidon, GL; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-01-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled “Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation.”1 The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole‐body framework.2 PMID:28571121

  6. Review

    DEFF Research Database (Denmark)

    Van Den Hazel, H B; Kielland-Brandt, Morten; Winther, Jakob R.

    1996-01-01

    The yeast vacuole, which is equivalent to the lysosome of higher eukaryotes, is one of the best characterized degradative organelles. This review describes the biosynthesis and function of yeast vacuolar proteases. Most of these enzymes are delivered to the vacuole via the early compartments...... of the secretory pathway and the endosome, while one of them is directly imported from the cytoplasm. The proteases are synthesized as precursors which undergo many post-translational modifications before the final active form is generated. Proteolytic activation by developments in the analysis of the functions...

  7. A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

    Directory of Open Access Journals (Sweden)

    Schendel Dolores

    2008-12-01

    Full Text Available Abstract The International Society for the Biological Therapy of Cancer (iSBTc has initiated in collaboration with the United States Food and Drug Administration (FDA a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1 identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2 develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document.

  8. Targeting the β-clamp in Helicobacter pylori with FDA-approved drugs reveals micromolar inhibition by diflunisal.

    Science.gov (United States)

    Pandey, Preeti; Verma, Vijay; Gautam, Gunjan; Kumari, Nilima; Dhar, Suman Kumar; Gourinath, Samudrala

    2017-08-01

    The β-clamp is the processivity-promoting factor for most of the enzymes in prokaryotic DNA replication; hence, it is a crucial drug target. In the present study, we investigated the β-clamp from Helicobacter pylori, aiming to seek potential drug molecules against this gastric-cancer-causing bacterium. An in silico screening of Food and Drug Administration (FDA) approved drugs against the H. pylori β-clamp, followed by its in vitro inhibition using a surface competition approach, yielded the drug diflunisal as a positive initial hit. Diflunisal inhibits the growth of H. pylori in the micromolar range. We determined the structure of diflunisal in complex with the β-clamp to show that the drug binds at subsite I, which is a protein-protein interaction site. Successful identification of FDA-approved molecules against H. pylori may lead to better and faster drug development. © 2017 Federation of European Biochemical Societies.

  9. Reviews

    Science.gov (United States)

    2005-07-01

    WE RECOMMEND When Physics Became King This book delves into the history of science since the 18th century. The History of the Laser An interesting read that will teach you far more than its title suggests. History of Physics Selected Reprints A fascinating collection of physics papers spanning four decades. Datalogging set-ups Five great products from Leybold Didactic’s CASSY range. Videocom Measure motion and convert it to graphs with this great device. Basic Raybox This simple piece of equipment offers great performance. WORTH A LOOK Virtual Physics Lab John Nunn’s software demystifies science using clear illustrations. HANDLE WITH CARE Microchem Electricity Kit This box of equipment for introducing electricity lacks quality. Raymond the Raybox A disappointing raybox. The basic version reviewed on p389 is better. WEB WATCH A rough guide to e-learning.

  10. Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

    Science.gov (United States)

    Kesselheim, A S

    2010-06-01

    In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

  11. Synthesis and characterization of a microporous 6FDA-polyimide made from a novel carbocyclic pseudo Tröger's base diamine: Effect of bicyclic bridge on gas transport properties

    KAUST Repository

    Abdulhamid, Mahmoud A.

    2017-10-12

    A newly designed carbocyclic pseudo Tröger\\'s base diamine (CTB) monomer, 2,8-dimethyl-3,9-diamino-5,6,11,12-tetrahydro-5,11-methanodibenzo[a,e][8]annulene (CTBDA) and its isomeric analogue 2,8-dimethyl-(1,7)(4,10)(3,9)-diamino-5,6,11,12-tetrahydro-5,11-methanodibenzo[a,e][8]annulene (iCTBDA), were designed for the synthesis of microporous 6FDA-based polyimides (6FDA-CTBDA and 6FDA-iCTBDA). Both polyimides were soluble, exhibited excellent thermal stability of ∼490 °C, and had high surface areas of 587 m2 g−1 (6FDA-CTBDA) and 562 m2 g−1 (6FDA-iCTBDA). A 6FDA-based polyimide derived from 4,10-dimethyl-3,9-diamino-6H,12H-5,11-methanodibenzo[b,f][1,5]-diazocine (6FDA-TBDA) was made for comparison to investigate the effects of the basic tertiary nitrogen functionality in the Tröger\\'s base diamine on the polymer properties relative to the carbocyclic 6FDA-CTBDA analogue. 6FDA-TBDA displayed lower gas permeabilities but moderately higher gas-pair permselectivities than 6FDA-CTBDA. The enhanced permselectivity of 6FDA-TBDA resulted exclusively from higher diffusion-based selectivity. Direct gas sorption measurements demonstrated that the basicity in the Tröger\\'s base bridge moiety enhanced the sorption capacity of CO2 only slightly and had no effect on the CO2/CH4 solubility selectivity in 6FDA-TBDA vs. 6FDA-CTBDA.

  12. In silico toxicology models and databases as FDA Critical Path Initiative toolkits.

    Science.gov (United States)

    Valerio, Luis G

    2011-03-01

    In silico toxicology methods are practical, evidence-based and high throughput, with varying accuracy. In silico approaches are of keen interest, not only to scientists in the private sector and to academic researchers worldwide, but also to the public. They are being increasingly evaluated and applied by regulators. Although there are foreseeable beneficial aspects--including maximising use of prior test data and the potential for minimising animal use for future toxicity testing--the primary use of in silico toxicology methods in the pharmaceutical sciences are as decision support information. It is possible for in silico toxicology methods to complement and strengthen the evidence for certain regulatory review processes, and to enhance risk management by supporting a more informed decision regarding priority setting for additional toxicological testing in research and product development. There are also several challenges with these continually evolving methods which clearly must be considered. This mini-review describes in silico methods that have been researched as Critical Path Initiative toolkits for predicting toxicities early in drug development based on prior knowledge derived from preclinical and clinical data at the US Food and Drug Administration, Center for Drug Evaluation and Research.

  13. An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Qiu Ying Lau

    2015-10-01

    Full Text Available The lack of new antibacterial drugs entering the market and their misuse have resulted in the emergence of drug-resistant bacteria, posing a major health crisis worldwide. In particular, meticillin-resistant Staphylococcus aureus (MRSA, a pathogen responsible for numerous human infections, has become endemic in hospitals worldwide. Drug repurposing, the finding of new therapeutic indications for approved drugs, is deemed a plausible solution to accelerate drug discovery and development in this area. Towards this end, we screened 1163 drugs approved by the Food and Drug Administration (FDA for bioactivities against MRSA in a 10 μM single-point assay. After excluding known antibiotics and antiseptics, six compounds were identified and their MICs were determined against a panel of clinical MRSA strains. A toxicity assay using human keratinocytes was also conducted to gauge their potential for repurposing as topical agents for treating MRSA skin infections.

  14. Fabrication of 50-mg 252Cf neutron sources for the FDA [Food and Drug Administration] activation analysis facility

    International Nuclear Information System (INIS)

    Bigelow, J.E.; Cagle, E.B.; Knauer, J.B.

    1987-01-01

    The Transuranium Processing Plant (TPP) at ORNL has been requested by the Food and Drug Administration (FDA) to furnish 200 mg of 252 Cf for use in their new activation analysis facility. This paper discusses the procedure to be employed in fabricating the californium into four neutron sources, each containing a nominal 50-mg of 252 Cf. The ORNL Model LSD (Large, Stainless steel, Doubly encapsulated) neutron source consists of a 6.33-mm-diam aluminum pellet doubly encapsulated in Type 304L stainless steel. The pellet is comprised of an aluminum tube holding Cf 2 O 2 SO 4 microspheres confined by pressed aluminum powder. The microspheres are prepared in a separate vessel and then transferred into the specially designed aluminum tube prior to pressing

  15. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters

    Science.gov (United States)

    Kim, Hyosun

    2015-01-01

    Background: For the purpose of understanding the Food and Drug Administration’s (FDA’s) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. Methods: The FDA’s warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. Results: Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Conclusion: Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus

  16. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters

    Directory of Open Access Journals (Sweden)

    Hyosun Kim

    2015-12-01

    Full Text Available Background For the purpose of understanding the Food and Drug Administration’s (FDA’s concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs and warning letters issued by the FDA to pharmaceutical manufacturers. Methods The FDA’s warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014 regarding online promotional activities, were content-analyzed. Results Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Conclusion Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the

  17. Trends in utilization of smoking cessation agents before and after the passage of FDA boxed warning in the United States.

    Science.gov (United States)

    Shah, Drishti; Shah, Anuj; Tan, Xi; Sambamoorthi, Usha

    2017-08-01

    In 2009, the FDA required a black box warning (BBW) on bupropion and varenicline, the two commonly prescribed smoking cessation agents due to reports of adverse neuropsychiatric events. We investigated if there was a decline in use of bupropion and varenicline after the BBW by comparing the percent using these medications before and after BBW. We conducted a retrospective observational study using data from the Medical Expenditure Panel Survey from 2007 to 2014. The study sample consisted of adult smokers, who were advised by their physicians to quit smoking. We divided the time period into "pre-warning", "post-warning: immediate", and "post-warning: late." Unadjusted analysis using chi-square tests and adjusted analyses using logistic regressions were conducted to evaluate the change in bupropion and varenicline use before and after the BBW. Secondary analyses using piecewise regression were also conducted. On an average, 49.04% of smokers were advised by their physicians to quit smoking. We observed a statistically significant decline in varenicline use from 22.1% in year 2007 to 9.23% in 2014 (p valuesmoking by their physicians were less likely to use varenicline in the immediate post-BBW period as compared to pre-BBW period. While the use of varenicline continued to be significantly low in the late post-BBW period (AOR=0.45, 95% CI=0.31-0.64) as compared to the pre-BBW period, the trend in use as seen in piecewise regression remained stable (OR=0.90, 95% CI=0.75-1.06). We did not observe significant differences in bupropion use between the pre- and post-BBW periods. The passage of the FDA boxed warning was associated with a significant decline in the use of varenicline, but not in the use of bupropion. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. A Descriptive Longitudinal Study of Changes in Vape Shop Characteristics and Store Policies in Anticipation of the 2016 FDA Regulations of Tobacco Products, Including E-Cigarettes.

    Science.gov (United States)

    Yu, Sheila; Escobedo, Patricia; Garcia, Robert; Cruz, Tess Boley; Unger, Jennifer B; Baezconde-Garbanati, Lourdes; Meza, Leah; Sussman, Steve

    2018-02-11

    After proposing the "Deeming Rule" in 2014, the U.S. Food and Drug Administration (FDA) began regulating the manufacturing, marketing, and sales of electronic cigarette (e-cigarette) products as tobacco products in 2016. The current study conducted vape shop store observations and surveyed Los Angeles-area shop employees (assessing their beliefs, awareness, and perceptions of e-cigarettes and related FDA regulations) at two time points one year apart to better understand what vape shop retailers would do given FDA's soon-to-be-enacted Deeming Rule. The study also compared retailer beliefs/awareness/actions and store characteristics immediately after the Deeming Rule proposal versus a year after the Rule had been proposed, right before its enactment. Two data collection waves occurred before the Deeming Rule enactment, with Year 1 surveying 77 shops (2014) and Year 2 surveying 61 shops (2015-2016). Between the data collection points, 16 shops had closed. Among the shops that were open at both time points, the majority (95% in Year 1; 74% in Year 2) were aware of some FDA regulations or other policies applying to vape shops. However, overall awareness of FDA regulations and state/local policies governing e-cigarettes significantly decreased from Year 1 to Year 2. At both time points, all shops offered customers free puffs of nicotine-containing e-liquids (prohibited by the then upcoming Deeming Rule). Perceptions of e-cigarette safety also significantly decreased between the years. Exploring vape shop retailer perceptions and store policies (i.e., free puffs/samples displays, perceptions of e-cigarette safety, etc.) over time will help the FDA assess the needs of the vape shop community and develop more effective retailer education campaigns and materials targeted to increase compliance with the newly enacted regulations.

  19. Early Use of 60 Hz Frequency Subthalamic Stimulation in Parkinson's Disease: A Case Series and Review.

    Science.gov (United States)

    Ramdhani, Ritesh A; Patel, Amar; Swope, David; Kopell, Brian H

    2015-12-01

    Deep brain stimulation (DBS) is effective in treating the segmental symptoms of Parkinson's disease (PD) as well as axial symptoms that are levodopa responsive. PD patients on chronic DBS who develop axial symptoms and gait disturbances several years later oftentimes are refractory to high frequency stimulation (HFS). Several studies report benefit produced by low frequency subthalamic nucleus (STN) stimulation in such patients, though the sustainability of the effects has been mixed. To report the clinical outcomes of a series of patients with Parkinson's disease and levodopa responsive axial and gait disturbances who were switched to 60 Hz stimulation within one year of their DBS surgery. A retrospective review of 5 patients, whose severe pre-DBS, levodopa responsive gait disorders worsened on HFS STN-DBS and were subsequently switched to 60 Hz stimulation within 1 year of their surgery. The median age of this cohort was 66 years with median disease duration of 14 years. Four of 5 patients' experienced acute worsening of their axial and gait UPDRS III scores on HFS. All patients' gait disorder improved with 60 Hz along with amelioration of their segmental symptoms and reduction of their levodopa induced dyskinesia. The median time on HFS prior to switching to 60 Hz was two months. Stimulation through the ventral contacts was utilized in all patients with relatively modest changes achieved in levodopa equivalent daily dose. This case series demonstrates the clinical efficacy of utilizing low frequency (60 Hz) STN stimulation early in the DBS programming course in more advanced PD patients with levodopa responsive gait disturbance and freezing of gait. Activation of a broader stimulation field likely contributed to both axial and segmental symptom improvement while possibly aiding in the reduction of dyskinesia. © 2015 International Neuromodulation Society.

