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  1. 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

  2. 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...: Notice of availability; request for comments. SUMMARY: As part of the second phase of the Transparency... Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U.S. Food and...

  3. Point-Counterpoint: The FDA Has a Role in Regulation of Laboratory-Developed Tests.

    Science.gov (United States)

    Caliendo, Angela M; Hanson, Kimberly E

    2016-04-01

    Since the Food and Drug Administration (FDA) released its draft guidance on the regulation of laboratory-developed tests (LDTs) in October 2014, there has been a flurry of responses from commercial and hospital-based laboratory directors, clinicians, professional organizations, and diagnostic companies. The FDA defines an LDT as an "in vitrodiagnostic device that is intended for clinical use and is designed, manufactured, and used within a single laboratory." The draft guidance outlines a risk-based approach, with oversight of high-risk and moderate-risk tests being phased in over 9 years. High-risk tests would be regulated first and require premarket approval. Subsequently, moderate-risk tests would require a 510(k) premarket submission to the FDA and low-risk tests would need only to be registered. Oversight discretion would be exercised for LDTs focused on rare diseases (defined as fewer than 4,000 tests, not cases, per year nationally) and unmet clinical needs (defined as those tests for which there is no alternative FDA-cleared or -approved test). There was an open comment period followed by a public hearing in early January of 2015, and we are currently awaiting the final decision regarding the regulation of LDTs. Given that LDTs have been developed by many laboratories and are essential for the diagnosis and monitoring of an array of infectious diseases, changes in their regulation will have far-reaching implications for clinical microbiology laboratories. In this Point-Counterpoint, Angela Caliendo discusses the potential benefits of the FDA guidance for LDTs whereas Kim Hanson discusses the concerns associated with implementing the guidance and why these regulations may not improve clinical care. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Price, performance, and the FDA approval process: the example of home HIV testing.

    Science.gov (United States)

    Paltiel, A David; Pollack, Harold A

    2010-01-01

    The Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To support its decision, the FDA seeks evidence of the test's performance. It has asked the manufacturer to conduct field studies of the test's sensitivity and specificity when employed by untrained users. In this article, the authors argue that additional information should be sought to evaluate the prevalence of undetected HIV in the end-user The analytic framework produces the elementary but counterintuitive finding that the performance of the home HIV test- measured in terms of its ability to correctly detect the presence and absence of HIV infection among the people who purchase it-depends critically on the manufacturer's retail price. This finding has profound implications for the FDA's approval process.

  5. New Advantage 24 contraceptive gel claims 24-hour effectiveness. But proposed FDA rule could put N-9 products to the test.

    Science.gov (United States)

    1995-04-01

    Advantage 24 is a new contraceptive gel that makes use of bioadhesive technology to offer 24 hours of protection relying on the spermicide nonoxynol-9 (N-9) in lower concentrations. If a proposed US Food and Drug Administration (FDA) rule is enforced N-9 may be examined closely. The manufacturer, Whitehall-Robins Healthcare in New Jersey, stopped production of the Today contraceptive sponge because of the costs of complying with FDA standards. The Advantage 24 gel costs twice as much as the sponge. It is made in Switzerland and distributed by an Illinois company. Any vaginal contraceptive containing N-9 would be approved by the FDA as long as it complied with guidelines laid down in an FDA monograph. However, the registration of the gel could not be confirmed. The product uses a bioadhesive technology concept that natural substances adhere to epithelial and mucosal tissues in the body. Polycarbofil is mixed with water, N-9, and mineral oil to create an emulsion that allows for a time-release mechanism, but at any given time only 2 mg of N-9 is available to kill sperm. The final formula for Advantage 24 is 52.5 mg per dose. Too much N-9 can be toxic, as demonstrated by the Today sponge, which contained 1000 mg of N-9. In Kenya prostitutes using it frequently experienced 3 times as many genital lesions as those using a placebo. A study of Advantage 24 by a Miami laboratory involved 250 women, 22-45 years old, who had had prior tubal ligations. When the gel was applied 15-30 minutes before intercourse the efficacy rate was 98%; it was 91% for those applying it 12 hours before; and it was 86% when the gel was applied 24 hours ahead of time. FDA compliance officers are intrigued about the claim that the gel lasts 24 hours. However, if the claim is held up by research data, women will have an easily available, portable, efficient, aesthetic, and highly effective contraceptive.

  6. 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 ...

  7. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  8. 78 FR 60287 - Agency Information Collection Activities; Proposed Collection; Comment Request; Testing...

    Science.gov (United States)

    2013-10-01

    ... communication strategies, messages, and labels. These communications will aim to improve public understanding of... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1164] Agency Information Collection Activities; Proposed Collection; Comment Request; Testing Communications on...

  9. 75 FR 51271 - Agency Information Collection Activities; Proposed Collection; Comment Request; Testing...

    Science.gov (United States)

    2010-08-19

    ... communication strategies, messages, and labels. These communications will aim to improve public understanding of... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0420] Agency Information Collection Activities; Proposed Collection; Comment Request; Testing Communications on...

  10. 75 FR 39952 - Agency Information Collection Activities; Proposed Collection; Comment Request; Testing...

    Science.gov (United States)

    2010-07-13

    ... communications will aim to improve public understanding of the risks and benefits of using medical devices and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0344] Agency Information Collection Activities; Proposed Collection; Comment Request; Testing Communications on...

  11. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR Staging

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  12. Subarray-based FDA radar to counteract deceptive ECM signals

    Science.gov (United States)

    Abdalla, Ahmed; Wang, Wen-Qin; Yuan, Zhao; Mohamed, Suhad; Bin, Tang

    2016-12-01

    In recent years, the frequency diverse array (FDA) radar concept has attracted extensive attention, as it may benefit from a small frequency increment, compared to the carrier frequency across the array elements and thereby achieve an array factor that is a function of the angle, the time, and the range which is superior to the conventional phase array radar (PAR). However, limited effort on the subject of FDA in electronic countermeasure scenarios, especially in the presence of mainbeam deceptive jamming, has been published. Basic FDA is not desirable for anti-jamming applications, due to the range-angle coupling response of targets. In this paper, a novel method based on subarrayed FDA signal processing is proposed to counteract deceptive ECM signals. We divide the FDA array into multiple subarrays, each of which employs a distinct frequency increment. As a result, in the subarray-based FDA, the desired target can be distinguished at subarray level in joint range-angle-Doppler domain by utilizing the fact that the jammer generates false targets with the same ranges to each subarray without reparations. The performance assessment shows that the proposed solution is effective for deceptive ECM targets suppression. The effectiveness is verified by simulation results.

  13. 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

  14. 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

  15. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus.

    Science.gov (United States)

    Ekins, Sean; Freundlich, Joel S; Coffee, Megan

    2014-01-01

    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.

  16. 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

  17. 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...

  18. 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.

  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. 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

  1. 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...

  2. 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.

  3. 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.

  4. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... see the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

  5. 78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

    Science.gov (United States)

    2013-03-05

    ... FDA's Product Tracing Web page at http://www.fda.gov/Food/FoodSafety/FSMA/ucm270851.htm . This... Submit a Report to Congress for the Improvement of Tracking and Tracing of Food; Request for Comments and... Institute of Food Technologists (IFT) to execute product tracing pilot projects as described in the FDA Food...

  6. 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

  7. 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...

  8. Regulating nanomedicine - can the FDA handle it?

    Science.gov (United States)

    Bawa, Raj

    2011-05-01

    There is enormous excitement and expectation surrounding the multidisciplinary field of nanomedicine - the application of nanotechnology to healthcare - which is already influencing the pharmaceutical industry. This is especially true in the design, formulation and delivery of therapeutics. Currently, nanomedicine is poised at a critical stage. However, regulatory guidance in this area is generally lacking and critically needed to provide clarity and legal certainty to manufacturers, policymakers, healthcare providers as well as public. There are hundreds, if not thousands, of nanoproducts on the market for human use but little is known of their health risks, safety data and toxicity profiles. Less is known of nanoproducts that are released into the environment and that come in contact with humans. These nanoproducts, whether they are a drug, device, biologic or combination of any of these, are creating challenges for the Food and Drug Administration (FDA), as regulators struggle to accumulate data and formulate testing criteria to ensure development of safe and efficacious nanoproducts (products incorporating nanoscale technologies). Evidence continues to mount that many nanoproducts inherently posses novel size-based properties and toxicity profiles. Yet, this scientific fact has been generally ignored by the FDA and the agency continues to adopt a precautionary approach to the issue in hopes of countering future potential negative public opinion. As a result, the FDA has simply maintained the status quo with regard to its regulatory policies pertaining to nanomedicine. Therefore, there are no specific laws or mechanisms in place for oversight of nanomedicine and the FDA continues to treat nanoproducts as substantially equivalent ("bioequivalent") to their bulk counterparts. So, for now nanoproducts submitted for FDA review will continue to be subjected to an uncertain regulatory pathway. Such regulatory uncertainty could negatively impact venture funding, stifle

  9. 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.