  20. Why did the FDA approve efavirenz 800 mg when co-administered with rifampin?

    Science.gov (United States)

    Liu, Jiang; Chan-Tack, Kirk M; Jadhav, Pravin; Seo, Shirley; Robertson, Sarah M; Kraft, Jeffrey; Singer, Mary E; Struble, Kimberly A; Arya, Vikram

    2014-06-01

    Literature reports regarding the efficacy of efavirenz (EFV) 600 mg with rifampin (RIF) are not consistent. Evaluation of a drug-drug interaction (DDI) study and supportive semi-mechanistic population pharmacokinetic (PK) analyses were undertaken to help delineate this issue. DDI study and supportive semi-mechanistic population PK analyses were provided by BMS. Population PK analysis was based on six studies with intensive EFV PK sampling. An ACTG study with sparse PK sampling was used for model evaluation. Simulations compared EFV exposure at various doses in combination with RIF to EFV exposures at 600 mg once daily (QD). Effects of CYP2B6 genotypes on the magnitude of EFV-RIF interaction were also explored. In DDI study, co-administering EFV 600 mg QD and RIF reduced mean EFV exposure by ~ 30%. Population PK model provided acceptable predictive performance of central tendency and variability for EFV C0, Cmax, and AUC. Simulations predicted that increasing EFV to 800 mg QD with RIF would result in EFV AUC and Cmax similar to EFV 600 mg QD alone. EFV AUC and Cmax were ~ 2 times higher in subjects with reduced function CYP2B6 genotypes. However, the RIF effect was consistent across all genotypes. EFV dose adjustment to 800 mg QD did not increase the risk of overexposure compared to 600 mg EFV QD within each genotype. Dose adjustment based on matching systemic exposure was recommended to mitigate the potential for sub-therapeutic EFV exposures. Our review did not reveal any safety concerns in subjects receiving EFV 800 mg QD with RIF.

  1. Missed Opportunities in the Patient-Focused Drug Development Public Meeting and Scientific Workshop on Female Sexual Dysfunction Held at the FDA, October 2014

    NARCIS (Netherlands)

    Tiefer, Leonore; Laan, Ellen; Basson, Rosemary

    2015-01-01

    There were numerous missed opportunities at the October 2014 U.S. Food and Drug Administration (FDA) meeting on female sexual dysfunction (FSD). They included opportunities to hear from a diverse range of patients and to engage in evidence-based discussions of unmet medical needs, diagnostic

  2. A dual track system to give more-rapid access to new drugs: applying a systems mindset to the US food and drug administration (FDA).

    Science.gov (United States)

    Madden, Bartley J

    2009-02-01

    A widely applicable lesson learned from systems analysis is that a proposed change should always be studied in terms of value to the customer and not a gain in efficiency of any particular component of the system. A systems mindset reveals invalid assumptions that have caused the FDA to substitute its own needs for the needs of its customers (patients). Further, the key constraint to overall system improvement is the lack of consumer choice and competition due to FDA's monopoly over access to drugs. Therefore, we need legislation to implement a proposed dual track system for access to drugs that have successfully passed Phase I safety trials. On one track, an experimental drug would continue with conventional FDA clinical trials. On a new, free-to-choose track, patients, advised by their doctors, would make informed decisions about immediate access to not-yet-approved drugs. Internet access to a government-operated tradeoff evaluation database would provide patients and doctors with up-to-date information on all drug treatment outcomes for both tracks. Dual tracking is a dynamic process that overcomes the limitations of a static FDA regulatory process that ignores individual risk preferences.

  3. Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard.

    Science.gov (United States)

    Ting, Tricia Y; Jiang, Wenlei; Lionberger, Robert; Wong, Jessica; Jones, Jace W; Kane, Maureen A; Krumholz, Allan; Temple, Robert; Polli, James E

    2015-09-01

    To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs

  4. Community Pharmacists’ Classification of Prescription Drugs into an Expanded Class of Nonprescription Drugs under the FDA's Proposed NSURE Initiative

    Directory of Open Access Journals (Sweden)

    Ruchitbhai M. Shah

    2017-10-01

    Full Text Available Objectives: There has been considerable debate over the last few decades about creating a third class of drugs that would not require a prescription or not be available freely over the counter, but require a pharmacist’s consultation upon purchase. These debates reignited again in 2012, when the Food and Drug Administration (FDA held a hearing about a third class of drugs positioned as an expanded nonprescription drug class under the FDAs Nonprescription Safe-Use Regulatory Expansion (NSURE Initiative. The objective of this study was to determine which prescription drugs community pharmacists believe are acceptable additions to an expanded definition of nonprescription drugs that would be available pending pharmacists’ consultation with a patient. Methods: This cross-sectional study was conducted using a self-report, web-based survey administered to a national panel of community pharmacists. The survey contained a list of 24 current “prescription-only” drugs which may be potential candidates for an expanded nonprescription drug class, based on criteria outlined by the FDA, and questions related to respondent demographic and practice characteristics. The respondents were asked to indicate whether a particular drug should be marketed as a prescription drug, nonprescription drug or as part of an expanded non-prescription drug class. Descriptive analyses were conducted to determine the drugs that community pharmacists believed would be suitable additions to an expanded non-prescription drug class under the NSURE initiative. Results: 462 completed surveys were received. Most respondents indicated that clopidogrel bisulfate (85.3% and zolpidem (86.6% should continue to be dispensed as prescription drugs. Atorvastatin, metformin, and sildenafil (among others were considered appropriate to be marketed as an expanded nonprescription drug, in other words, dispensed without a prescription but upon pharmacist consultation. Desloratadine (64.6% and

  5. Trends in internet search activity, media coverage, and patient-centered health information after the FDA safety communications on surgical mesh for pelvic organ prolapse.

    Science.gov (United States)

    Stone, Benjamin V; Forde, James C; Levit, Valerie B; Lee, Richard K; Te, Alexis E; Chughtai, Bilal

    2016-11-01

    In July 2011, the US Food and Drug Administration (FDA) issued a safety communication regarding serious complications associated with surgical mesh for pelvic organ prolapse, prompting increased media and public attention. This study sought to analyze internet search activity and news article volume after this FDA warning and to evaluate the quality of websites providing patient-centered information. Google Trends™ was utilized to evaluate search engine trends for the term "pelvic organ prolapse" and associated terms between 1 January 2004 and 31 December 2014. Google News™ was utilized to quantify the number of news articles annually under the term "pelvic organ prolapse." The search results for the term "pelvic organ prolapse" were assessed for quality using the Health On the Net Foundation (HON) certification. There was a significant increase in search activity from 37.42 in 2010 to 57.75 in 2011, at the time of the FDA communication (p = 0.021). No other annual interval had a statistically significant increase in search activity. The single highest monthly search activity, given the value of 100, was August 2011, immediately following the July 2011 notification, with the next highest value being 98 in July 2011. Linear regression analysis of news articles per year since the FDA communication revealed r 2  = 0.88, with a coefficient of 186. Quality assessment demonstrated that 42 % of websites were HON-certified, with .gov sites providing the highest quality information. Although the 2011 FDA safety communication on surgical mesh was associated with increased public and media attention, the quality of relevant health information on the internet remains of poor quality. Future quality assurance measures may be critical in enabling patients to play active roles in their own healthcare.

  6. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  7. A Descriptive Longitudinal Study of Changes in Vape Shop Characteristics and Store Policies in Anticipation of the 2016 FDA Regulations of Tobacco Products, Including E-Cigarettes

    Directory of Open Access Journals (Sweden)

    Sheila Yu

    2018-02-01

    Full Text Available After proposing the “Deeming Rule” in 2014, the U.S. Food and Drug Administration (FDA began regulating the manufacturing, marketing, and sales of electronic cigarette (e-cigarette products as tobacco products in 2016. The current study conducted vape shop store observations and surveyed Los Angeles–area shop employees (assessing their beliefs, awareness, and perceptions of e-cigarettes and related FDA regulations at two time points one year apart to better understand what vape shop retailers would do given FDA’s soon-to-be-enacted Deeming Rule. The study also compared retailer beliefs/awareness/actions and store characteristics immediately after the Deeming Rule proposal versus a year after the Rule had been proposed, right before its enactment. Two data collection waves occurred before the Deeming Rule enactment, with Year 1 surveying 77 shops (2014 and Year 2 surveying 61 shops (2015–2016. Between the data collection points, 16 shops had closed. Among the shops that were open at both time points, the majority (95% in Year 1; 74% in Year 2 were aware of some FDA regulations or other policies applying to vape shops. However, overall awareness of FDA regulations and state/local policies governing e-cigarettes significantly decreased from Year 1 to Year 2. At both time points, all shops offered customers free puffs of nicotine-containing e-liquids (prohibited by the then upcoming Deeming Rule. Perceptions of e-cigarette safety also significantly decreased between the years. Exploring vape shop retailer perceptions and store policies (i.e., free puffs/samples displays, perceptions of e-cigarette safety, etc. over time will help the FDA assess the needs of the vape shop community and develop more effective retailer education campaigns and materials targeted to increase compliance with the newly enacted regulations.

  8. Petitioning the FDA to Improve Pharmaceutical, Device and Public Health Safety by Ordinary Citizens: A Descriptive Analysis.

    Science.gov (United States)

    Chen, Brian K; Yang, Y Tony; Cheng, Xi; Bian, John; Bennett, Charles L

    2016-01-01

    The United States Constitution protects the right of citizens to petition the government for "a redress of grievances." This right has important implications for citizens desiring to advance the public health by petitioning administrative agencies, such as the Food and Drug Administration, to take safety actions. We examined a total of 1,915 petitions filed between 2001 and 2013 to investigate the outcomes of citizen petitions that address public health concerns. We found that most petitions were filed by manufacturers against other manufacturers. Only 346 (18%) of all petitions were submitted by individuals and non-profit organizations, and 178 (87.3%) of these petitions with a final response were denied. On average, these petitions required 2.85 years for a final agency decision, and many decisions remain pending 10-13 years after their initial submission. The great majority of the approved requests included some form of risk communication, such as labeling changes, boxed warnings or placement of a drug into a Risk Evaluation and Mitigation Strategy. As a policy instrument to improve the safety of medical and food products, the citizen petition process requires sophisticated legal and scientific expertise, and may not represent a viable route for ordinary citizens to petition the FDA to "redress grievances."

  9. FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.

    Science.gov (United States)

    Musdal, Yaman; Hegazy, Usama M; Aksoy, Yasemin; Mannervik, Bengt

    2013-09-05

    Glutathione transferase P1-1 (GST P1-1) is often overexpressed in tumor cells and is regarded as a contributor to their drug resistance. Inhibitors of GST P1-1 are expected to counteract drug resistance and may therefore serve as adjuvants in the chemotherapy of cancer by increasing the efficacy of cytostatic drugs. Finding useful inhibitors among compounds used for other indications would be a shortcut to clinical applications and a search for GST P1-1 inhibitors among approved drugs and other compounds was therefore conducted. We tested 1040 FDA-approved compounds as inhibitors of the catalytic activity of purified human GST P1-1 in vitro. We identified chlorophyllide, merbromine, hexachlorophene, and ethacrynic acid as the most effective GST P1-1 inhibitors with IC50 values in the low micromolar range. For comparison, these compounds were even more potent in the inhibition of human GST A3-3, an enzyme implicated in steroid hormone biosynthesis. In distinction from the other inhibitors, which showed conventional inhibition patterns, the competitive inhibitor ethacrynic acid elicited strong kinetic cooperativity in the glutathione saturation of GST P1-1. Apparently, ethacrynic acid serves as an allosteric inhibitor of the enzyme. In their own right, the compounds investigated are less potent than desired for adjuvants in cancer chemotherapy, but the structures of the most potent inhibitors could serve as leads for the synthesis of more efficient adjuvants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Gas separation performance of carbon molecular sieve membranes based on 6FDA-mPDA/DABA (3:2) polyimide.

    Science.gov (United States)

    Qiu, Wulin; Zhang, Kuang; Li, Fuyue Stephanie; Zhang, Ke; Koros, William J

    2014-04-01

    6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO2 /CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2 /CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO2 /CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2 /CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Derivative emission spectrofluorimetry: Application to the analysis of newly approved FDA combination of ibuprofen and famotidine in tablets.

    Science.gov (United States)

    Ragab, Marwa A A; El-Kimary, Eman I

    2015-09-01

    A new combination of ibuprofen (NSAID) and famotidine (H2 receptor antagonist) was recently approved by the FDA. It was formulated to relief pain while decreasing the risk of ulceration, which is a common problem for patients receiving NSAID. A rapid and simple derivative emission spectrofluorimetric method is proposed for the simultaneous analysis of this combination in their pharmaceutical preparation. The method is based upon measurement of the native fluorescence intensity of the two drugs at λex = 233 nm in acetonitrile. The emission data were differentiated using the first (D1) derivative technique. The plots of derivative fluorescence intensity versus concentration were rectilinear over a range of 2-35 and 0.4-8 µg/mL for both ibuprofen (IBU) and famotidine (FAM), respectively. The method was sensitive as the limits of detection were 0.51 and 0.12 µg/mL and limits of quantitation were 1.70 and 0.39 µg/mL, for IBU and FAM respectively. The proposed derivative emission spectrofluorimetric method was successfully applied for the determination of the two drugs in their synthetic mixtures and tablets with good accuracy and precision. The proposed method was validated as per ICH guidelines. Copyright © 2014 John Wiley & Sons, Ltd.

  12. FDA's expanding postmarket authority to monitor and publicize food and consumer health product risks: the need for procedural safeguards to reduce "transparency" policy harms in the post-9/11 regulatory environment.

    Science.gov (United States)

    Roller, Sarah Taylor; Pippins, Raqiyyah R; Ngai, Jennifer W

    2009-01-01

    This article provides a summary of the expansion of FDA's discretionary authority in the post-9/11 period, particularly with respect to FDA's authority to monitor and publicize potential health risks linked to food, dietary supplements, nonprescription drugs, and other consumer health products. In addition, this article evaluates the need for FDA to establish procedural safeguards to reduce the significant risks of unintended and undue harm to people and regulated companies that can result from adverse publicity in the more "transparent" post 9/11 FDA regulatory environment. Specifically, Part I summarizes the amendments to the FDCA enacted during the post-9/11 period that have expanded FDA's postmarket authority to monitor, evaluate, and publicize potential health risks linked to food, dietary supplements, nonprescription drugs and other consumer health products marketed in the United States, in conjunction with FDA's Sentinel Initiative, Reportable Food Registry, and other adverse event reporting requirements. Part II discusses the convergence of FDA's expanded postmarket authority to publicize product-related risks with President Obama's transparency initiative aimed at fostering "open government" through increased public access to government information. In addition, Part II considers the nature of the procedural safeguards needed in the post-9/11 FDA regulatory environment, in view of FDA's historical record and illustrative cases that help expose how adverse "transparency" surrounding FDA warning letters, recalls and safety alerts concerning products in the marketplace can have undue and unintended prejudicial and harmful effects for the people and companies that are legally responsible for such products. Finally, based on these analysis, this article concludes with some observations concerning the nature of the procedural safeguards needed to reduce the significant risks of "transparency" policy harms in the pos-9/11 regulatory environment.

  13. 21 CFR 822.16 - What will you consider in the review of my submission?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What will you consider in the review of my submission? 822.16 Section 822.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE FDA Review and Action § 822.16 What will you...

  14. 75 FR 30033 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2010-05-28

    ...] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment... submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork... intentionally contaminate the food supply would be deterred from entering the food production chain. Two, if FDA...

  15. FDA Online Label Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The drug labels and other drug-specific information on this Web site represent the most recent drug listing information companies have submitted to the Food and Drug...

  16. Recent FDA Regulatory Measures

    NARCIS (Netherlands)

    Grossman, M.R.

    2014-01-01

    The use of antimicrobial drugs (antibiotics) in animal feed or drinking water helps animals to gain weight more efficiently, but also contributes to antimicrobial resistance, which makes important antibiotics less effective and threatens public health.

  17. FDA 101: Dietary Supplements

    Science.gov (United States)

    ... and include among others vitamin and mineral products "botanical" or herbal products—These come in many forms and may include plant materials, algae, macroscopic fungi, or a combination of these materials. ...

  18. Statins and interstitial lung disease: a systematic review of the literature and of food and drug administration adverse event reports.

    Science.gov (United States)

    Fernández, Antonio B; Karas, Richard H; Alsheikh-Ali, Alawi A; Thompson, Paul D

    2008-10-01

    To systematically review all published case reports and the US Food and Drug Administration adverse event reporting (FDA-AER) database to examine the relationship between statins and interstitial lung disease (ILD). PubMed (1987 to September 2007) and the FDA-AER database (as of June 2007) were searched for reports of ILD in which a statin was listed as a causative suspect. Two authors (one author for Pub Med cases and one for FDA-AER cases) independently abstracted patient data. Given the paucity of information, all case reports and case series in English and French were included. All adverse event reports from the FDA-AER database in which a statin was listed as causative suspect were included. The literature search using PubMed yielded eight articles describing a total of 14 case reports of ILD in association with statin use. The FDA-AER system database contained 162 cases of reported statin-induced ILD as of June 2007. For every 10,000 reports of a statin-associated adverse event, approximately 1 to 40 reports were for ILD. Statin-induced ILD is a possible newly recognized side effect of statin therapy. The mechanism of lung injury is not defined. The current review provides novel information from the FDA-AER that supports a possible, although unusual, pulmonary class effect of statins.

  19. Moulds associated with contaminated ocular and injectable drugs: FDA recalls, epidemiology considerations, drug shortages, and aseptic processing.

    Science.gov (United States)

    Ahearn, Donald G; Stulting, R Doyle

    2017-10-09

    Recent (2012) grave but rare outbreaks of fungal meningitis and endophthalmitis associated with drugs contaminated with select environmental moulds (Exserohilum and Fusarium, respectively) have exacerbated mycology concerns for formulation, good laboratory practices (GLP), and use of the final drug product. Intensified investigations (2013-2015) by the Food and Drug Administration (FDA) that included added responsibilities for specialty compounding laboratories have prompted at least nine voluntary mould-related drug recalls during 2014-2015. Both primary manufactures (five recalls, two companies) and secondary-processing compound laboratories (at least eight recalls, six companies) and near 0.8 million units were involved. These constituted minor fractions of recalled drug products in an estimated 2500 recalls among other causes during this time period. Recalls of similar drugs in 2016 were indirectly related to fungi. None of the mould-related- drug-recall episodes during 2014-2016 have been identified with fungal disease outbreaks. The recalls included drugs in short supply worldwide such as injectable sodium chloride- and related saline solutions as well as ocular formulations. Insufficient environmental monitoring and GLP compliance, particularly for aseptic processing of non-preserved formulations, appeared to be underlying factors in the fungal contaminations. Observations of mould growth in drugs during their processing should be accurately recorded and investigated; cryptic listings under "particulate" designations should be avoided. Confirmed identifications for chronic contaminants are recommended. Heat-tolerant moulds with resistant morphotypes are prime concerns. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Use of FDA approved medications for Alzheimer's disease in mild dementia is associated with reduced informal costs of care.

    Science.gov (United States)

    Behrens, Stephanie; Rattinger, Gail B; Schwartz, Sarah; Matyi, Joshua; Sanders, Chelsea; DeBerard, M Scott; Lyketsos, Constantine G; Tschanz, JoAnn T

    2018-03-21

    The use of FDA approved medications for Alzheimer's disease [AD; FDAAMAD; (cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists)] has been associated with symptomatic benefit with a reduction in formal (paid services) and total costs of care (formal and informal costs). We examined the use of these medications and their association with informal costs in persons with dementia. Two hundred eighty participants (53% female, 72% AD) from the longitudinal, population-based Dementia Progression Study in Cache County, Utah (USA) were followed up to ten years. Mean (SD) age at baseline was 85.6 (5.5) years. Informal costs (expressed in 2015 dollars) were calculated using the replacement cost method (hours of care multiplied by the median wage in Utah in the visit year) and adjusted for inflation using the Medical Consumer Price Index. Generalized Estimating Equations with a gamma log-link function were used to examine the longitudinal association between use of FDAAMAD and informal costs. The daily informal cost for each participant at baseline ranged from $0 to $318.12, with the sample median of $9.40. Within the entire sample, use of FDAAMAD was not significantly associated with informal costs (expβ = 0.73, p = 0.060). In analyses restricted to participants with mild dementia at baseline (N = 222), use of FDAAMAD was associated with 32% lower costs (expβ = 0.68, p = 0.038). Use of FDAAMAD was associated with lower informal care costs in those with mild dementia only.

  1. Gas Separation Performance of Carbon Molecular Sieve Membranes Based on 6FDA-mPDA/DABA (3:2) Polyimide

    KAUST Repository

    Qiu, Wulin

    2014-02-23

    6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO 2/CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2/CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO 2/CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2/CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. Permeating through: Polyimide-based uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes are prepared. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes are discussed in relation to pyrolysis protocols. Both the polymer and CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.

    Science.gov (United States)

    Suzuki, Yukiya; Suzuki, Honami; Umetsu, Ryogo; Uranishi, Hiroaki; Abe, Junko; Nishibata, Yuri; Sekiya, Yasuaki; Miyamura, Nobuteru; Hara, Hideaki; Tsuchiya, Teruo; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2015-01-01

    Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.

  3. Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011.

    Science.gov (United States)

    Rathi, Vinay K; Krumholz, Harlan M; Masoudi, Frederick A; Ross, Joseph S

    2015-08-11

    The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer

  4. The FDA guidance on therapeutic cancer vaccines: the need for revision to include preventive cancer vaccines or for a new guidance dedicated to them.

    Science.gov (United States)

    Finn, Olivera J; Khleif, Samir N; Herberman, Ronald B

    2015-11-01

    Cancer vaccines based on antigens derived from self molecules rather than pathogens have been under basic and clinical investigations for many years. Up until very recently, they had been tested primarily in the setting of metastatic disease with the goal to engage the immune system in slowing down disease progression. Many therapeutic vaccine trials, either investigator initiated or led by pharmaceutical companies, have been completed and many are currently ongoing, following the FDA Guidance on therapeutic cancer vaccines published in 2011. In recent years, the target of cancer vaccines is being shifted to early cancer and even premalignant disease with the goal of preventing cancer. Although some issues addressed in the FDA Guidance on therapeutic vaccines apply to preventive vaccines, many do not. Here, we discuss a set of recommendations for revising the current Guidance to also cover preventive vaccines, or to include in a new Guidance dedicated specifically to vaccines for cancer prevention. ©2015 American Association for Cancer Research.

  5. Fabrication of 6FDA-durene membrane incorporated with zeolite T and aminosilane grafted zeolite T for CO2/CH4 separation

    Science.gov (United States)

    Jusoh, Norwahyu; Fong Yeong, Yin; Keong Lau, Kok; Shariff, Azmi Mohd

    2017-08-01

    In the present work, zeolite T and aminosilane grafted zeolite T are embedded into 6FDA-durene polyimide phase for the fabrication of mixed matrix membranes (MMMs). FESEM images demonstrated that the improvement of interfacial adhesion between zeolite and polymer phases in MMM loaded with aminosilane grafted zeolite T was not significant as compared to zeolite T/6FDA-durene MMM. From the gas permeation test, CO2/CH4 selectivity up to 26.4 was achieved using MMM containing aminosilane grafted zeolite T, while MMM loaded with ungrafted zeolite T showed CO2/CH4 selectivity of 19.1. In addition, MMM incorporated with aminosilane grafted zeolite T particles successfully lies on Robeson upper bound 2008, which makes it an attractive candidate for CO2/CH4 separation.

  6. FDA's proposed rules on patent listing requirements for new drug and 30-month stays on ANDA approval (proposed Oct. 24, 2002).

    Science.gov (United States)

    Hui, Yuk Fung

    2003-01-01

    In order to close the loophole in the generic drug approval process that allows a brand name drug patent holder to delay or defeat generic drug application merely by technicality, the FDA recently proposed to modify its regulations. Those proposals affect the patent listing requirements of a new drug application, and the duration of time that a generic drug application could be put on hold in the event of a patent infringement suit. With the modified rules, the FDA expects to see an increase in the availability of generic drugs, which eventually will lead to lower drug costs. Ms. Hui discusses the contents of the proposed regulations and provides an analysis of the proposed rule's legal authority, implications on patent rights, and impact on the pharmaceutical industry.

  7. The Conundrum of Online Prescription Drug Promotion Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Wanasika, Isaac

    2016-03-26

    This commentary discusses pertinent issues from Hyosun Kim's paper on online prescription drug promotion. The study is well-designed and the findings highlight some of the consequences of the Food and Drug Administration's (FDA's) decision to deregulate online advertising of prescription drugs. While Kim's findings confirm some of the early concerns, they also provide a perspective of implementation challenges in the ever-changing technological environment. © 2016 by Kerman University of Medical Sciences.

  8. Bureau of Radiological Health...a look at Food and Drug Administration's (FDA's) program to protect the American consumer from radiaton. Final report

    International Nuclear Information System (INIS)

    Eccleston, R.C.; Barnett, M.H.

    1977-04-01

    The report provides a brief overview of the FDA's major regulatory and voluntary efforts in the area of radiation control, and examines the impact of the Agency's programs to eliminate unproductive radiation exposure to the American consumer. It concludes with a summary of present and future concerns about newly emerging radiation-emitting products and uses, and the potential public health problems which they may engender

  9. Do FDA label changes work? Assessment of the 2010 class label change for proton pump inhibitors using the Sentinel System's analytic tools.