  10. 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.

  11. Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

    Science.gov (United States)

    Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

    2016-07-15

    In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. 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

  13. FDA: polyurethane condom carries "extremely misleading" label. Federal agency allows distribution for public health's sake.

    Science.gov (United States)

    1995-02-01

    The labeling of the Avanti polyurethane condom selling in 10 Western states makes misleading claims about protection from pregnancy and sexually transmitted diseases (STDs) according to officials at the US Food and Drug Administration (FDA). Avanti is sold in a foil package printed with the claim that it is effective against pregnancy, HIV, and STDs. However, polyurethane condoms have not undergone clinical efficacy testing for contraception or STDs, according to officials. The manufacturer of the condom refuted this allegation, stating that latex condoms have the same claims on them. In early 1995 the FDA met with the manufacturer and other companies developing plastic condoms, and concluded that these condoms could not make such claims, nor any claims about slippage and breakage rates. Despite warnings in 1993 to the manufacturer of Avanti about labeling restrictions, the company printed pregnancy and STD efficacy claims on the boxes and individual packages. The FDA later worked out a compromise with the firm in which only the boxes had to be reprinted with the generic label. The FDA had to weigh the risk of the public health cost of delaying sale of the condom, which is the first impermeable condom proven safe for people with latex allergies. In 1991 the FDA was defining standards for clinical testing and labeling of polyurethane condoms under congressional mandate, but the manufacturer of Avanti began mass production based on a preliminary approval determining that the condom was equivalent to latex condoms already on the market. 7000 Avanti condoms were subsequently tested in five countries, but these user tests did not compare Avanti to latex condoms and did not test for pregnancy and STD protection. Test results submitted to the FDA by the company indicated that, although Avanti is more than 1/3 less elastic than latex condoms, it did not break more frequently in an in-use study involving 187 couples.

  14. 21 CFR 60.34 - FDA action on petitions.

    Science.gov (United States)

    2010-04-01

    ... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... this section or investigate and determine under § 60.36 whether the applicant acted with due diligence during the regulatory review period. FDA will publish its due diligence determination in the Federal...

  15. 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.

  16. 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.

  17. Right to experimental treatment: FDA new drug approval, constitutional rights, and the public's health.

    Science.gov (United States)

    Leonard, Elizabeth Weeks

    2009-01-01

    On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, held that terminally ill patients who have exhausted all other available options have a constitutional right to experimental treatment that FDA has not yet approved. Although ultimately overturned by the full court, Abigail Alliance generated considerable interest from various constituencies. Meanwhile, FDA proposed similar regulatory amendments, as have lawmakers on both sides of the aisle in Congress. But proponents of expanded access fail to consider public health and consumer safety concerns. In particular, allowing patients to try unproven treatments, outside of controlled clinical trials risks both the study's outcome and the health of patients who might benefit from the deliberate, careful process of new drug approval as it currently operates under FDA's auspices.

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus [v2; ref status: indexed, http://f1000r.es/4wt

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2014-12-01

    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.

  4. 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.

  5. 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....

  6. 76 FR 1180 - FDA Transparency Initiative: Improving Transparency to Regulated Industry

    Science.gov (United States)

    2011-01-07

    ...] FDA Transparency Initiative: Improving Transparency to Regulated Industry AGENCY: Food and Drug... the Transparency Initiative, the Food and Drug Administration (FDA) is announcing the availability of a report entitled ``FDA Transparency Initiative: Improving Transparency to Regulated Industry.'' The...

  7. 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...

  8. Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

    Science.gov (United States)

    Deyo, Richard A

    2004-01-01

    Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

  9. Gottlieb, the FDA and dumbing down medicine

    OpenAIRE

    Robbins RA

    2017-01-01

    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 wh...

  10. 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 …

  11. 42 CFR 405.203 - FDA categorization of investigational devices.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational.../investigational (Category A) or non-experimental/investigational (Category B). (c) CMS uses the categorization of...

  12. 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.

  13. Science, law, and politics in the Food and Drug Administration's genetically engineered foods policy: FDA's 1992 policy statement.

    Science.gov (United States)

    Pelletier, David L

    2005-05-01

    The US Food and Drug Administration's (FDA's) 1992 policy statement was developed in the context of critical gaps in scientific knowledge concerning the compositional effects of genetic transformation and severe limitations in methods for safety testing. FDA acknowledged that pleiotropy and insertional mutagenesis may cause unintended changes, but it was unknown whether this happens to a greater extent in genetic engineering compared with traditional breeding. Moreover, the agency was not able to identify methods by which producers could screen for unintended allergens and toxicants. Despite these uncertainties, FDA granted genetically engineered foods the presumption of GRAS (Generally Recognized As Safe) and recommended that producers use voluntary consultations before marketing them.

  14. 78 FR 41066 - Agency Information Collection Activities; Proposed Collection; Comment Request; Testing...

    Science.gov (United States)

    2013-07-09

    ... provide the better understanding of target audiences that FDA needs to design effective communication strategies, messages, and labels. These communications will aim to improve public understanding of the risks... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0796...

  15. 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...

  16. 75 FR 61492 - Agency Information Collection Activities; Proposed Collection; Comment Request; Testing...

    Science.gov (United States)

    2010-10-05

    ... understanding of target audiences that FDA needs to design effective communication strategies, messages, and labels. These communications will aim to improve public understanding of the risks and benefits of using... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0464...

  17. 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.

  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. A hardenability test proposal

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, N.V.S.N. [Ingersoll-Rand (I) Ltd., Bangalore (India)

    1996-12-31

    A new approach for hardenability evaluation and its application to heat treatable steels will be discussed. This will include an overview and deficiencies of the current methods and discussion on the necessity for a new approach. Hardenability terminology will be expanded to avoid ambiguity and over-simplification as encountered with the current system. A new hardenability definition is proposed. Hardenability specification methods are simplified and rationalized. The new hardenability evaluation system proposed here utilizes a test specimen with varying diameter as an alternative to the cylindrical Jominy hardenability test specimen and is readily applicable to the evaluation of a wide variety of steels with different cross-section sizes.

  20. 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...

  1. 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.

  2. 77 FR 22247 - Veterinary Feed Directive; Draft Text for Proposed Regulation

    Science.gov (United States)

    2012-04-13

    .... FDA-2010-N-0155] Veterinary Feed Directive; Draft Text for Proposed Regulation AGENCY: Food and Drug... the efficiency of FDA's Veterinary Feed Directive (VFD) program. The Agency is making this draft text..., rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Sharon Benz, Center for Veterinary...

  3. 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.

  4. Environmental assessments and findings of no significant impact--FDA. Notice.

    Science.gov (United States)

    1998-05-18

    The Food and Drug Administration (FDA) is announcing that it has reviewed environmental assessments (EA's) and issued findings of no significant impact (FONSI's) relating to the 167 new drug applications (NDA's) and supplemental applications listed in this document. FDA is publishing this notice because Federal regulations require public notice of the availability of environmental documents.

  5. 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...

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

    KAUST Repository

    Xu, Liren; Zhang, Chen; Rungta, Meha; Qiu, Wulin; Liu, Junqiang; Koros, William J.

    2014-01-01

    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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.; Ghanem, Bader; Alghunaimi, Fahd; Litwiller, Eric; Pinnau, Ingo

    2016-01-01

    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.

  13. 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.

  14. 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...

  15. Could FDA approval of pre-exposure prophylaxis make a difference? A qualitative study of PrEP acceptability and FDA perceptions among men who have sex with men.

    Science.gov (United States)

    Underhill, Kristen; Morrow, Kathleen M; Operario, Don; Mayer, Kenneth H

    2014-02-01

    The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while others perceived approval as irrelevant or less significant than other sources of information. Our results suggest that FDA approval sends a signal that directly shapes PrEP acceptability among some MSM, while indirect influences of approval may affect uptake by others. Efforts to educate MSM about PrEP can increase acceptability by incorporating information about FDA approval, and outreach strategies should consider how this information may factor into personal decisions about PrEP use.