    Science.gov (United States)

    Sobel, Rachel E; Bate, Andrew; Marshall, James; Haynes, Kevin; Selvam, Nandini; Nair, Vinit; Daniel, Gregory; Brown, Jeffrey S; Reynolds, Robert F

    2018-03-01

    To pilot use of the US Food and Drug Administration's (FDA's) Sentinel System data and analytic tools by a non-FDA stakeholder through the Innovation in Medical Evidence Development and Surveillance system of the Reagan Udall Foundation. We evaluated the US FDA 2010 proton pump inhibitor (PPI) class label change that warned of increased risk of bone fracture, to use PPIs for the lowest dose and shortest duration, and to manage bone status for those at risk for osteoporosis. The cohort consisted of adults aged 18 years or older prescribed PPIs without fracture risk factors. We evaluated incident and prevalent uses of the 8 PPIs noted in the label change. Outcomes evaluated before and after label change were PPI dispensing patterns, incident fractures, and osteoporosis screening or interventions. Consistent with FDA use of descriptive tools, we did not include direct comparisons or statistical testing. There were 1 488 869 and 2 224 420 incident PPI users in the before [PRE] and after [POST] periods, respectively. Users with 1 year or more of exposure decreased (8.4% vs 7.5%), as did mean days supplied/user (130.4 to 113.7 d among all users and 830.8 to 645.4 d among users with 1 y or more of exposure). Osteoporosis screening and interventions did not appear to increase, but the proportion of patients with fractures decreased (4.4% vs 3.1%). Prevalent user results were similar. This analysis demonstrated the ability to use Sentinel tools to assess the effectiveness of a label change and accompanying communication at the population level and suggests an influence on subsequent dispensing behavior. Copyright © 2018 John Wiley & Sons, Ltd.

  10. How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers' views.

    Science.gov (United States)

    Tafuri, G; Stolk, P; Trotta, F; Putzeist, M; Leufkens, H G; Laing, R O; De Allegri, M

    2014-01-01

    The process leading to a regulatory outcome is guided by factors both related and unrelated to the data package, defined in this analysis as 'formal and informal factors', respectively. The aim of this qualitative study was to analyse which formal and informal factors drive the decision-making process of the European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulators with regard to anticancer drugs, using in-depth semi-structured interviews with regulators of the two agencies. In line with the theory and practice of qualitative research, no set sample size was defined a priori. Respondent enrolment continued until saturation and redundancy were reached. Data were collected through means of in-depth semi-structured interviews conducted either in a face-to-face setting or via Skype(®) with each regulator. The interviews were audio-recorded and verbatim transcribed. The analysis was manually carried out on the transcribed text. Data were independently coded and categorized by two researchers. Interpretation of the findings emerged through a process of triangulation between the two. Seven EMA and six FDA regulators, who had extensive experience with making decisions about anticancer medicines, were interviewed between April and June 2012. There is an open dialogue between the FDA and EMA, with the two moving closer and exchanging information, not opinions. Differences in decision-making between the agencies may be due to a different evaluation of end points. Different interaction modalities with industry and patients represent an additional source of divergence with a potential impact on decision-making. The key message of our respondents was that the agencies manage uncertainty in a different way: unlike the EMA, the FDA has a prevailing attitude to take risks in order to guarantee quicker access to new treatments. Although formal factors are the main drivers for regulatory decisions, the influence of informal factors plays an important role in

  11. Procedural trends, outcomes, and readmission rates pre-and post-FDA approval for MitraClip from the National Readmission Database (2013-14).

    Science.gov (United States)

    Panaich, Sidakpal S; Arora, Shilpkumar; Badheka, Apurva; Kumar, Varun; Maor, Elad; Raphael, Claire; Deshmukh, Abhishek; Reeder, Guy; Eleid, Mackram; Rihal, Charanjit S

    2017-11-20

    There are sparse clinical data on the procedural trends, outcomes and readmission rates following FDA approval and expansion of Transcatheter mitral valve repair/MitraClip ® . Whether a complex new technology can be disseminated safely and quickly is controversial. The study cohort was derived from the National Readmission Data (NRD) 2013-14. MitraClip ® was identified using appropriate International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. The primary outcome was a composite of in-hospital mortality + procedural complications. Secondary outcome included 30-day readmissions. Hierarchical two level logistic models were used to evaluate study outcomes. Our analysis included 2003 MitraClip ® procedures. Overall in-hospital mortality was 3.9%. As expected, there was a significant increase in procedural volume post-FDA approval. Importantly, a corresponding downward trend in mortality and procedural complications was observed. Significant predictors of in-hospital mortality and procedural complications included the use of vasopressors (P procedures had lower in-hospital mortality (P procedures. A significant increase in MitraClip ® procedural volumes occurred post-FDA approval. Overall morbidity and mortality were low and trended downwards. Hospital procedure volume ≥10 cases were associated with lower mortality and overall complication rates. These data suggest a successful roll out of a very complex novel structural heart procedure. © 2017 Wiley Periodicals, Inc.

  12. Novel 6FDA-based polyimides derived from sterically hindered Tröger's base diamines: Synthesis and gas permeation properties

    KAUST Repository

    Ghanem, Bader

    2016-04-30

    Two novel Tröger\\'s base-based di-o-substituted diamine monomers were synthesized and used to prepare two intrinsically microporous 6FDA-based polyimides (PIM-PI-TB-1 and PIM-PI-TB-2) with high molecular weight, high thermal stability and excellent solubility in common organic solvents. Compared to previously reported methods for preparing TB-based diamines, which are based on reduction of dimerized nitro-substituted anilines or condensation of phenylenediamine derivatives with dianhydrides, the novel protocol can be used to prepare different functionalized TB-based diamine monomers from a wide variety of aniline derivatives. PIM-PI-TB-1 (made from 6FDA and dibromo-tetramethyl-substituted TB diamine) and PIM-PI-TB-2 (made from 6FDA and tetramethyl-substituted TB diamine) are intrinsically microporous polymers with high BET surface areas of 440 m2/g and 580 m2/g, respectively. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 bar for fresh and 180 days aged films. Both TB-based polyimides exhibited high gas permeability with moderate selectivity. The gas permeability dropped significantly coupled with a moderate increase in selectivity after long-term physical aging of 180 days.

  13. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus [v1; ref status: indexed, http://f1000r.es/4qh

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2014-11-01

    Full Text Available We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35. When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

  14. Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System.

    Science.gov (United States)

    Raschi, E; Poluzzi, E; Koci, A; Antonazzo, I C; Marchesini, G; De Ponti, F

    2016-05-01

    We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders. HF during DPP4-I use was recorded in 390 reports (4.4% of total reports). In exploratory analysis, statistically significant ROR emerged for DPP-4-I as a class (ROR = 1.17; 95% CI = 1.05-1.29), saxagliptin (1.68; 1.29-2.17), vildagliptin (2.39; 1.38-4.14), and rosiglitazone (13.98; 13.30-14.70). In consolidated analyses, the ROR for saxagliptin (2.60; 1.92-3.50) and vildagliptin (4.07; 2.28-7.27) increased, and became also significant for sitagliptin (1.61; 1.40-1.86). Concomitant drugs were reported in more than 50% of cases; the adjusted RORs of saxagliptin (2.30; 1.70-3.10), vildagliptin (3.15; 1.76-5.63), and sitagliptin (1.48; 1.28-1.71) were nonetheless significant. FAERS data are consistent with clinical studies on a possible association between saxagliptin and HF. The disproportionate reporting of HF with sitagliptin, conflicting with a recent phase IV trial, suggests that cardiovascular safety requires close post-marketing vigilance by clinicians of individual DPP-4-I in the community until the issue of class effect is solved. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the

  15. Multilaboratory particle image velocimetry analysis of the FDA benchmark nozzle model to support validation of computational fluid dynamics simulations.

    Science.gov (United States)

    Hariharan, Prasanna; Giarra, Matthew; Reddy, Varun; Day, Steven W; Manning, Keefe B; Deutsch, Steven; Stewart, Sandy F C; Myers, Matthew R; Berman, Michael R; Burgreen, Greg W; Paterson, Eric G; Malinauskas, Richard A

    2011-04-01

    This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat)=500) and turbulent flow conditions (Re(throat)≥3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re(throat)=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available

  16. Review of Drug Quality and Security Act of 2013: The Drug Supply Chain Security Act (DSCSA

    Directory of Open Access Journals (Sweden)

    Elona Gjini

    2016-10-01

    Full Text Available The Drug Supply Chain Security Act (DSCSA signed into law in November 27, 2013 by president Obama creates a uniform national standard for tracing drug products through the supply chain. The goal of DQSA is to enhance FDA’s ability to help protect consumers by detecting and removing potential dangerous products from the pharmaceutics distribution supply chain. A new electronic, interoperable system will identify and trace only prescription drugs in the finished form for human use while distributed in the United States. The purpose of this review was to shed light on a complex and complicated process that it will require cooperation between FDA and drug manufactures, wholesale drug distributors, repackagers and dispensers. The implementation of the DSCSA is based on several law requirements and FDA has developed a schedule with time frames for each of them to be executed over a 10-year period. From this review, FDA recommendations are provided through the FDA Guidance on Identifying Suspect Product document to help trading partners and provide information about the risk of suspect drugs entering the supply chain. Moreover, FDA organized on April 5-6, 2016 in Silver Spring, MD a public workshop to gather valuable feedback from stakeholders who shared their input about the implementation of the new electronic system and its requirements. By the end of 2023, a unified system will provide easier data exchange and less errors, and will increase the safety and security of the pharmaceutical distribution supply chain.   Type: Student Project

  17. Considering the Future of Pharmaceutical Promotions in Social Media Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Carpentier, Francesca Renee Dillman

    2016-02-09

    This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim's article of the major themes in recent Food and Drug Administration (FDA) warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim's rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA's attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media. © 2016 by Kerman University of Medical Sciences.

  18. The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

    Science.gov (United States)

    Yazdanian, Mehran; Briggs, Katherine; Jankovsky, Corinne; Hawi, Amale

    2004-02-01

    The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in biorelevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0. and 7.4 relative to marketed dose strengths in 250 ml. The pKa values for the acidic NSAIDs studied were between 3.5 and 5.1. and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen. and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs

  19. Constructing the informatics and information technology foundations of a medical device evaluation system: a report from the FDA unique device identifier demonstration.

    Science.gov (United States)

    Drozda, Joseph P; Roach, James; Forsyth, Thomas; Helmering, Paul; Dummitt, Benjamin; Tcheng, James E

    2018-02-01

    The US Food and Drug Administration (FDA) has recognized the need to improve the tracking of medical device safety and performance, with implementation of Unique Device Identifiers (UDIs) in electronic health information as a key strategy. The FDA funded a demonstration by Mercy Health wherein prototype UDIs were incorporated into its electronic information systems. This report describes the demonstration's informatics architecture. Prototype UDIs for coronary stents were created and implemented across a series of information systems, resulting in UDI-associated data flow from manufacture through point of use to long-term follow-up, with barcode scanning linking clinical data with UDI-associated device attributes. A reference database containing device attributes and the UDI Research and Surveillance Database (UDIR) containing the linked clinical and device information were created, enabling longitudinal assessment of device performance. The demonstration included many stakeholders: multiple Mercy departments, manufacturers, health system partners, the FDA, professional societies, the National Cardiovascular Data Registry, and information system vendors. The resulting system of systems is described in detail, including entities, functions, linkage between the UDIR and proprietary systems using UDIs as the index key, data flow, roles and responsibilities of actors, and the UDIR data model. The demonstration provided proof of concept that UDIs can be incorporated into provider and enterprise electronic information systems and used as the index key to combine device and clinical data in a database useful for device evaluation. Keys to success and challenges to achieving this goal were identified. Fundamental informatics principles were central to accomplishing the system of systems model. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2014-01-15

    Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance.

  1. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2015-11-01

    Full Text Available Olayide A Arodola, Mahmoud ES SolimanMolecular Modelling and Drug Design Lab, School of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South AfricaAbstract: Based on experimental data, the anticancer activity of nelfinavir (NFV, a US Food and Drug Administration (FDA-approved HIV-1 protease inhibitor (PI, was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90, a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 µM. Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively. Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602 played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding

  2. FDA (Food and Drug Administration) compliance program guidance manual and updates (FY 86). Section 4. Medical and radiological devices. Irregular report

    International Nuclear Information System (INIS)

    1986-01-01

    The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices

  3. 75 FR 22819 - Considerations Regarding Food and Drug Administration Review and Regulation of Articles for the...

    Science.gov (United States)

    2010-04-30

    ...] Considerations Regarding Food and Drug Administration Review and Regulation of Articles for the Treatment of Rare... Americans, no approved therapies exist. To optimize the means by which FDA considers articles for people... surveillance of, articles for rare diseases. The scope of such presentations may include non-clinical testing...

  4. 76 FR 76978 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2011-12-09

    ... commercial products, such as electronics, food products, and automobiles. Marketing and advertising studies... changes suggested by external peer reviewers and further discussion among research team members. FDA... Noncomparative Advertising: A Meta-Analysis,'' Journal of Marketing, vol. 61, pp. 1-15, 1997. 5. Priester, J.R...

  5. 76 FR 51988 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2011-08-19

    ...) FDA notes that dietary supplement manufacturers making a nutritional deficiency, structure/function... supplement making a nutritional deficiency, structure/function, or general well-being claim have... supplement manufacturers may only need to collect peer-reviewed scientific journal articles to substantiate...

  6. 76 FR 70151 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

    Science.gov (United States)

    2011-11-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0790] Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and Drug Administration Staff; Food and Drug Administration Decisions for Investigational Device Exemption Clinical...

  7. 75 FR 17415 - Determination of Regulatory Review Period for Purposes of Patent Extension; FANAPT

    Science.gov (United States)

    2010-04-06

    ... grants permission to market the drug product. Although only a portion of a regulatory review period may...). FDA recently approved for marketing the human drug product FANAPT (iloperidone). FANAPT is indicated... that the approval of FANAPT represented the first permitted commercial marketing or use of the product...

  8. 75 FR 18213 - Determination of Regulatory Review Period for Purposes of Patent Extension; MOZOBIL

    Science.gov (United States)

    2010-04-09

    ... grants permission to market the drug product. Although only a portion of a regulatory review period may...). FDA recently approved for marketing the human drug product MOZOBIL (plerixafor). MOZOBIL is indicated... of MOZOBIL represented the first permitted commercial marketing or use of the product. Thereafter...

  9. 75 FR 19406 - Determination of Regulatory Review Period for Purposes of Patent Extension; AFINITOR

    Science.gov (United States)

    2010-04-14

    ... grants permission to market the drug product. Although only a portion of a regulatory review period may...). FDA recently approved for marketing the human drug product AFINITOR (everolimus). AFINITOR is... first permitted commercial marketing or use of the product. Thereafter, the Patent and Trademark Office...

  10. 75 FR 17414 - Determination of Regulatory Review Period for Purposes of Patent Extension; TOVIAZ

    Science.gov (United States)

    2010-04-06

    ... grants permission to market the drug product. Although only a portion of a regulatory review period may...). FDA recently approved for marketing the human drug product TOVIAZ (fesoterodine fumarate). TOVIAZ is... first permitted commercial marketing or use of the product. Thereafter, the Patent and Trademark Office...

  11. 76 FR 45271 - Review and Qualification of Clinical Outcome Assessments; Public Workshop

    Science.gov (United States)

    2011-07-28

    ... announcing a public workshop to discuss measurement principles for clinical outcome assessments (COAs) for... appropriate drug development program. Because the qualification process is separate from the drug marketing... other DDTs. This workshop will focus on FDA review principles specific to all type of COAs, i.e., PRO...

  12. 76 FR 77543 - Quantitative Summary of the Benefits and Risks of Prescription Drugs: A Literature Review

    Science.gov (United States)

    2011-12-13

    ... requirement of the Patient Protection and Affordable Care Act (Affordable Care Act). FDA is publishing the... Care Act. DATES: Submit either electronic or written comments on the literature review report by... following methods: Electronic Submissions Submit electronic comments in the following way: Federal e...

  13. 76 FR 45261 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2011-07-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0157... Request; Guidance for Industry: Fast Track Drug Development Programs: Designation, Development, and Application Review AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

  14. 78 FR 65338 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2013-10-31

    ... studies, or in vitro testing. Reports from animal testing are not included. \\3\\ Includes reports of... of IND safety reports, expedite FDA's review of critical safety information, better protect human... risks from clinical trials within 15 calendar days for findings from in vitro testing that suggest a...

  15. 77 FR 70955 - FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products; Report to...

    Science.gov (United States)

    2012-11-28

    ...; Report to Congress on Innovative Products and Treatments for Tobacco Dependence; Public Hearing; Request... innovative products and treatments for tobacco dependence. DATES: The public hearing will be held on December... public hearing will be available for review at the Division of Dockets Management and on the Internet at...

  16. "Bringing a Butter Knife to a Gun Fight"? Salience, Disclosure, and FDA's Differing Approaches to the Tobacco Use and Obesity Epidemics.

    Science.gov (United States)

    Weimholt, Josef

    2015-01-01

    One might expect--given the vastly different look, feel, and function of the ubiquitous (and innocuous) Nutrition Facts panel and the "inflammatory" graphic warning labels for cigarettes--that the statutes establishing such disclosure requirements would exhibit similar disparities. In fact, the relevant provisions of the Nutrition Labeling and Education Act of 1990 and the Family Smoking Prevention and Tobacco Control Act of 2009 are. quite analogous. Like other mandated disclosures, the nutrition label and the cigarette. graphic warnings seek to simultaneously inform and influence consumer decisions. Both statutes grant FDA considerable discretion in.the implementation of the labeling requirements, generally allowing the agency to alter the format and content of the labels as necessary to promote the statutory goals. Thus, the differences in the nutrition and cigarette warning labels are not the product of the statutory schemes alone; rather, they reflect important differences in FDA's interpretation and prioritization of the dual regulatory goals, and in the agency's implicit or explicit assumptions about human behavior.

  17. Investigation of the binding free energies of FDA approved drugs against subtype B and C-SA HIV PR: ONIOM approach.

    Science.gov (United States)

    Sanusi, Z K; Govender, T; Maguire, G E M; Maseko, S B; Lin, J; Kruger, H G; Honarparvar, B

    2017-09-01

    Human immune virus subtype C is the most widely spread HIV subtype in Sub-Sahara Africa and South Africa. A profound structural insight on finding potential lead compounds is therefore necessary for drug discovery. The focus of this study is to rationalize the nine Food and Drugs Administration (FDA) HIV antiviral drugs complexed to subtype B and C-SA PR using ONIOM approach. To achieve this, an integrated two-layered ONIOM model was used to optimize the geometrics of the FDA approved HIV-1 PR inhibitors for subtype B. In our hybrid ONIOM model, the HIV-1 PR inhibitors as well as the ASP 25/25' catalytic active residues were treated at high level quantum mechanics (QM) theory using B3LYP/6-31G(d), and the remaining HIV PR residues were considered using the AMBER force field. The experimental binding energies of the PR inhibitors were compared to the ONIOM calculated results. The theoretical binding free energies (?G bind ) for subtype B follow a similar trend to the experimental results, with one exemption. The computational model was less suitable for C-SA PR. Analysis of the results provided valuable information about the shortcomings of this approach. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide much improved binding energies for complex enzyme drug interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bruno S. Pascoalino

    2016-10-01

    Full Text Available Background The recent epidemics of Zika virus (ZIKV implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4% were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.

  19. Off-label or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs.

    Science.gov (United States)

    O'Reilly, James; Dalal, Amy

    2003-01-01

    Professor O'Reilly's study of recent drug review legislation applies a historical and holistic view of promotion practices for unapproved uses of prescription drugs. He faults Congress for moving public health protections away from a strictly protective mode and toward assistance to drug marketers. He argues that the adverse health consequences of "off-label" promotion of drugs are not well understood, and that the 1997 amendments deserved the public health interest while expanding pharmaceutical company profits.

  20. Why European and United States drug regulators are not speaking with one voice on anti-influenza drugs: regulatory review methodologies and the importance of 'deep' product reviews.

    Science.gov (United States)

    Mulinari, Shai; Davis, Courtney

    2017-11-09

    Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza. In Europe, Relenza was evaluated via the so-called national procedure with Sweden as the reference country. We show that FDA reviewers, unlike their European (i.e. Swedish) counterpart, (1) rejected the manufacturer's insistence on pooling efficacy data, (2) remained wary of subgroup analyses, and (3) insisted on stringent statistical analyses. These differences meant that the FDA was less likely to depart from prevailing regulatory and scientific standards in interpreting trial results. We argue that the differences are explained largely by divergent institutionalised review methodologies, i.e. the European regulator's reliance on manufacturer-compiled summaries compared to the FDA's examination of original data and documentation from trials. The FDA's more probing and meticulous evaluative methodology allowed its reviewers to develop 'deep' knowledge concerning the clinical and statistical facets of trials, and more informed opinions regarding suitable methods for analysing trial results. These findings challenge the current emphasis on evaluating regulatory performance mainly in terms of speed of review. We propose that persistent uncertainty and knowledge deficits regarding NIs could have been ameliorated had regulators engaged in the public debates over the drugs' efficacy and

  1. Ceftaroline fosamil: a brief clinical review.

    Science.gov (United States)

    Shirley, Debbie-Ann T; Heil, Emily L; Johnson, J Kristie

    2013-12-01

    Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.

  2. An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant.

    Science.gov (United States)

    Sanusi, Zainab K; Govender, Thavendran; Maguire, Glenn E M; Maseko, Sibusiso B; Lin, Johnson; Kruger, Hendrik G; Honarparvar, Bahareh

    2018-03-01

    The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to

  3. An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant

    Science.gov (United States)

    Sanusi, Zainab K.; Govender, Thavendran; Maguire, Glenn E. M.; Maseko, Sibusiso B.; Lin, Johnson; Kruger, Hendrik G.; Honarparvar, Bahareh

    2018-03-01

    The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide

  4. Synthesis by spark plasma sintering of a novel protonic/electronic conductor composite: BaCe0.2Zr0.7Y0.1O3−δ /Sr0.95Ti0.9Nb0.1O3−δ (BCZY27/STN95)

    DEFF Research Database (Denmark)

    Fish, Jason; Ricote, Sandrine; Lenrick, Filip

    2013-01-01

    A novel two-phase ceramic composite (cercer) material consisting of a solid solution of barium cerate and -zirconate doped with yttrium (BaCe0.2Zr0.7Y0.1O3−δ : BCZY27), together with niobium-doped strontium titanate (Sr0.95Ti0.9Nb0.1O3−δ : STN95), has been synthesized by solid-state reaction...... and sintered conventionally (CS) at 1350–1500 °C, as well as by spark plasma sintering (SPS) at 1300–1350 °C. CS samples were porous and exhibited high degrees of inter-phase reaction. Nickel oxide sintering aids did not improve CS sample density. In contrast, samples made by SPS were significantly denser (>95...

  5. Considering the Future of Pharmaceutical Promotions in Social Media; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Francesca Renee Dillman Carpentier

    2016-04-01

    Full Text Available This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim’s article of the major themes in recent Food and Drug Administration (FDA warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim’s rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA’s attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media.

  6. Comparisons of human amniotic mesenchymal stem cell viability in FDA-approved collagen-based scaffolds: Implications for engineered diaphragmatic replacement.

    Science.gov (United States)

    Shieh, Hester F; Graham, Christopher D; Brazzo, Joseph A; Zurakowski, David; Fauza, Dario O

    2017-06-01

    We sought to examine amniotic fluid mesenchymal stem cell (afMSC) viability within two FDA-approved collagen-based scaffolds, as a prerequisite to clinical translation of afMSC-based engineered diaphragmatic repair. Human afMSCs were seeded in a human-derived collagen hydrogel and in a bovine-derived collagen sheet at 3 matching densities. Cell viability was analyzed at 1, 3, and 5days using an ATP-based 3D bioluminescence assay. Statistical comparisons were by ANOVA (Pcollagen hydrogel when compared with a collagen sheet. Cell viability can be further optimized by seeding density and time in 3D culture. These data further support the regulatory viability of clinical trials of engineered diaphragmatic repair. N/A (animal and laboratory study). Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

    Science.gov (United States)

    DuMouchel, William; Fram, David; Yang, Xionghu; Mahmoud, Ramy A; Grogg, Amy L; Engelhart, Luella; Ramaswamy, Krishnan

    2008-01-01

    This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. There are consistent and substantial differences between atypical antipsychotic drugs in the

  8. Perkins Nuclear Station, Units 1, 2, and 3: Final environmental statement (Docket Nos. STN 50-488, STN 50-489, and STN 50-490

    International Nuclear Information System (INIS)

    1975-10-01

    The proposed action is the issuance of a construction permit to the Duke Power Company for the construction of the Perkins Nuclear Station (PNS) Units 1, 2, and 3 located in Davie County, North Carolina. A total of 2402 acres will be used for the PNS site; another 1401 acres will be used for the Carter Creek Impoundment. Construction-related activities on the primary site will disturb about 617 acres. Approximately 631 acres of land will be required for transmission line right-of-way, and a railroad spur will affect 77 acres. This constitutes a minor local impact. The heat dissipation system will require a maximum water makeup of 55,816 gpm, of which 50,514 gpm will be consumed due to drift and evaporative losses. This amount represents 4% of the mean monthly flow of the Yadkin River. The cooling tower blowdown and chemical effluents from the station will increase the dissolved solids concentration in the Yadkin River by a maximum of 18 ppm. The thermal alterations and increases in total dissolved solids concentration will not significantly affect the aquatic productivity of the Yadkin River. 26 figs., 51 tabs

  9. Palo Verde Nuclear Generating Station, Units 1, 2 and 3 (Docket Nos. STN 50-528, STN 50-529 and STN 50-530): Final environmental statement

    International Nuclear Information System (INIS)

    1975-09-01

    The proposed action is the issuance of construction permits to the Arizona public Service Company for the construction of the Palo Verde Nuclear Generating Station, Units 1, 2, and 3. Preparation of the 3800-acre site will involve the clearing of up to 2500 acres of land, 1500 of which will be prominently devoted to station facilities. An additional 1200- to 1300-acre evaporation pond will ultimately be developed during the lifetime of the station. About 2200 site acres, previously devoted to agriculture, will be excluded from this land use. Soil disturbance during construction of the station, transmission lines, and water conveyance pipeline will tend to promote erosion and increase siltation in local ephemeral water courses. Stringent measures will be taken to minimize these effects. The total radiation dose to construction workers is estimated to be 15 man-rem. This dose is a small fraction of the approximately 470 man-rem which will be received by the construction force over the same period from natural background radiation. Station, transmission line, and water pipeline construction will kill, remove, displace, or otherwise disturb involved flora and fauna, and will eliminate varying amounts of wildlife breeding, nesting, and forage habitat. These will not be important permanent impacts to the population stability and structure of the involved local ecosystems of the Sonoran desert; however, measures will be taken to minimize such effects as do result form the proposed action

  10. 77 FR 75173 - Comprehensive Assessment of the Process for the Review of Device Submissions; Request for Comments

    Science.gov (United States)

    2012-12-19

    ...) over 5 years. With this additional funding, FDA will be able to hire more than 200 full-time-equivalent... Administration Safety and Innovation Act (Pub. L. 112-144) (FDASIA).\\2\\ Title II of FDASIA is MDUFA III, which... (i.e., those likely to have a significant impact on review times) will be published within 6 months...

  11. 78 FR 101 - Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Reviews for...

    Science.gov (United States)

    2013-01-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0524] Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Reviews for Premarket Approval Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

  12. 77 FR 45357 - Draft Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Review...