  16. 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.

  17. Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.

    Science.gov (United States)

    Li, Chunfeng; Zhu, Xingliang; Ji, Xue; Quanquin, Natalie; Deng, Yong-Qiang; Tian, Min; Aliyari, Roghiyh; Zuo, Xiangyang; Yuan, Ling; Afridi, Shabbir Khan; Li, Xiao-Feng; Jung, Jae U; Nielsen-Saines, Karin; Qin, Frank Xiao-Feng; Qin, Cheng-Feng; Xu, Zhiheng; Cheng, Genhong

    2017-10-01

    Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public. Copyright © 2017. Published by Elsevier B.V.

  18. 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.

  19. 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

  20. 76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

    Science.gov (United States)

    2011-05-24

    ... consider public release of financial disclosure information related to an approved marketing application...] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial... entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by Clinical...

  1. FDA approved drugs as potential Ebola treatments [v2; ref status: indexed, http://f1000r.es/554

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-03-01

    Full Text Available In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available.

  2. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    Science.gov (United States)

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units , which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the

  3. 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.

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

    Science.gov (United States)

    Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S

    2011-01-01

    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 advertisements

  5. 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

  6. Emerging Resistance, New Antimicrobial Agents  …  but No Tests! The Challenge of Antimicrobial Susceptibility Testing in the Current US Regulatory Landscape.

    Science.gov (United States)

    Humphries, R M; Hindler, J A

    2016-07-01

    Accurate and timely performance of antimicrobial susceptibility testing (AST) by the clinical laboratory is paramount to combating antimicrobial resistance. The ability of laboratories in the United States to effectively perform ASTs is challenged by several factors. Some, such as new resistance mechanisms and the associated evolution of testing recommendations and breakpoints, are inevitable. Others are entirely man-made. These include unnecessarily strict US Food and Drug Administration (FDA) limitations on how commercial AST systems can be used for diagnostic testing, the absence of up-to-date performance data on these systems, and the lack of commercially available FDA-cleared tests for newer antimicrobial agents or for older agents with updated breakpoints. This viewpoint will highlight contemporary AST challenges faced by the clinical laboratory, and propose some solutions. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

    Science.gov (United States)

    Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

    2007-01-01

    Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

  8. 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.

  9. Experiences of the REACH testing proposals system to reduce animal testing.

    Science.gov (United States)

    Taylor, Katy; Stengel, Wolfgang; Casalegno, Carlotta; Andrew, David

    2014-01-01

    In order to reduce animal testing, companies registering chemical substances under the EU REACH legislation must propose rather than conduct certain tests on animals. Third parties can submit 'scientifically valid information' relevant to these proposals to the Agency responsible, the European Chemicals Agency (ECHA), who are obliged to take the information into account. The European Coalition to End Animal Experiments (ECEAE) provided comments on nearly half of the 817 proposals for vertebrate tests on 480 substances published for comment for the first REACH deadline (between 1 August 2009 and 31 July 2012). The paper summarises the response by registrants and the Agency to third party comments and highlights issues with the use of read across, in vitro tests, QSAR and weight of evidence approaches. Use of existing data and evidence that testing is legally or scientifically unjustified remain the most successful comments for third parties to submit. There is a worrying conservatism within the Agency regarding the acceptance of alternative approaches and examples of where registrants have also failed to maximise opportunities to avoid testing.

  10. 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...

  11. FDA's Activities Supporting Regulatory Application of "Next Gen" Sequencing Technologies.

    Science.gov (United States)

    Wilson, Carolyn A; Simonyan, Vahan

    2014-01-01

    Applications of next-generation sequencing (NGS) technologies require availability and access to an information technology (IT) infrastructure and bioinformatics tools for large amounts of data storage and analyses. The U.S. Food and Drug Administration (FDA) anticipates that the use of NGS data to support regulatory submissions will continue to increase as the scientific and clinical communities become more familiar with the technologies and identify more ways to apply these advanced methods to support development and evaluation of new biomedical products. FDA laboratories are conducting research on different NGS platforms and developing the IT infrastructure and bioinformatics tools needed to enable regulatory evaluation of the technologies and the data sponsors will submit. A High-performance Integrated Virtual Environment, or HIVE, has been launched, and development and refinement continues as a collaborative effort between the FDA and George Washington University to provide the tools to support these needs. The use of a highly parallelized environment facilitated by use of distributed cloud storage and computation has resulted in a platform that is both rapid and responsive to changing scientific needs. The FDA plans to further develop in-house capacity in this area, while also supporting engagement by the external community, by sponsoring an open, public workshop to discuss NGS technologies and data formats standardization, and to promote the adoption of interoperability protocols in September 2014. Next-generation sequencing (NGS) technologies are enabling breakthroughs in how the biomedical community is developing and evaluating medical products. One example is the potential application of this method to the detection and identification of microbial contaminants in biologic products. In order for the U.S. Food and Drug Administration (FDA) to be able to evaluate the utility of this technology, we need to have the information technology infrastructure and

  12. 78 FR 35279 - Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic Products

    Science.gov (United States)

    2013-06-12

    ... proposed extension of an existing collection of information, and to allow 60 days for public comment in...)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in... Products'' FDA Form 3646 ``Mercury Vapor Lamp Products Radiation Safety Report'' FDA Form 3647 ``Guide for...

  13. 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

  14. 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

  15. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.

  16. FDA publishes checklist of Y2K high-risk devices.

    Science.gov (United States)

    1999-09-01

    Key points. The federal Food and Drug Administration (FDA) has developed a list of types of medical devices that have the potential for the most serious consequences for patients should they fail because of Y2K-related problems. This list of computer-controlled potentially high-risk devices can provide a guide to health care facilities regarding the types of devices that should receive priority in their assessment and remediation of medical devices. The list may change as the FDA receives comments on the types of devices included in the list.

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

    KAUST Repository

    Zhang, Chen; Dai, Ying; Johnson, Justin R.; Karvan, Oguz; Koros, William J.

    2012-01-01

    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.

  18. 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.

  19. 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

  20. Assessing Willingness to Test for HIV among Men who have Sex with Men Using Conjoint Analysis, Evidence for Uptake of the FDA-approved at-Home HIV Test

    Science.gov (United States)

    Lee, Sung-Jae; Brooks, Ronald; Bolan, Robert K.; Flynn, Risa

    2013-01-01

    Men who have sex with men (MSM) in the United States represent a vulnerable population with lower rates of HIV testing. There are various specific attributes of HIV testing that may impact willingness to test (WTT) for HIV. Identifying specific attributes influencing patients’ decisions around WTT for HIV is critical to ensure improved HIV testing uptake. This study examined WTT for HIV by using conjoint analysis, an innovative method for systematically estimating consumer preferences across discrete attributes. WTT for HIV was assessed across eight hypothetical HIV testing scenarios varying across seven dichotomous attributes: location (home vs. clinic), price (free vs. $50), sample collection (finger prick vs. blood), timeliness of results (immediate vs. 1–2 weeks), privacy (anonymous vs. confidential), results given (by phone vs. in-person), and type of counseling (brochure vs. in-person). Seventy-five MSM were recruited from a community based organization providing HIV testing services in Los Angeles to participate in conjoint analysis. WTT for HIV score was based on a 100-point scale. Scores ranged from 32.2 to 80.3 for eight hypothetical HIV testing scenarios. Price of HIV testing (free vs. $50) had the highest impact on WTT (impact score=31.4, SD=29.2, p<.0001), followed by timeliness of results (immediate vs. 1–2 weeks) (impact score=13.9, SD=19.9, p=<.0001) and testing location (home vs. clinic) (impact score=10.3, SD=22.8, p=.0002). Impacts of other HIV testing attributes were not significant. Conjoint analysis method enabled direct assessment of HIV testing preferences and identified specific attributes that significantly impact WTT for HIV among MSM. This method provided empirical evidence to support the potential uptake of the newly FDA-approved over-the-counter HIV home-test kit with immediate results, with cautionary note on the cost of the kit. PMID:23651439

  1. 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 ...

  2. 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.

  3. 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...

  4. Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepancies remain.

    Science.gov (United States)

    Chambers, James D; May, Katherine E; Neumann, Peter J

    2013-06-01

    The Food and Drug Administration (FDA) and Medicare use different standards to determine, first, whether a new drug or medical device can be marketed to the public and, second, if the federal health insurance program will pay for use of the drug or device. This discrepancy creates hurdles and uncertainty for drug and device manufacturers. We analyzed discrepancies between FDA approval and Medicare national coverage determinations for sixty-nine devices and Part B drugs approved during 1999-2011. We found that Medicare covered FDA-approved drugs or devices 80 percent of the time. However, Medicare often added conditions beyond FDA approval, particularly for devices and most often restricting coverage to patients with the most severe disease. In some instances, Medicare was less restrictive than the FDA. Our findings highlight the importance for drug and device makers of anticipating Medicare's needs when conducting clinical studies to support their products. Our findings also provide important insights for the FDA's and Medicare's pilot parallel review program.

  5. 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.

  6. 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

  7. Could FDA approval of pre-exposure prophylaxis make a difference? A qualitative study of PrEP acceptability and FDA perceptions among men who have sex with men

    OpenAIRE

    Underhill, Kristen; Morrow, Kathleen M.; Operario, Don; Mayer, Kenneth H.

    2014-01-01

    The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while o...

  8. Customizable orthopaedic oncology implants: one institution's experience with meeting current IRB and FDA requirements.

    Science.gov (United States)

    Willis, Alexander R; Ippolito, Joseph A; Patterson, Francis R; Benevenia, Joseph; Beebe, Kathleen S

    2016-01-01

    Customizable orthopaedic implants are often needed for patients with primary malignant bone tumors due to unique anatomy or complex mechanical problems. Currently, obtaining customizable orthopaedic implants for orthopaedic oncology patients can be an arduous task involving submitting approval requests to the Institutional Review Board (IRB) and the Food and Drug Administration (FDA). There is great potential for the delay of a patient's surgery and unnecessary paperwork if the submission pathways are misunderstood or a streamlined protocol is not in place. The objective of this study was to review the existing FDA custom implant approval pathways and to determine whether this process was improved with an institutional protocol. An institutional protocol for obtaining IRB and FDA approval for customizable orthopaedic implants was established with the IRB at our institution in 2013. This protocol was approved by the IRB, such that new patients only require submission of a modification to the existing protocol with individualized patient information. During the two-year period of 2013-2014, eight patients were retrospectively identified as having required customizable implants for various orthopaedic oncology surgeries. The dates of request for IRB approval, request for FDA approval, and total time to surgery were recorded, along with the specific pathway utilized for FDA approval. The average patient age was 12 years old (7-21 years old). The average time to IRB approval of a modification to the pre-approved protocol was 14 days (7-21 days). Average time to FDA approval after submission of the IRB approval to the manufacturer was 12.5 days (7-19 days). FDA approval was obtained for all implants as compassionate use requests in accordance with Section 561 of the Federal Food Drug and Cosmetic Act's expanded access provisions. Establishment of an institutional protocol with pre-approval by the IRB can expedite the otherwise time-consuming and complicated

  9. FDA cigarette warning labels lower craving and elicit frontoinsular activation in adolescent smokers

    Science.gov (United States)

    Do, Kathy T.

    2015-01-01

    Cigarette smoking is an economically and epidemiologically expensive public health concern. Most adult smokers become addicted during adolescence, rendering it a crucial period for prevention and intervention. Although litigation claims have delayed implementation, graphic warning labels proposed by the U.S. Food and Drug Administration (FDA) may be a promising way to achieve this goal. We aimed to determine the efficacy of the labels in reducing in-scanner craving and to characterize the neurobiological responses in adolescent and adult smokers and non-smokers. While undergoing functional magnetic resonance imaging, thirty-nine 13- to 18-year-old adolescent and forty-one 25- to 30-year-old adult smokers and non-smokers rated their desire to smoke when presented with emotionally graphic warning labels and comparison non-graphic labels. Compared with adult smokers, adolescent smokers exhibited greater craving reduction in response to the warning labels. Although smokers evinced overall blunted recruitment of insula and dorsolateral prefrontal cortex (DLPFC) relative to non-smokers, an effect that was stronger in adolescent smokers, parametrically increasing activation of these regions was associated with greater craving reduction. Functional connectivity analyses suggest that greater DLPFC regulation of limbic regions predicted cigarette craving. These data underscore a prominent role of frontoinsular circuitry in predicting the efficacy of FDA graphic warning labels in craving reduction in adult and adolescent smokers. PMID:25887154

  10. 76 FR 39105 - Beiersdorf, Inc.; Analysis of Proposed Consent Order To Aid Public Comment

    Science.gov (United States)

    2011-07-05

    ... proposed order. This matter involves the advertising, marketing, and sale of ``NIVEA My Silhouette... regulations issued by the FDA under the Nutrition Labeling and Education Act of 1990. Part V of the proposed...

  11. Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication

    Directory of Open Access Journals (Sweden)

    Bander Balkhi

    2018-02-01

    Conclusions: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

  12. 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

  13. Regulating (for the benefit of) future persons: a different perspective on the FDA's jurisdiction to regulate human reproductive cloning.

    Science.gov (United States)

    Javitt, Gail H; Hudson, Kathy

    2003-01-01

    The Food and Drug Administration (FDA) has taken the position that human reproductive cloning falls within its regulatory jurisdiction. This position has been subject to criticism on both procedural and substantive grounds. Some have contended that the FDA has failed to follow administrative law principles in asserting its jurisdiction, while others claim the FDA is ill suited to the task of addressing the ethical and social implications of human cloning. This Article argues, that, notwithstanding these criticisms, the FDA could plausibly assert jurisdiction over human cloning as a form of human gene therapy, an area in which the FDA is already regarded as having primary regulatory authority. Such an assertion would require that the FDA's jurisdiction extend to products affecting future persons, i.e., those not yet born. This Article demonstrates, for the first time, that such jurisdiction was implicit in the enactment of the 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act and that the FDA has historically relied on such authority in promulgating regulations for drugs and devices.

  14. Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Isidro Palos

    2017-06-01

    Full Text Available Chagas disease (CD is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn as cruzain (Cz inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin showed better trypanocidal effects (LC50 range 15.8–26.1 μg/mL in comparison with benznidazole and nifurtimox (LC50 range 33.1–46.7 μg/mL. A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90–60% at 6 h, but this was low compared to benznidazole (50%. This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.

  15. 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...

  16. 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.

  17. Laboratory-based testing to evaluate abuse-deterrent formulations and satisfy the Food and Drug Administration's recommendation for Category 1 Testing.

    Science.gov (United States)

    Altomare, Christopher; Kinzler, Eric R; Buchhalter, August R; Cone, Edward J; Costantino, Anthony

    The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. Study protocols are designed to evaluate common abuse patterns of prescription medications as well as more advanced methods that have been reported on drug abuse websites and forums. Because FDA believes Category 1 testing should fully characterize the abuse-deterrent characteristics of an investigational formulation, Category 1 testing is time consuming and requires specialized laboratory resources as well as advanced knowledge of prescription medication abuse. Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of an investigational formulation. In this article, we will provide a general overview of the methods of manipulation and routes of administration commonly utilized by prescription drug abusers, how those methods and routes are evaluated in a laboratory setting, and discuss data intake, analysis, and reporting to satisfy FDA's Category 1 testing requirements.

  18. We really need to talk: adapting FDA processes to rapid change.

    Science.gov (United States)

    Lykken, Sara

    2013-01-01

    The rapidly evolving realm of modern commerce strains traditional regulatory paradigms. This paper traces the historical evolution of FDA crisis-response regulation and provides examples of ways in which the definitions and procedures resulting from that past continue to be challenged by new products as market entrants, some in good faith and others not, take actions that create disconnects between actual product and marketing controls and those that consumers might expect. The paper then explores some of the techniques used by other federal agencies that have faced similar challenges in environments characterized by rapid innovation, and draws from this analysis suggestions for improvement of the FDA's warning letter system.

  19. THPdb: Database of FDA-approved peptide and protein therapeutics.

    Directory of Open Access Journals (Sweden)

    Salman Sadullah Usmani

    Full Text Available THPdb (http://crdd.osdd.net/raghava/thpdb/ is a manually curated repository of Food and Drug Administration (FDA approved therapeutic peptides and proteins. The information in THPdb has been compiled from 985 research publications, 70 patents and other resources like DrugBank. The current version of the database holds a total of 852 entries, providing comprehensive information on 239 US-FDA approved therapeutic peptides and proteins and their 380 drug variants. The information on each peptide and protein includes their sequences, chemical properties, composition, disease area, mode of activity, physical appearance, category or pharmacological class, pharmacodynamics, route of administration, toxicity, target of activity, etc. In addition, we have annotated the structure of most of the protein and peptides. A number of user-friendly tools have been integrated to facilitate easy browsing and data analysis. To assist scientific community, a web interface and mobile App have also been developed.