    Science.gov (United States)

    2012-07-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0524] Draft Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Review for Premarket Approval Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

  13. 75 FR 34749 - Determination of Regulatory Review Period for Purposes of Patent Extension; BYSTOLIC; U.S. Patent...

    Science.gov (United States)

    2010-06-18

    ... and FDA-2008-E-0267] Determination of Regulatory Review Period for Purposes of Patent Extension; BYSTOLIC; U.S. Patent Nos. 5,759,580 and 6,545,040 AGENCY: Food and Drug Administration, HHS. ACTION... determination because of the submission of applications to the Director of Patents and Trademarks, Department of...

  14. Review of the Clinical Effect of Orlistat

    Science.gov (United States)

    Qi, Xiguang

    2018-01-01

    Obesity has been a main risk for the development of diabetes mellitus, cardiovascular diseases and many other chronic problems worldwide. Lifestyle modification is the best way to lose weight but very hard to implement, thus pharmacotherapy is regarded as a good add-on to dietary and lifestyle therapies. This review provides an overview of the olistat, a drug for obesity approved by FDA, about its mechanism of action, efficacy for obesity and some other diseases including cardiovascular disease, type 2 diabetes and some cancers, as well as its safety and adverse effects.

  15. [U.S. Food and Drug Administration (FDA) strengthens warning that non-aspirin non steroidal anti-inflammatory drugs (NSAIDs) can cause myocardial infarctions or strokes: the dentist's perspective].

    Science.gov (United States)

    Rosen, E; Tsesis, I; Vered, M

    2015-10-01

    This short communication is aimed to update dental practitioners regarding the recently published warning of the U.S. Food and Drug Administration (FDA) regarding the risk for severe cardiovascular complications such as myocardial infarction or stroke following the use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs).

  16. Comparison of Outcomes before and after Ohio's Law Mandating Use of the FDA-Approved Protocol for Medication Abortion: A Retrospective Cohort Study

    Science.gov (United States)

    Combellick, Sarah L.; Kohn, Julia E.; Roberts, Sarah C. M.

    2016-01-01

    Background In February 2011, an Ohio law took effect mandating use of the United States Food and Drug Administration (FDA)-approved protocol for mifepristone, which is used with misoprostol for medication abortion. Other state legislatures have passed or enacted similar laws requiring use of the FDA-approved protocol for medication abortion. The objective of this study is to examine the association of this legal change with medication abortion outcomes and utilization. Methods and Findings We used a retrospective cohort design, comparing outcomes of medication abortion patients in the prelaw period to those in the postlaw period. Sociodemographic and clinical chart data were abstracted from all medication abortion patients from 1 y prior to the law’s implementation (January 2010–January 2011) to 3 y post implementation (February 2011–October 2014) at four abortion-providing health care facilities in Ohio. Outcome data were analyzed for all women undergoing abortion at ≤49 d gestation during the study period. The main outcomes were as follows: need for additional intervention following medication abortion (such as aspiration, repeat misoprostol, and blood transfusion), frequency of continuing pregnancy, reports of side effects, and the proportion of abortions that were medication abortions (versus other abortion procedures). Among the 2,783 medication abortions ≤49 d gestation, 4.9% (95% CI: 3.7%–6.2%) in the prelaw and 14.3% (95% CI: 12.6%–16.0%) in the postlaw period required one or more additional interventions. Women obtaining a medication abortion in the postlaw period had three times the odds of requiring an additional intervention as women in the prelaw period (adjusted odds ratio [AOR] = 3.11, 95% CI: 2.27–4.27). In a mixed effects multivariable model that uses facility-months as the unit of analysis to account for lack of independence by site, we found that the law change was associated with a 9.4% (95% CI: 4.0%–18.4%) absolute increase in

  17. Knowledge management for efficient quantitative analyses during regulatory reviews.

    Science.gov (United States)

    Krudys, Kevin; Li, Fang; Florian, Jeffry; Tornoe, Christoffer; Chen, Ying; Bhattaram, Atul; Jadhav, Pravin; Neal, Lauren; Wang, Yaning; Gobburu, Joga; Lee, Peter I D

    2011-11-01

    Knowledge management comprises the strategies and methods employed to generate and leverage knowledge within an organization. This report outlines the activities within the Division of Pharmacometrics at the US FDA to effectively manage knowledge with the ultimate goal of improving drug development and advancing public health. The infrastructure required for pharmacometric knowledge management includes provisions for data standards, queryable databases, libraries of modeling tools, archiving of analysis results and reporting templates for effective communication. Two examples of knowledge management systems developed within the Division of Pharmacometrics are used to illustrate these principles. The benefits of sound knowledge management include increased productivity, allowing reviewers to focus on research questions spanning new drug applications, such as improved trial design and biomarker development. The future of knowledge management depends on the collaboration between the FDA and industry to implement data and model standards to enhance sharing and dissemination of knowledge.

  18. Application of the Positron Annihilation Technique to the study of vapors absorption process in polyethylene (LDPE) and in imide polymer (6FDA-TMPD PI)

    International Nuclear Information System (INIS)

    Sanchez Mendieta, V.

    1992-01-01

    It is well recognized that positron annihilation lifetime (PAL) spectra in polymers have a long-lived component that can be ascribed to ortho-positronium (o-Ps). The lifetime, τ 3 , is considered to be a measure of the size of the micro-vacancies in which o-Ps is trapped and is annihilated through pick-off annihilation with the rate which depends on the size of the vacancy. Positron lifetime measurements were performed for two different kinds of polymers (low density polyethylene and a polyimide (6FDA-TMPD) during sorption of various vapors (hexane, cyclohexane, benzene, acrylic acid, methyl acrylate, water and oxygen). The vapor sorption affected the long-lived component (ortho-positronium component) in a systematic way regardless of the kind of the vapor molecules, i.e. for the polyethylene both the lifetime and the intensity of the long-lived component were enhanced, while for the polyimide they were decreased significantly. These different effects are interpreted in terms of different states of sorbed molecules in rubbery (the polyethylene) and in glassy (the polyimide) polymers. (Author)

  19. Accurate identification of ALK positive lung carcinoma patients: novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry.

    Directory of Open Access Journals (Sweden)

    Esther Conde

    Full Text Available BACKGROUND: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit and an automated ALK FISH scanning system (FDA-cleared in a series of non-small cell lung cancer tumor samples. METHODS: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit, which was automatically captured and scored by using Bioview's automated scanning system. RESULTS: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. CONCLUSIONS: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.

  20. Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.

    Directory of Open Access Journals (Sweden)

    Louise Egeblad

    Full Text Available To identify interactions a nucleoside analog library (NAL consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of "off target effects." However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA and uridine phosphorylase 1 (UPP1. An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔT(agg around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design.

  1. The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

    Science.gov (United States)

    Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

    2016-01-01

    The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

  2. First derivative emission spectrofluorimetric method for the determination of LCZ696, a newly approved FDA supramolecular complex of valsartan and sacubitril in tablets.

    Science.gov (United States)

    Ragab, Marwa A A; Galal, Shereen M; Korany, Mohamed A; Ahmed, Aya R

    2017-12-01

    LCZ696 (sacubitril/valsartan, Entresto™) is a therapy lately approved by United States Food and Drug Administration (US FDA) as a heart failure therapy. It is claimed to decrease the mortality rate and hospitalization for patients with chronic heart failure. This study is considered as the first report to investigate the fluorimetric behavior of sacubitril in addition to pursuing all the different conditions that may affect its fluorescence. Various conditions were studied, for example studying the effects of organized media, solvents and pH, which may affect the fluorescence behavior of sacubitril. For the simultaneous determination of the newly approved supramolecular complex of valsartan (VAL) and sacubitril (SAC) in their tablets, a sensitive and simple first derivative spectrofluorimetric method was developed. The method involved the measurement of native fluorescence at 416 nm and 314 nm (λ ex 249 nm) for VAL and SAC, respectively. The first (D1) derivative technique was applied to the emission data to resolve a partial overlap that appeared in their emission spectra. The proposed method was successfully applied for the assay of the two drugs in their supramolecular complex LCZ696 with no interference from common pharmaceutical additives. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines were followed in order to validate the proposed method. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry

    Science.gov (United States)

    Conde, Esther; Suárez-Gauthier, Ana; Benito, Amparo; Garrido, Pilar; García-Campelo, Rosario; Biscuola, Michele; Paz-Ares, Luis; Hardisson, David; de Castro, Javier; Camacho, M. Carmen; Rodriguez-Abreu, Delvys; Abdulkader, Ihab; Ramirez, Josep; Reguart, Noemí; Salido, Marta; Pijuán, Lara; Arriola, Edurne; Sanz, Julián; Folgueras, Victoria; Villanueva, Noemí; Gómez-Román, Javier; Hidalgo, Manuel; López-Ríos, Fernando

    2014-01-01

    Background Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Methods Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system. Results All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. Conclusions The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations. PMID:25248157

  4. Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.

    Science.gov (United States)

    Egeblad, Louise; Welin, Martin; Flodin, Susanne; Gräslund, Susanne; Wang, Liya; Balzarini, Jan; Eriksson, Staffan; Nordlund, Pär

    2012-01-01

    To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of "off target effects." However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA) and uridine phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔT(agg) around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design.

  5. Adolescents' perceptions of flavored tobacco products, including E-cigarettes: A qualitative study to inform FDA tobacco education efforts through videogames.

    Science.gov (United States)

    Camenga, D R; Fiellin, L E; Pendergrass, T; Miller, Erica; Pentz, M A; Hieftje, K

    2018-07-01

    Flavored tobacco products have been shown to appeal to youth, however tobacco control strategies have traditionally not focused on these products. To inform the adaptation of an existing videogame to focus on the prevention of flavored tobacco product use, this study explored adolescents' perceptions, beliefs, and social norms surrounding these products, including flavored e-cigarettes. We conducted and analyzed transcripts from seven focus groups with 11-17-year-old adolescents (n = 33) from after-school programs in CT and CA in 2016. Participants discussed flavored tobacco product beliefs and experiences, and how these compared to traditional cigarettes. Thematic analysis of transcripts revealed that participants could name flavors in tobacco products, even though few discussed first-hand experience with the products. Most groups perceived that flavored tobacco product and flavored e-cigarette use facilitated peer approval and acceptance. All groups discussed how youth could easily access flavored tobacco products, including e-cigarettes. Flavoring was a salient aspect of e-cigarette advertisements; however the groups did not recall exposure to other types of flavored tobacco product counter-marketing. These data can help inform the development of tobacco control strategies, novel interventions (such as videogames), and future FDA efforts to prevent adolescent tobacco product use through education and risk communication. Copyright © 2018. Published by Elsevier Ltd.

  6. Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women: A Systematic Review and Meta-analysis

    NARCIS (Netherlands)

    Jaspers, Loes; Feys, Frederik; Bramer, Wichor M.; Franco, Oscar H.; Leusink, Peter; Laan, Ellen T. M.

    2016-01-01

    In August 2015, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. To conduct a systematic review and meta-analysis of randomized clinical trials

  7. The economics of priority review vouchers.

    Science.gov (United States)

    Dimitri, Nicola

    2010-11-01

    Priority review vouchers (PRVs) were introduced in 2007 by the US Congress as an incentive mechanism to spur pharmaceutical firms' R&D efforts for neglected diseases (NDs). A voucher, which a firm can obtain upon approval of a new treatment for NDs, entitles the holder to prioritize the FDA review for any drug. The proposal generated much controversy regarding its ability to effectively stimulate R&D for NDs. Here, after reviewing the main issues of the debate, i use a stylized economic model to discuss the strength of PRVs as an economic incentive to invest in research. My findings suggest that R&D investments might be higher when the developer could prioritize a valuable compound. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. FDA Approvals - Cancer Currents Blog

    Science.gov (United States)

    Blog posts on cancer drugs and devices approved by the Food and Drug Administration—including summaries of the evidence to support the approvals and what they mean for patients—from NCI Cancer Currents.

  9. Contrary Signals from the FDA.

    Science.gov (United States)

    Meyer, Katherine A.; Schultz, William B.

    1984-01-01

    The Reagan administration has taken numerous regulatory actions which are flatly inconsistent with the President's stated political philosophy. Nowhere is this more evident than at the Food and Drug Administration in areas concerning abortion, generic drugs, the denial of information, and medical devices. (RM)

  10. FDA Abbott Infant Formula Recall

    Data.gov (United States)

    U.S. Department of Health & Human Services — On September 22, 2010, Abbott issued a voluntary recall of certain Similac powdered infant formula after identifying a common warehouse beetle (both larvae and...

  11. FDA 101: Regulating Biological Products

    Science.gov (United States)

    ... some medical devices used to produce biologics are regulated by CBER under the FD&C Act's Medical ... لعربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | ف ...

  12. FDA Regulation of Food Labeling

    OpenAIRE

    Yang, Hannah Y.

    1999-01-01

    As one strolls down a grocery aisle, shift through the maze of cosmetic counters, or sits in front of the television, one is transported into various fantasies, identities, and scenarios. The power of advertisements and package designs to influence the consumers has grown tremendously over the years. Food and cosmetic manufacturers, cognizant of this power, have invested an enormous amount of their resources into the both advertising and packaging – so much so that a fissur...