  20. Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

    International Nuclear Information System (INIS)

    Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

    2012-01-01

    Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

  1. Proposed Objective Odor Control Test Methodology for Waste Containment

    Science.gov (United States)

    Vos, Gordon

    2010-01-01

    The Orion Cockpit Working Group has requested that an odor control testing methodology be proposed to evaluate the odor containment effectiveness of waste disposal bags to be flown on the Orion Crew Exploration Vehicle. As a standardized "odor containment" test does not appear to be a matter of record for the project, a new test method is being proposed. This method is based on existing test methods used in industrial hygiene for the evaluation of respirator fit in occupational settings, and takes into consideration peer reviewed documentation of human odor thresholds for standardized contaminates, industry stardnard atmostpheric testing methodologies, and established criteria for laboratory analysis. The proposed methodology is quantitative, though it can readily be complimented with a qualitative subjective assessment. Isoamyl acetate (IAA - also known at isopentyl acetate) is commonly used in respirator fit testing, and there are documented methodologies for both measuring its quantitative airborne concentrations. IAA is a clear, colorless liquid with a banana-like odor, documented detectable smell threshold for humans of 0.025 PPM, and a 15 PPB level of quantation limit.

  2. 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.

  3. Analysis of a proposed crucial test of quantum mechanics

    International Nuclear Information System (INIS)

    Collett, M.J.; Loudon, R.

    1987-01-01

    An experiment based on an extension of the Einstein-Podolsky-Rosen argument has been proposed by Popper as a crucial test of the Copenhagen interpretation of quantum mechanics. Here the authors show, by a slightly more complete version of Popper's analysis, although still at a relatively primitive level of sophistication, that the proposed experiment does not in fact provide such a test. (author)

  4. Commercialization of genetic testing services: the FDA, market forces, and biological tarot cards.

    Science.gov (United States)

    Malinowski, M J; Blatt, R J R

    1997-03-01

    Many women fear being diagnosed with breast cancer, and rightfully so. Despite the capabilities of modern medicine, the cumulative lifetime risk of getting the disease has risen to one in eight and, despite decades of research, no cures exist. In this Article, the authors explore the commercialization of so-called breast cancer gene tests, based upon genetic alterations linked to the disease. Although the authors fully address this specific technology, they use what constitutes the seminal case of predictive genetic testing to analyze the adequacy of the existing regulatory framework. The authors conclude that the present regulatory system is inadequate and places a dangerous amount of reliance on primary care physicians. Their conclusion is grounded in the observation that most primary care physicians lack sufficient knowledge about this evolving investigative technology--which is highly subject to misinterpretation, and, though potentially helpful to some "high risk" patients, offers questionable clinical value for the general public. The authors set forth numerous proposals to promote both the quality and clinical value of predictive genetic testing so that it conforms to public health standards and can be properly integrated as a reliable component of medical care in specific situations.

  5. Towards sensible toxicity testing for nanomaterials: proposal for the specification of test design

    International Nuclear Information System (INIS)

    Potthoff, Annegret; Meißner, Tobias; Weil, Mirco; Kühnel, Dana

    2015-01-01

    During the last decade, nanomaterials (NM) were extensively tested for potential harmful effects towards humans and environmental organisms. However, a sound hazard assessment was so far hampered by uncertainties and a low comparability of test results. The reason for the low comparability is a high variation in the (1) type of NM tested with regard to raw material, size and shape and (2) procedures before and during the toxicity testing. This calls for tailored, nanomaterial-specific protocols. Here, a structured approach is proposed, intended to lead to test protocols not only tailored to specific types of nanomaterials, but also to respective test system for toxicity testing. There are existing standards on single procedures involving nanomaterials, however, not all relevant procedures are covered by standards. Hence, our approach offers a detailed way of weighting several plausible alternatives for e.g. sample preparation, in order to decide on the procedure most meaningful for a specific nanomaterial and toxicity test. A framework of several decision trees (DT) and flow charts to support testing of NM is proposed as a basis for further refinement and in-depth elaboration. DT and flow charts were drafted for (1) general procedure—physicochemical characterisation, (2) choice of test media, (3) decision on test scenario and application of NM to liquid media, (4) application of NM to the gas phase, (5) application of NM to soil and sediments, (6) dose metrics, (S1) definition of a nanomaterial, and (S2) dissolution. The applicability of the proposed approach was surveyed by using experimental data retrieved from studies on nanoscale CuO. This survey demonstrated the DT and flow charts to be a convenient tool to systematically decide upon test procedures and processes, and hence pose an important step towards harmonisation of NM testing. (paper)

  6. Fisher, Neyman, and Bayes at FDA.

    Science.gov (United States)

    Rubin, Donald B

    2016-01-01

    The wise use of statistical ideas in practice essentially requires some Bayesian thinking, in contrast to the classical rigid frequentist dogma. This dogma too often has seemed to influence the applications of statistics, even at agencies like the FDA. Greg Campbell was one of the most important advocates there for more nuanced modes of thought, especially Bayesian statistics. Because two brilliant statisticians, Ronald Fisher and Jerzy Neyman, are often credited with instilling the traditional frequentist approach in current practice, I argue that both men were actually seeking very Bayesian answers, and neither would have endorsed the rigid application of their ideas.

  7. The teratology testing of food additives.

    Science.gov (United States)

    Barrow, Paul C; Spézia, François

    2013-01-01

    The developmental and reproductive toxicity testing (including teratogenicity) of new foods and food additives is performed worldwide according to the guidelines given in the FDA Redbook. These studies are not required for substances that are generally recognized as safe, according to the FDA inventory. The anticipated cumulated human exposure level above which developmental or reproduction studies are required depends on the structure-alert category. For food additives of concern, both developmental (prenatal) and reproduction (multigeneration) studies are required. The developmental studies are performed in two species, usually the rat and the rabbit. The reproduction study is generally performed in the rat. The two rat studies are preferably combined into a single experimental design, if possible. The test methods described in the FDA Redbook are similar to those specified by the OECD for the reproductive toxicity testing of chemicals.

  8. Three Drugs Approved for Urothelial Carcinoma by FDA.

    Science.gov (United States)

    2017-07-01

    The FDA has approved one PD-1 checkpoint inhibitor, pembrolizumab, and two PD-L1 checkpoint inhibitors, avelumab and durvalumab, to treat metastatic urothelial carcinoma in patients whose disease continues to progress despite platinum-based chemotherapy. This brings the total number of checkpoint inhibitors for the disease to five, prompting questions about how best to use them. ©2017 American Association for Cancer Research.

  9. Cost estimate for a proposed GDF Suez LNG testing program

    Energy Technology Data Exchange (ETDEWEB)

    Blanchat, Thomas K.; Brady, Patrick Dennis; Jernigan, Dann A.; Luketa, Anay Josephine; Nissen, Mark R.; Lopez, Carlos; Vermillion, Nancy; Hightower, Marion Michael

    2014-02-01

    At the request of GDF Suez, a Rough Order of Magnitude (ROM) cost estimate was prepared for the design, construction, testing, and data analysis for an experimental series of large-scale (Liquefied Natural Gas) LNG spills on land and water that would result in the largest pool fires and vapor dispersion events ever conducted. Due to the expected cost of this large, multi-year program, the authors utilized Sandia's structured cost estimating methodology. This methodology insures that the efforts identified can be performed for the cost proposed at a plus or minus 30 percent confidence. The scale of the LNG spill, fire, and vapor dispersion tests proposed by GDF could produce hazard distances and testing safety issues that need to be fully explored. Based on our evaluations, Sandia can utilize much of our existing fire testing infrastructure for the large fire tests and some small dispersion tests (with some modifications) in Albuquerque, but we propose to develop a new dispersion testing site at our remote test area in Nevada because of the large hazard distances. While this might impact some testing logistics, the safety aspects warrant this approach. In addition, we have included a proposal to study cryogenic liquid spills on water and subsequent vaporization in the presence of waves. Sandia is working with DOE on applications that provide infrastructure pertinent to wave production. We present an approach to conduct repeatable wave/spill interaction testing that could utilize such infrastructure.

  10. Understanding Laboratory Tests

    Science.gov (United States)

    ... and Drug Administration (FDA) regulates the development and marketing of all laboratory tests that use test kits ... Cancer.gov en español Multimedia Publications Site Map Digital Standards for NCI Websites POLICIES Accessibility Comment Policy ...

  11. 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

  12. 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.

  13. 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

  14. 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...

  15. 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

  16. [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.

  17. 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 ...

  18. 78 FR 78796 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products...

    Science.gov (United States)

    2013-12-27

    ... FDA's review of the change. The proposed rule published without a reference or a link to the... comments received, go to http://www.regulations.gov and insert the docket number(s), found in brackets in... rulemaking. The proposed rule published without reference or a link to the accompanying Regulatory Impact...

  19. 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.

  20. Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis: A Meta-Research Project.

    Directory of Open Access Journals (Sweden)

    Gil Amarilyo

    Full Text Available 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.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.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 odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy.FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34 except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61 pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55 pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical.There was no empirical evidence to suggest biased estimates between the two

  1. 76 FR 9024 - Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic...

    Science.gov (United States)

    2011-02-16

    ...] Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic Records; Electronic Signatures AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... relating to FDA's electronic records and electronic signatures. DATES: Submit either electronic or written...

  2. Proposal of world network on material testing reactors

    International Nuclear Information System (INIS)

    Takemoto, Noriyuki; Izumo, Hironobu; Hori, Naohiko; Ishitsuka, Etsuo; Ishihara, Masahiro

    2011-01-01

    Establishment of an international cooperation system of worldwide testing reactor network (world network) is proposed in order to achieve efficient facility utilization and provide high quality irradiation data by role sharing of irradiation tests with materials testing reactors in the world. As for the first step, mutual understanding among materials testing reactors is thought to be necessary. From this point, an international symposium on materials testing reactors (ISMTR) was held to construct the world network from 2008, and a common understanding of world network has begun to be shared. (author)

  3. Timelines of translational science: From technology initiation to FDA approval.

    Directory of Open Access Journals (Sweden)

    Laura M McNamee

    Full Text Available While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010-2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical trials, and 36 years to FDA approval. No products were approved before the established point, and development timelines were significantly longer when the clinical trials began before this point (11.5 vs 8.5 years, p<0.0005. Technological maturation represents the longest stage of translation, and significantly impacts the efficiency of drug development.

  4. 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.

  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. The FDA's failure to address the lack of generalisability of antidepressant efficacy trials in product labelling.

    Science.gov (United States)

    Zimmerman, Mark

    2016-06-01

    According to the US Food and Drug Administration's (FDA's) regulations, the criteria used to select patients into registration studies should be addressed in a product's label. The FDA's labelling guidelines, which specifically indicate that the routine exclusion of patients of a certain level of severity should be noted in the label, has been uniformly ignored. © The Royal College of Psychiatrists 2016.

  7. 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

  8. 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

  9. 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.

  10. Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population.

    Science.gov (United States)

    Yang, Tubao; Walker, Mark C; Krewski, Daniel; Yang, Qiuying; Nimrod, Carl; Garner, Peter; Fraser, William; Olatunbosun, Olufemi; Wen, Shi Wu

    2008-03-01

    To estimate the frequency of exposure to prescription Food and Drug Administration (FDA) category C, D, and X drugs in pregnant women, and to analyze the maternal characteristics associated with such an exposure. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 was chosen for the study. The rate of exposure to FDA category C, D, or X drugs recorded in the pharmacist database was estimated. Associations of exposure to FDA category C, D, and X drugs with maternal characteristics were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 575 women were included in this study. Among them, 3604 (19.4%) had exposure to one or more FDA category C, D, and X drugs during pregnancy. Category C drugs were the most frequently used drugs (15.8%), followed by D drugs (5.2%), and X drugs (3.9%). Women with chronic health conditions had fourfold at increased risk of exposure than women without. Regardless of health status, women who were or =3, and who were on social assistance plan were at increased risk of pregnancy exposure to these drugs. About 19.4% pregnant women are exposed to FDA C, D or X drugs during pregnancy. Women with chronic diseases, younger age, increased parity, and under social assistance are at increased risk of exposure to FDA C, D, or X drugs. Copyright 2008 John Wiley & Sons, Ltd.

  11. Evaluating three proposals for testing independence in non linear spatial processes

    OpenAIRE

    López Hernández, Fernando Antonio; Mate Sánchez-Val, María Luz; Artal Tur, Andrés

    2013-01-01

    [ENG]This paper evaluates the behaviour of different families of tests when checking for spatial independence in the presence of nonlinearities. To reach this goal, we select three representative proposals. The usual parametric tests of I-Moran, the nonparametric proposal of Brett and Pinkse (1997), and the semiparametric Scan test. In order to study how they perform, we simulate different nonlinear spatial structures by Monte Carlo methods, hence conducting empirical tests on ...

  12. 77 FR 29352 - Agency Information Collection Activities; Proposed Collection; Comment Request; Irradiation in...

    Science.gov (United States)

    2012-05-17

    ...] Agency Information Collection Activities; Proposed Collection; Comment Request; Irradiation in the... information collection provisions of FDA's requirements for food irradiation processors. DATES: Submit either... of information technology. Irradiation in the Production, Processing, and Handling of Food--21 CFR...

  13. 75 FR 12546 - Agency Information Collection Activities; Proposed Collection; Comment Request; Cosmetic Labeling...

    Science.gov (United States)

    2010-03-16

    ...] Agency Information Collection Activities; Proposed Collection; Comment Request; Cosmetic Labeling... FDA's cosmetic labeling regulations. DATES: Submit written or electronic comments on the collection of... of information technology. Cosmetic Labeling Regulations--21 CFR Part 701 (OMB Control Number 0910...

  14. 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.

  15. America, you are digging your grave with your spoon--should the FDA tell you that on food labels?

    Science.gov (United States)

    Card, Melissa M

    2013-01-01

    R.J. Reynolds Tobacco Co. v. Food & Drug Admin. discussed whether the FDA's promulgation of graphic images violated tobacco companies' First Amendment rights. While the tobacco companies contested the graphic images, the tobacco companies did not contest the promulgation of nine textual statements about the adverse effects of cigarettes. This uncontested mandate opens a door for the FDA to further expand its regulatory scheme. If the FDA can mandate textual statements about the adverse effects of cigarettes, can the FDA mandate textual statements about the adverse effects of sugar to combat the obesity crisis? This Article presents three textual statements about the adverse effects of sugar, to define the line between acceptable and unacceptable forms of compelled commercial speech under Central Hudson. Establishing this line ensures that the commercial speech doctrine does not deny the FDA from its authority to provide consumers with accurate information. While three textual statements are presented, this Article advocates that one of the textual statements is likely to serve as the best solution to the obesity crisis. The chosen textual statement serves as an effective solution because it presents meaningful information to the consumers enabling consumers to make healthful decisions about their food and encourages manufacturers to modify their products.

  16. 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

  17. Heparin crisis 2008: a tipping point for increased FDA enforcement in the pharma sector?

    Science.gov (United States)

    Rosania, Larry

    2010-01-01

    Against a backdrop of steady deregulation, the pharmaceutical industry is increasingly outsourcing manufacturing, resulting in decentralized control of the global supply chain. Established products such as heparin have been held to outdated analytical standards. Ten million Americans receive heparin every year; Baxter International accounts for half of this market. In 2008, contamination of Baxter's heparin--sourced in China--resulted in about 350 adverse events and 150 deaths in the United States. In future, increasingly stringent FDA inspections and enforcement are expected for imported drugs and ingredients. More regional FDA offices will be set up overseas. FDA funding will likely be supplemented in future by user fees charged to importers. For newer products, companies will face pressure to adopt Quality by Design, with solid control of the global supply chain and a proactive focus on GMP. Older products will be held to modern standards. Long-term, imports of drugs and ingredients from developing markets will continue. This makes sense to companies from an economic standpoint, but protections will be essential to ensure that it is also justifiable from a public health perspective.

  18. 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

  19. 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.

  20. 77 FR 18826 - Agency Information Collection Activities; Proposed Collection; Comment Request; Financial...

    Science.gov (United States)

    2012-03-28

    ... financial information to the sponsors of marketing applications. Under Sec. 54.4(a) (21 CFR 54.4(a... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0280] Agency Information Collection Activities; Proposed Collection; Comment Request; Financial Disclosure by...

  1. 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.