  13. Callaway Plant Units 1 and 2: Final environmental statement (Docket Nos. STN 50-483 and STN 50-486)

    International Nuclear Information System (INIS)

    1975-03-01

    The proposed action is the issuance of a construction permit to the Union Electric company for the construction of the Callaway Plant Units 1 and 2. The Callaway Plant, located 5 m north of the Missouri River in Callaway County, Missouri, will employ a pressurized water reactor to produce up to 3425 megawatts thermal (MWt) from each unit. A steam turbine-generator will use the heat to provide 1120 MWe (net) of electrical power capacity. A stretch power level of 3579 MWt (1160 MWe) is anticipated at a future date and is considered in the assessments contained in this statement. The exhaust steam will be cooled in a closed cycle mode, with water from the Missouri River. Constructing the plant and adjacent facilities will disturb an area of about 600 acres, of which less than 300 acres will be occupied by the operating plant and road and rail access to it. The land presently consists of cropland, pasture and forest. About 1140 acres will be required for the transmission line routes. The land presently consists of forest, pasture and cropland. No unique land usage is involved. Siltation and erosion during construction generally will have minor adverse effects, based upon the extent of protection measures the applicant plans to impose. The effect on Logan Creek is expected to be minor, but further assessment is needed, including possible additional precautions. About 14% of the benthic invertebrate population will be lost in the rectangular area defined by the river width and the length of the area to be dredged for shoreline structures. 28 figs., 53 tabs

  14. Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

    Science.gov (United States)

    DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

    2012-01-01

    Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Cardiovascular, ocular and bone adverse reactions associated with thiazolidinediones: a disproportionality analysis of the US FDA adverse event reporting system database.

    Science.gov (United States)

    Motola, Domenico; Piccinni, Carlo; Biagi, Chiara; Raschi, Emanuel; Marra, Anna; Marchesini, Giulio; Poluzzi, Elisabetta

    2012-04-01

    : The risk of myocardial infarction, macular oedema and bone fractures associated with thiazolidinediones (TZDs) has been extensively investigated. : The aim of the study was to verify if the analysis of a large spontaneous reporting database could generate early signals on these adverse drug reactions (ADRs) associated with TZDs. : A case/non-case study, restricted to antidiabetic drugs, was performed on spontaneous reports of ADRs (2005-2008) in the US FDA Adverse Event Reporting System (AERS). The method was applied to TZDs, both as a drug class and as single agents. The reporting odds ratio (ROR) with 95% CI was calculated as a measure of disproportionality in the whole dataset and in a quarter-by-quarter analysis. : TZD use was registered in 49 589 out of 301 950 drug-reaction pairs (16%), with significant disproportionality for myocardial infarction (ROR 4.71; 95% CI 4.40, 5.05), macular oedema (3.88; 2.79, 5.39) and bone fractures (1.73; 1.53, 1.96). Separate analysis of the two TZDs showed that only rosiglitazone was associated with myocardial infarction (7.86; 7.34, 8.34) and macular oedema (5.55; 3.94, 7.79), whereas pioglitazone was associated with multiple site fractures (2.00; 1.70, 2.35), in particular upper and lower limb and pelvic fractures. The quarter-by-quarter analysis identified disproportionality for myocardial infarction (3.13; 2.38, 4.10) and bone fractures since January-March 2005 (2.70; 1.04, 2.78). : The frequency of reporting of myocardial infarction, macular oedema and fractures was significantly higher for TZDs in comparison with other antidiabetic drugs, with large intraclass differences. Both myocardial infarction and bone fracture signals appeared before major publications on these safety issues.

  16. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie eFeng

    2016-05-01

    Full Text Available Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even if pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

  17. Dietary Supplement Adverse Event Report Data From the FDA Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS), 2004-2013.

    Science.gov (United States)

    Timbo, Babgaleh B; Chirtel, Stuart J; Ihrie, John; Oladipo, Taiye; Velez-Suarez, Loy; Brewer, Vickery; Mozersky, Robert

    2018-05-01

    The Food and Drug Administration (FDA)'s Center for Food Safety and Applied Nutrition (CFSAN) oversees the safety of the nation's foods, dietary supplements, and cosmetic products. To present a descriptive analysis of the 2004-2013 dietary supplement adverse event report (AER) data from CAERS and evaluate the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act as pertaining to dietary supplements adverse events reporting. We queried CAERS for data from the 2004-2013 AERs specifying at least 1 suspected dietary supplement product. We extracted the product name(s), the symptom(s) reported, age, sex, and serious adverse event outcomes. We examined time trends for mandatory and voluntary reporting and performed analysis using SAS v9.4 and R v3.3.0 software. Of the total AERs (n = 15 430) received from January 1, 2004, through December 31, 2013, indicating at least 1 suspected dietary supplement product, 66.9% were mandatory, 32.2% were voluntary, and 0.9% were both mandatory and voluntary. Reported serious outcomes included death, life-threatening conditions, hospitalizations, congenital anomalies/birth defects and events requiring interventions to prevent permanent impairments (5.1%). The dietary supplement adverse event reporting rate in the United States was estimated at ~2% based on CAERS data. This study characterizes CAERS dietary supplement adverse event data for the 2004-2013 period and estimates a reporting rate of 2% for dietary supplement adverse events based on CAERS data. The findings show that the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act had a substantial impact on the reporting of adverse events.

  18. Comparison of Outcomes before and after Ohio's Law Mandating Use of the FDA-Approved Protocol for Medication Abortion: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Ushma D Upadhyay

    2016-08-01

    Full Text Available In February 2011, an Ohio law took effect mandating use of the United States Food and Drug Administration (FDA-approved protocol for mifepristone, which is used with misoprostol for medication abortion. Other state legislatures have passed or enacted similar laws requiring use of the FDA-approved protocol for medication abortion. The objective of this study is to examine the association of this legal change with medication abortion outcomes and utilization.We used a retrospective cohort design, comparing outcomes of medication abortion patients in the prelaw period to those in the postlaw period. Sociodemographic and clinical chart data were abstracted from all medication abortion patients from 1 y prior to the law's implementation (January 2010-January 2011 to 3 y post implementation (February 2011-October 2014 at four abortion-providing health care facilities in Ohio. Outcome data were analyzed for all women undergoing abortion at ≤49 d gestation during the study period. The main outcomes were as follows: need for additional intervention following medication abortion (such as aspiration, repeat misoprostol, and blood transfusion, frequency of continuing pregnancy, reports of side effects, and the proportion of abortions that were medication abortions (versus other abortion procedures. Among the 2,783 medication abortions ≤49 d gestation, 4.9% (95% CI: 3.7%-6.2% in the prelaw and 14.3% (95% CI: 12.6%-16.0% in the postlaw period required one or more additional interventions. Women obtaining a medication abortion in the postlaw period had three times the odds of requiring an additional intervention as women in the prelaw period (adjusted odds ratio [AOR] = 3.11, 95% CI: 2.27-4.27. In a mixed effects multivariable model that uses facility-months as the unit of analysis to account for lack of independence by site, we found that the law change was associated with a 9.4% (95% CI: 4.0%-18.4% absolute increase in the rate of requiring an additional

  19. Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments.

    Science.gov (United States)

    2017-03-23

    On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.

  20. Comparison and analysis of FDA reported visual outcomes of the three latest platforms for LASIK: wavefront guided Visx iDesign, topography guided WaveLight Allegro Contoura, and topography guided Nidek EC-5000 CATz.

    Science.gov (United States)

    Moshirfar, Majid; Shah, Tirth J; Skanchy, David Franklin; Linn, Steven H; Kang, Paul; Durrie, Daniel S

    2017-01-01

    To compare and analyze the differences in visual outcomes between Visx iDesign Advanced WaveScan Studio™ System, Alcon Wavelight Allegro Topolyzer and Nidek EC-5000 using Final Fit™ Custom Ablation Treatment Software from the submitted summary of safety and effectiveness of the US Food and Drug Administration (FDA) data. In this retrospective comparative study, 334 eyes from Visx iDesign, 212 eyes from Alcon Contour, and 135 eyes from Nidek CATz platforms were analyzed for primary and secondary visual outcomes. These outcomes were compared via side-by-side graphical and tabular representation of the FDA data. Statistical significance was calculated when appropriate to assess differences. A P -value LASIK surgery.

  1. Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

    Science.gov (United States)

    Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

    2018-01-16

    This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p disorders were associated with inconsistent unlicensed use. Antipsychotic drug classes, age group, number of prescribed psychotropic drugs, gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license information and package inserts of antipsychotics. The results indicate a need for further clinical pediatric studies and better harmonization between agencies regarding antipsychotic used in pediatrics.

  2. Challenging the FDA's authority to regulate autologous adult stem cells for therapeutic use: Celltex therapeutics' partnership with RNL Bio, substantial medical risks, and the implications of United States v. Regenerative Sciences.

    Science.gov (United States)

    Drabiak-Syed, Katherine

    2013-01-01

    This Article examines the convergence of three corporations that have attempted to capitalize on translating emerging research into clinical procedures by manufacturing and facilitating the process for patients to obtain mesenchymal stem cell (MSC) injections. Although the Food and Drug Administration (FDA) has asserted its authority to regulate somatic cell therapy products like MSCs under the Public Health Service Act and the Food, Drug, and Cosmetic Act, some manufacturers have attempted to circumvent FDA regulation through various mechanisms and argue that their products do not fall within the definition of a biological product or drug. However, scientific knowledge of using MSCs for clinical therapy remains in its infancy, and MSCs pose a number of serious risks to patients. This Article focuses on the development of Celltex, a company based in Sugar Land, Texas that manufactures and facilitates the injection of autologous MSCs; RNL Bio, a company that licenses its operations technology to Celltex; and Regenerative Sciences, a company based in Broomfield, Colorado that was recently involved in litigation with the FDA. Corporate circumvention of intended regulatory oversight exposes patients to potentially inefficacious products that could contribute to serious medical injuries such as viruses, myocardial infarction, cancer, or death.

  3. Adverse event reporting patterns of newly approved drugs in the USA in 2006: an analysis of FDA Adverse Event Reporting System data.

    Science.gov (United States)

    Chhabra, Pankdeep; Chen, Xing; Weiss, Sheila R

    2013-11-01

    The Weber effect states that adverse event (AE) reporting tends to increase in the first 2 years after a new drug is placed onto the market, peaks at the end of the second year, and then declines. However, since the Weber effect was originally described, there has been improvement in the communication of safety information and new policies regarding the reporting of AEs by healthcare professionals and consumers, prompting reassessment of the existence of the Weber effect in the current AE reporting scenario. To determine the AE reporting patterns for new molecular entity (NME) drugs and biologics approved in 2006 and to examine these patterns for the existence of the Weber effect. Publicly available FDA Adverse Event Reporting System data were used to assess the AE reporting patterns for a 5-year period from the drug’s approval date. The total number of annual reports from all sources, based on the report date, was plotted against time (in years). In the period from 2006 to 2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006. The highest number of AE reports were submitted for varenicline tartrate (N = 47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was reported to have the highest proportion of death reports (36 %) and varenicline tartrate the lowest proportion (1.7 %). The classic Weber pattern was not observed for any of the 19 NMEs approved in 2006. While there was no one predominant pattern of AE report volume, we grouped the drugs into four general categories; the majority of drugs had either a continued increase in reports (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in year 2 or 3, declining and then beginning to climb again (Category B 42.1 %). There have been numerous changes in AE reporting, particularly a huge increase in overall annual report volume, since the Weber effect was first reported. Our results suggest that a Weber-type reporting pattern should not be assumed

  4. Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis: A PRISMA-compliant network meta-analysis.

    Science.gov (United States)

    Li, Mei-Juan; Li, Qing; Sun, Min; Liu, Li-Qin

    2017-09-01

    This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg. A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study. For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)]. The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.

  5. WE-G-BRE-06: New Potential for Enhancing External Beam Radiotherapy for Lung Cancer Using FDA-Approved Concentrations of Cisplatin Or Carboplatin Nanoparticles Administered Via Inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Y; Altundal, Y; Sajo, E [University Massachusetts Lowell, Lowell, MA (United States); Detappe, A [Brigham ' Woman' s Hospital, Boston, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); University of Lyon, Lyon (France); Makrigiorgos, G; Berbeco, R [Brigham ' Woman' s Hospital, Boston, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Ngwa, W [University Massachusetts Lowell, Lowell, MA (United States); Brigham ' Woman' s Hospital, Boston, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2014-06-15

    Purpose: This study investigates, for the first time, the dose enhancement to lung tumors due to cisplatin nanoparticles (CNPs) and carboplatin nanoparticles (CBNPs) administered via inhalation route (IR) during external beam radiotherapy. Methods: Using Monte Carlo generated 6 MV energy fluence spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumor due to radiation-induced photoelectrons from CNPs administered via IR in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung tumor via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of CNPs can reach the lung tumors by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the dose with and without CNPs was calculated for field size of 10 cm × 10 cm (sweeping gap), for a range of tumor depths and tumor sizes. Similar calculations were done for CBNPs. Results: For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of 1.19–1.30 were obtained for CNPs at 3–10 cm depth, respectively, in comparison to 1.06–1.09 for IV. For CBNPs, DEF values of 1.26–1.41 were obtained in comparison to 1.07–1.12 for IV. For IR with 14.6 times higher concentrations, higher DEF values were obtained e.g. 1.81–2.27 for CNPs. DEF increased with increasing field size or decreasing tumor size. Conclusions: Our preliminary results indicate that major dose enhancement to lung tumors can be achieved using CNPs/CBNPs administered via IR, in contrast to IV administration during external beam radiotherapy. These findings highlight a potential new approach for radiation boosting to lung tumors using CNPs/CBNPs administered via IR. This would, especially, be applicable during concomitant chemoradiotherapy, potentially allowing for dose enhancement while

  6. Activity trackers: a critical review.

    Science.gov (United States)

    Lee, Jeon; Finkelstein, Joseph

    2014-01-01

    The wearable consumer health devices can be mainly divided into activity trackers, sleep trackers, and stress management devices. These devices are widely advertised to provide positive effects on the user's daily behaviours and overall heath. However, objective evidence supporting these claims appears to be missing. The goal of this study was to review available evidence pertaining to performance of activity trackers. A comprehensive review of available information has been conducted for seven representative devices and the validity of marketing claims was assessed. The device assessment was based on availability of verified output metrics, theoretical frameworks, systematic evaluation, and FDA clearance. The review identified critical absence of supporting evidence of advertised functions and benefits for the majority of the devices. Six out of seven devices did not provide any information on sensor accuracy and output validity at all. Possible underestimation or overestimation of specific health indicators reported to consumers was not clearly disclosed to the public. Furthermore, significant limitations of these devices which can be categorized into user restrictions, user responsibilities and company disclaimers could not be easily found or comprehended by unsophisticated users and may represent a serious health hazard.