  2. Implementation and Test of the Automatic Flight Dynamics Operations for Geostationary Satellite Mission

    Directory of Open Access Journals (Sweden)

    Sangwook Park

    2009-12-01

    Full Text Available This paper describes the Flight Dynamics Automation (FDA system for COMS Flight Dynamics System (FDS and its test result in terms of the performance of the automation jobs. FDA controls the flight dynamics functions such as orbit determination, orbit prediction, event prediction, and fuel accounting. The designed FDA is independent from the specific characteristics which are defined by spacecraft manufacturer or specific satellite missions. Therefore, FDA could easily links its autonomous job control functions to any satellite mission control system with some interface modification. By adding autonomous system along with flight dynamics system, it decreases the operator’s tedious and repeated jobs but increase the usability and reliability of the system. Therefore, FDA is used to improve the completeness of whole mission control system’s quality. The FDA is applied to the real flight dynamics system of a geostationary satellite, COMS and the experimental test is performed. The experimental result shows the stability and reliability of the mission control operations through the automatic job control.

  3. Historical information on ORNL proposals for ECCS testing

    International Nuclear Information System (INIS)

    1976-01-01

    This document contains a compilation of the correspondence and preliminary report which the Oak Ridge National Laboratory submitted to the U.S. Atomic Energy Commission on the subject of in situ testing of emergency core cooling systems (ECCS) in pressurized water reactors. Most of the correspondence, which was prepared four to five years ago, deals with an ORNL proposal to evaluate the merits of conducting an in situ ECCS test in a full-scale commercial power plant. The end result of this work was to be a report in which the feasibility of conducting such an experiment would be discussed and a ''rough'' cost estimate provided. In support of this proposal, ORNL prepared a brief preliminary prospectus which identified some of the key questions that were to be addressed should the evaluation study be funded

  4. 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.

  5. 78 FR 57391 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food Canning...

    Science.gov (United States)

    2013-09-18

    ... data entry fields for the ``food product group'' (such as liquid, ready-to-eat ``breakfast foods''). We... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1119] Agency Information Collection Activities; Proposed Collection; Comment Request; Food Canning...

  6. 77 FR 8260 - Agency Information Collection Activities; Proposed Collection; Comment Request; Medical Device...

    Science.gov (United States)

    2012-02-14

    ... will be used to evaluate risks associated with medical devices which will enable FDA to take...] Agency Information Collection Activities; Proposed Collection; Comment Request; Medical Device Reporting... comment in response to the notice. This notice solicits comments on medical device reporting (MDR...

  7. 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.

  8. 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.

  9. 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

  10. 76 FR 61366 - Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to...

    Science.gov (United States)

    2011-10-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase...: Food and Drug Administration, HHS. [[Page 61367

  11. FDA Food Code recommendations: how do popular US baking shows measure up?

    Directory of Open Access Journals (Sweden)

    Valerie Cadorett

    2018-05-01

    Full Text Available The purpose of this study was to determine if popular US baking shows follow the FDA Food Code recommendations and critical food safety principles. This cross-sectional study examined a convenience sample of 75 episodes from three popular baking shows. The three shows were about competitively baking cupcakes, competitively baking cakes, and baking in a popular local bakery. Twenty-five episodes from each show were viewed. Coding involved tallying how many times 17 FDA Food Code recommendations were or were not followed. On each show, bare hands frequently came in contact with ready-to-eat food. On a per-hour basis, this occurred 80, 155, and 176 times on shows 1-3, respectively. Hands were washed before cooking three times on the three shows and never for the recommended 20 seconds. On each show, many people touched food while wearing jewelry other than a plain wedding band, for an average of at least 7 people per hour on each show. Shows 1-3 had high rates of long-haired bakers not wearing hair restraints (11.14, 6.57, and 14.06 per hour, respectively. Shows 1 and 2 had high rates of running among the bakers (22.29 and 10.57 instances per hour, respectively. These popular baking shows do not demonstrate proper food safety techniques put forth by the FDA and do not contribute the reduction of foodborne illnesses through proper food handling.

  12. FDA approves efavirenz. Food and Drug Administration.

    Science.gov (United States)

    Highleyman, L

    1998-10-01

    The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

  13. Mining association patterns of drug-interactions using post marketing FDA's spontaneous reporting data.

    Science.gov (United States)

    Ibrahim, Heba; Saad, Amr; Abdo, Amany; Sharaf Eldin, A

    2016-04-01

    Pharmacovigilance (PhV) is an important clinical activity with strong implications for population health and clinical research. The main goal of PhV is the timely detection of adverse drug events (ADEs) that are novel in their clinical nature, severity and/or frequency. Drug interactions (DI) pose an important problem in the development of new drugs and post marketing PhV that contribute to 6-30% of all unexpected ADEs. Therefore, the early detection of DI is vital. Spontaneous reporting systems (SRS) have served as the core data collection system for post marketing PhV since the 1960s. The main objective of our study was to particularly identify signals of DI from SRS. In addition, we are presenting an optimized tailored mining algorithm called "hybrid Apriori". The proposed algorithm is based on an optimized and modified association rule mining (ARM) approach. A hybrid Apriori algorithm has been applied to the SRS of the United States Food and Drug Administration's (U.S. FDA) adverse events reporting system (FAERS) in order to extract significant association patterns of drug interaction-adverse event (DIAE). We have assessed the resulting DIAEs qualitatively and quantitatively using two different triage features: a three-element taxonomy and three performance metrics. These features were applied on two random samples of 100 interacting and 100 non-interacting DIAE patterns. Additionally, we have employed logistic regression (LR) statistic method to quantify the magnitude and direction of interactions in order to test for confounding by co-medication in unknown interacting DIAE patterns. Hybrid Apriori extracted 2933 interacting DIAE patterns (including 1256 serious ones) and 530 non-interacting DIAE patterns. Referring to the current knowledge using four different reliable resources of DI, the results showed that the proposed method can extract signals of serious interacting DIAEs. Various association patterns could be identified based on the relationships among

  14. Lead-acid batteries in micro-hybrid applications. Part II. Test proposal

    Energy Technology Data Exchange (ETDEWEB)

    Schaeck, S.; Stoermer, A.O. [BMW Group, 80788 Muenchen (Germany); Albers, J. [Johnson Controls Power Solutions EMEA, 30419 Hannover (Germany); Weirather-Koestner, D. [ZSW Ulm, 89081 Ulm (Germany); Kabza, H. [Universitaet Ulm, Institut fuer Energiewandlung und -speicherung, 89081 Ulm (Germany)

    2011-02-01

    In the first part of this work selected key parameters for applying lead-acid (LA) batteries in micro-hybrid power systems (MHPS) were investigated. Main results are integrated in an accelerated, comprehensive test proposal presented here. The test proposal aims at a realistic representation of the pSoC operation regime, which is described in Refs. The test is designed to be sensitive with respect to dynamic charge acceptance (DCA) at partially discharged state (critical for regenerative braking) and the internal resistance at high-rate discharge (critical for idling stop applications). First results are presented for up-to-date valve-regulated LA batteries with absorbent glass mat (AGM) separators. The batteries are close to the limits of the first proposal of pass/fail-criteria. Also flooded batteries were tested; the first out of ten units failed already. (author)

  15. Lead-acid batteries in micro-hybrid applications. Part II. Test proposal

    Science.gov (United States)

    Schaeck, S.; Stoermer, A. O.; Albers, J.; Weirather-Koestner, D.; Kabza, H.

    In the first part of this work [1] selected key parameters for applying lead-acid (LA) batteries in micro-hybrid power systems (MHPS) were investigated. Main results are integrated in an accelerated, comprehensive test proposal presented here. The test proposal aims at a realistic representation of the pSoC operation regime, which is described in Refs. [1,6]. The test is designed to be sensitive with respect to dynamic charge acceptance (DCA) at partially discharged state (critical for regenerative braking) and the internal resistance at high-rate discharge (critical for idling stop applications). First results are presented for up-to-date valve-regulated LA batteries with absorbent glass mat (AGM) separators. The batteries are close to the limits of the first proposal of pass/fail-criteria. Also flooded batteries were tested; the first out of ten units failed already.

  16. 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.