  7. A review of class I and class II pet food recalls involving chemical contaminants from 1996 to 2008.

    Science.gov (United States)

    Rumbeiha, Wilson; Morrison, Jamie

    2011-03-01

    Commercial pet food in USA is generally safe, but adulteration does occur. Adulterated food has to be recalled to protect pets and public health. All stakeholders, including food firms, distributors, and government agencies such as the Food and Drug Administration (FDA) participate in food recall. The objective of this review is to describe the pet food recall procedure from start to finish, and to review class I and II pet food recalls from 1996 to 2008, with a specific focus on those due to chemical contaminants/adulterants. Information was requested from the FDA by Freedom of Information Act. Only those recalls backed by the FDA scientific review were considered. The legal framework for food recalls in the Code of Federal Regulations, Title 21, Chapter 1, Part 7 and in the Food and Drug Administration Amendments Act of 2007, Title X was reviewed. From 1996 to 2008, there were a total of 22 class I and II pet food recalls. Of these, only six (27%) were due to chemical adulterants. The adulterants were aflatoxins, cholecalciferol, methionine, and melamine, and cyanuric acid. The causes of adulteration included inadequate testing of raw materials for toxins, use of wrong or faulty mixing equipment, and misformulation of raw materials. Overall, pet food manufactured in the USA is safe. Even with shortcomings in the recall process, the incidence of illness associated with pet food adulteration is low. Added changes can only make the system better in the future to safeguard pet and public safety. © American College of Medical Toxicology 2010

  8. 77 FR 46441 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2012-08-03

    ... a new chapter granting FDA important authority to regulate the manufacture, marketing, and... importance of extending this collection. FDA estimates the burden of this collection of information as...

  9. Review of selected contributions of the conference 'Integrated quality management systems in completion of units 3 and 4 Mochovce'

    International Nuclear Information System (INIS)

    2009-04-01

    There were 14 contributions presented of the conference focused on the integrated quality management systems in completion EMO34. Contributions were focused both on theoretical problems from the project management area and on the applications in practice in management systems implementation in accordance with the standards: STN EN ISO 9001:2000, STN EN ISO 14 001:2005, and OHSAS 18 001:1999 at the completion of the Nuclear Power Plant Mochovce of units 3 and 4

  10. A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Ali Ataya

    2016-12-01

    Full Text Available Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways.

  11. Understanding how perceptions of tobacco constituents and the FDA relate to effective and credible tobacco risk messaging: A national phone survey of U.S. adults, 2014-2015.

    Science.gov (United States)

    Boynton, Marcella H; Agans, Robert P; Bowling, J Michael; Brewer, Noel T; Sutfin, Erin L; Goldstein, Adam O; Noar, Seth M; Ribisl, Kurt M

    2016-06-23

    The passage of the 2009 Family Smoking Prevention and Tobacco Control Act has necessitated the execution of timely, innovative, and policy-relevant tobacco control research to inform Food and Drug Administration (FDA) regulatory and messaging efforts. With recent dramatic changes to tobacco product availability and patterns of use, nationally representative data on tobacco-related perceptions and behaviors are vital, especially for vulnerable populations. The UNC Center for Regulatory Research on Tobacco Communication conducted a telephone survey with a national sample of adults ages 18 and older living in the United States (U.S.). The survey assessed regulatory relevant factors such as tobacco product use, tobacco constituent perceptions, and tobacco regulatory agency credibility. The study oversampled high smoking/low income areas as well as cell phone numbers to ensure adequate representation among smokers and young adults, respectively. Coverage extended to approximately 98 % of U.S. households. The final dataset (N = 5,014) generated weighted estimates that were largely comparable to other national demographic and tobacco use estimates. Results revealed that over one quarter of U.S. adults, and over one third of smokers, reported having looked for information about tobacco constituents in cigarette smoke; however, the vast majority was unaware of what constituents might actually be present. Although only a minority of people reported trust in the federal government, two thirds felt that the FDA can effectively regulate tobacco products. As the FDA continues their regulatory and messaging activities, they should expand both the breadth and availability of constituent-related information, targeting these efforts to reach all segments of the U.S. population, especially those disproportionately vulnerable to tobacco product use and its associated negative health outcomes.

  12. Understanding how perceptions of tobacco constituents and the FDA relate to effective and credible tobacco risk messaging: A national phone survey of U.S. adults, 2014–2015

    Directory of Open Access Journals (Sweden)

    Marcella H. Boynton

    2016-06-01

    Full Text Available Abstract Background The passage of the 2009 Family Smoking Prevention and Tobacco Control Act has necessitated the execution of timely, innovative, and policy-relevant tobacco control research to inform Food and Drug Administration (FDA regulatory and messaging efforts. With recent dramatic changes to tobacco product availability and patterns of use, nationally representative data on tobacco-related perceptions and behaviors are vital, especially for vulnerable populations. Methods The UNC Center for Regulatory Research on Tobacco Communication conducted a telephone survey with a national sample of adults ages 18 and older living in the United States (U.S.. The survey assessed regulatory relevant factors such as tobacco product use, tobacco constituent perceptions, and tobacco regulatory agency credibility. The study oversampled high smoking/low income areas as well as cell phone numbers to ensure adequate representation among smokers and young adults, respectively. Coverage extended to approximately 98 % of U.S. households. Results The final dataset (N = 5,014 generated weighted estimates that were largely comparable to other national demographic and tobacco use estimates. Results revealed that over one quarter of U.S. adults, and over one third of smokers, reported having looked for information about tobacco constituents in cigarette smoke; however, the vast majority was unaware of what constituents might actually be present. Although only a minority of people reported trust in the federal government, two thirds felt that the FDA can effectively regulate tobacco products. Conclusions As the FDA continues their regulatory and messaging activities, they should expand both the breadth and availability of constituent-related information, targeting these efforts to reach all segments of the U.S. population, especially those disproportionately vulnerable to tobacco product use and its associated negative health outcomes.

  13. Still the Great Debate - "Fair Balance" in Direct-to-Consumer Prescription Drug Advertising Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Rollins, Brent L

    2016-02-10

    The above titled paper examined the Food and Drug Administration's (FDA's) warning letters and notice of violations (NOV) over a 10-year period. Findings from this content analysis reinforced what has been the primary issue for prescription direct-to-consumer advertising (DTCA) since its beginning, the fair balance of risk and benefit information. As opposed to another analysis in 2026 about this still being an issue, is there anything that can be done to prevent this problem from continuing? © 2016 by Kerman University of Medical Sciences.

  14. The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.

    Science.gov (United States)

    Adil, Areej; Godwin, Marshall

    2017-07-01

    Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia. This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators. A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process. A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo (P alopecia and that minoxidil is effective in women with androgenetic alopecia. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Present attitudes of physical education students towards future employment in their profession [Současné názory studentů tělesné výchovy na jejich budoucí zaměstnání v této profesi

    Directory of Open Access Journals (Sweden)

    Magdalena Majer

    2010-06-01

    Full Text Available OBJECTIVE: The aim of the research was to examine empirically the attitudes of physical education students towards their future profession in physical culture and some of their considerations about the choice of their field of study and their opinion about the course of studies. METHODS: The research embraced physical education students studying at the Academy of Physical Education in Cracow. The research took place in two stages (May 2005 and 2008. The first part involved first year students (N = 162, the second the same students then being fourth year students, but only those, who passed all semesters on time (N = 103. The students' attitudes towards their future profession were examined by means of a questionnaire worked out by Grabowski and Skrzypiec. RESULTS: For 45.6% of our respondents the choice of their field of study and prospective profession was determined by positive factors. More than half of the tested students (51.6% chose physical education as their field of study because of their interests and passion. Salary, stability and terms of work are also significant factors. More than half of the respondents declare their willingness to work in their profession after graduation. CONCLUSIONS: From among the values preferred while choosing the physical educator's profession, passion was the main choice of the respondents, regardless of gender. The fact that their studies' positive influence on the respondents' attitudes towards their future profession decrease clearly between the first and the last year of studies, is alarming. It would be advisable to do more detailed research in other schools to verify the educational system and the practical preparation of prospective physical education teachers.[CÍLE: Cílem výzkumu bylo empiricky posoudit názory studentů tělesné výchovy na jejich budoucí zaměstnání v tělesné výchově a některé z důvodů, proč si vybrali tento studijní obor, a jejich názory na průběh studia

  16. Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

    Science.gov (United States)

    Elgebaly, Ahmed; Elfil, Mohamed; Attia, Attia; Magdy, Mayar; Negida, Ahmed

    2018-02-01

    Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

  17. Review the 'peer review'.

    Science.gov (United States)

    Blockeel, Christophe; Drakopoulos, Panagiotis; Polyzos, Nikolaos P; Tournaye, Herman; García-Velasco, Juan Antonio

    2017-12-01

    Peer review has been the main form of appraisal of scientific knowledge for over a century. In essence, this process involves the evaluation of a scientific finding by independent experts prior to its dissemination to the scientific community, in an attempt to ensure that both the research and conclusions meet the necessary standards regarding quality, accuracy, relevance and novelty. However, although 'peer review' is considered the current gold standard, it is far from perfect. A focus on the methodology of an article and reviewers' training are key messages for the scientific community. Guidelines on how to review an article are needed and may help reviewers deal with this difficult process. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Impact of physiologically based pharmacokinetic models on regulatory reviews and product labels: Frequent utilization in the field of oncology.

    Science.gov (United States)

    Yoshida, K; Budha, N; Jin, J Y

    2017-05-01

    Physiologically based pharmacokinetic (PBPK) modeling can be used to predict drug pharmacokinetics in virtual populations using models that integrate understanding of physiological systems. PBPK models have been widely utilized for predicting pharmacokinetics in clinically untested scenarios during drug applications and regulatory reviews in recent years. Here, we provide a comprehensive review of the application of PBPK in new drug application (NDA) review documents from the US Food and Drug Administration (FDA) in the past 4 years. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  19. 75 FR 79378 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2010-12-20

    ... Environmental Protection Agency. FDA received a comment relating to the cruelty and sadism of animal testing. In... Request; Testing Communications on FDA-Regulated Products Used in Animals AGENCY: Food and Drug... Communications on FDA-Regulated Products Used in Animals.'' Also include the FDA docket number found in brackets...

  20. Comparison and analysis of FDA reported visual outcomes of the three latest platforms for LASIK: wavefront guided Visx iDesign, topography guided WaveLight Allegro Contoura, and topography guided Nidek EC-5000 CATz

    Directory of Open Access Journals (Sweden)

    Moshirfar M

    2017-01-01

    Full Text Available Majid Moshirfar,1,2 Tirth J Shah,3 David Franklin Skanchy,4 Steven H Linn,1 Paul Kang,3 Daniel S Durrie5 1HDR Research Center, Hoopes Vision, Salt Lake City, UT, 2Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, 3University of Arizona College of Medicine – Phoenix, Phoenix, AZ, 4McGovern Medical School, The University of Texas Health Science Center at Houston, TX, 5Durrie Vision, Kansas City, KS, USA Purpose: To compare and analyze the differences in visual outcomes between Visx iDesign Advanced WaveScan Studio™ System, Alcon Wavelight Allegro Topolyzer and Nidek EC-5000 using Final Fit™ Custom Ablation Treatment Software from the submitted summary of safety and effectiveness of the US Food and Drug Administration (FDA data.Methods: In this retrospective comparative study, 334 eyes from Visx iDesign, 212 eyes from Alcon Contour, and 135 eyes from Nidek CATz platforms were analyzed for primary and secondary visual outcomes. These outcomes were compared via side-by-side graphical and tabular representation of the FDA data. Statistical significance was calculated when appropriate to assess differences. A P-value <0.05 was considered statistically significant. Results: The mean postoperative uncorrected distance visual acuity (UDVA at 12 months was 20/19.25±8.76, 20/16.59±5.94, and 20/19.17±4.46 for Visx iDesign, Alcon Contoura, and Nidek CATz, respectively. In at least 90% of treated eyes at 3 months and 12 months, all three lasers showed either no change or a gain of corrected distance visual acuity (CDVA. Mesopic contrast sensitivity at 6 months showed a clinically significant increase of 41.3%, 25.1%, and 10.6% for eyes using Visx iDesign, Alcon Contoura, and Nidek CATz, respectively. Photopic contrast sensitivity at 6 months showed a clinically significant increase of 19.2%, 31.9%, and 10.6% for eyes using Visx iDesign, Alcon Contoura, and Nidek CATz