  17. Year 2000 (Y2K) computer compliance guide; guidance for FDA personnel. Food and Drug Administration. Notice.

    Science.gov (United States)

    1999-05-14

    The Food and Drug Administration (FDA) is announcing the availability of a new compliance policy guide (CPG) entitled "Year 2000 (Y2K) Computer Compliance" (section 160-800). This guidance document represents the agency's current thinking on the manufacturing and distribution of domestic and imported products regulated by FDA using computer systems that may not perform properly before, or during, the transition to the year 2000 (Y2K). The text of the CPG is included in this notice. This compliance guidance document is an update to the Compliance Policy Guides Manual (August 1996 edition). It is a new CPG, and it will be included in the next printing of the Compliance Policy Guides Manual. This CPG is intended for FDA personnel, and it is available electronically to the public.

  18. Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

    Science.gov (United States)

    Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

    2017-01-01

    Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

  19. 77 FR 8879 - Agency Information Collection Activities; Proposed Collection; Comment Request: Guidance for...

    Science.gov (United States)

    2012-02-15

    ... report will alert FDA to trends or clusters of events that might be a safety issue otherwise unreported...] Agency Information Collection Activities; Proposed Collection; Comment Request: Guidance for Industry and... of information technology. Guidance for Industry and Food and Drug Administration Staff; Class II...

  20. FDA & digital mammography: why has FDA required full field digital mammography systems to be regulated as potentially dangerous devices for more than 10 years?

    Science.gov (United States)

    Nields, Morgan W

    2010-05-01

    Digital mammography is routinely used in the US to screen asymptomatic women for breast cancer and currently over 50% of US screening centers employ the technology. In spite of FDAs knowledge that digital mammography requires less radiation than film mammography and that its equivalence has been proven in a prospective randomized trial, the agency has failed to allow the technology market access via the 510(k) pre market clearance pathway. As a result of the restrictive Pre Market Approval process, only four suppliers have received FDA approval. The resulting lack of a competitive market has kept costs high, restricted technological innovation, and impeded product improvements as a result of PMA requirements. Meanwhile, at least twelve companies are on the market in the EU and the resulting competitive market has lowered costs and provided increased technological choice. A cultural change with new leadership occurred in the early 90's at FDA. The historical culture at the Center for Devices and Radiological Health of collaboration and education gave way to one characterized by a lack of reliance on outside scientific expertise, tolerance of decision making by unqualified reviewers, and an emphasis on enforcement and punishment. Digital mammography fell victim to this cultural change and as a result major innovations like breast CT and computer aided detection technologies are also withheld from the market. The medical device law, currently under review by the Institute of Medicine, should be amended by the Congress so that new technologies can be appropriately classified in accordance with the risk based assessment classification system detailed in Chapter V of the Federal Food, Drug, and Cosmetic Act. A panel of scientific experts chartered by the NIH or IOM should determine the classification appropriate for new technologies that have no historical regulatory framework. This would be binding on FDA. Unless the law is changed we will likely again experience

  1. 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.

  2. 76 FR 1168 - Agency Information Collection Activities; Proposed Collection; Comment Request; Health and Diet...

    Science.gov (United States)

    2011-01-07

    ... Supplement will include: (1) Awareness and sources of information, (2) attitudes toward diet and physical... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0001] Agency Information Collection Activities; Proposed Collection; Comment Request; Health and Diet Survey...

  3. 77 FR 69630 - Agency Information Collection Activities; Proposed Collection; Comment Request; New Animal Drug...

    Science.gov (United States)

    2012-11-20

    ... must be assembled and submitted. The application must include safety and effectiveness data, proposed labeling, product manufacturing information, and where necessary, complete information on food safety... Applications and Supporting Regulations, and Form FDA 356V AGENCY: Food and Drug Administration, HHS. ACTION...

  4. Language and Nutrition (Mis)Information: Food Labels, FDA Policies and Meaning

    Science.gov (United States)

    Taylor, Christy Marie

    2013-01-01

    In this dissertation, I address the ways in which food manufacturers can exploit the often vague and ambiguous nature of FDA policies concerning language and images used on food labels. Employing qualitative analysis methods (Strauss, 1987; Denzin and Lincoln, 2003; Mackey and Gass, 2005) that drew upon critical discourse analysis (Fairclough,…

  5. 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... committee: (1) The committee shall give public notice of its meetings and agenda, and provide interested...

  6. 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

  7. 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

  8. 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

  9. A proposed standard round compact specimen for plane strain fracture toughness testing

    Science.gov (United States)

    Underwood, J. H.; Newman, J. C., Jr.; Seeley, R. R.

    1980-01-01

    A round, disk-shaped specimen is proposed as a standard test specimen for addition to ASTM Test for Plane-Strain Fracture Toughness of Metallic Materials (E 399-78A). The specimen is diametrically cracked, and loaded in the same way as the existing standard compact specimen. Tests and analyses were performed to verify that the proposed round compact specimen and associated stress intensity factor K solution are appropriate for a standard plane strain fracture toughness test. The use of the round compact specimen for other fracture tests is described.

  10. Putting New Laboratory Tests Into Practice

    Science.gov (United States)

    ... some patients may have to pay out-of-pocket for these tests. Non-FDA approved tests are ... view/article/4775/. Accessed October 2016. The Free Dictionary. Class III device. Available online at http://medical- ...

  11. A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Fu-Shun Hsu

    2017-01-01

    Full Text Available Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

  12. 75 FR 47599 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generic Food and...

    Science.gov (United States)

    2010-08-06

    ... frequency of response was determined by the maximum number of questionnaires that will be sent to any... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0380] Agency Information Collection Activities; Proposed Collection; Comment Request; Generic Food and Drug...

  13. 77 FR 8880 - Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing...

    Science.gov (United States)

    2012-02-15

    ... Competition and Innovation Act of 2009 (BPCI Act) which amends the Public Health Service Act (PHS Act) and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1029... product and an application for a supplement for a proposed interchangeable product. DATES: Submit either...

  14. Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans-

    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.

  15. 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

  16. A proposed test for the determination of the grindability of fine materials

    International Nuclear Information System (INIS)

    Levin, J.

    1984-01-01

    The grindability of ores is generally determined by the Bond standard grindability test. However, this test is not applicable to fine matetials such as sands; the grindability of fine materials must therefore be determined by a comparative grinding method, for which a reference material of known grindability is required. Suitable reference materials are not easily obtained, and a grindability test that does not depend on reference materials is needed. This report proposes such a test and records the results of some tests on the validity of the proposed method. The proposed grindability test uses the Bond standard test mill and a quantity called the 'equivalent energy per minute', which is the energy per minute that would be used by the mill if it were scaled up to a wet-grinding industrial mill of 2,44m (8 ft) diameter. The value of this quantity, denoted by E, was calculated from the results of Bond standard grindability test on various materials, and an average value of 1425X10- 6 kW.h/min was determined. It is suggested that values far removed from this figure indicate that the ores concerned do not conform to the Bond Law of Comminution. The proposed grindability test was applied to seven samples of ore from industrial secondary grinding mills and to one sample of sand, and good agreement was found between the energy consumption calculated in the laboratory tests and those reported for the operating plants. The energy consumption calculated from the results of the Bond standard grindability test agreed fairly well with the plant data for the secondary grinding circuits, but the correlation for the primary grinding circuit was erratic

  17. 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...

  18. 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.

  19. Stem-cell-derived products: an FDA update.

    Science.gov (United States)

    Moos, Malcolm

    2008-12-01

    The therapeutic potential of products derived from stem cells of various types has prompted increasing research and development and public attention. Initiation of human clinical trials in the not-too-distant future is now a realistic possibility. It is, therefore, important to weigh the potential benefits against known, theoretical and totally unsuspected risks in light of current knowledge to ensure that subjects participating in these trials are afforded the most reasonable balance possible between potential risks and potential benefits. There are no apparent differences in fundamental, qualitative biological characteristics between stem-cell-derived products and other cellular therapies regulated by the United States Food and Drug Administration (FDA). Existing authorities can, therefore, be applied. Nevertheless, these products do have properties that require careful evaluation.

  20. Evaluating the Impact of U.S. Food and Drug Administration-Proposed Nutrition Facts Label Changes on Young Adults' Visual Attention and Purchase Intentions.

    Science.gov (United States)

    Graham, Dan J; Roberto, Christina A

    2016-08-01

    The U.S. Food and Drug Administration (FDA) has proposed modifying the Nutrition Facts Label (NFL) on food packages to increase consumer attention to this resource and to promote healthier dietary choices. The present study sought to determine whether the proposed NFL changes will affect consumer attention to the NFL or purchase intentions. This study compared purchase intentions (yes/no responses to "would you purchase this food?" for 64 products) and attention to NFLs (measured via high-speed eye-tracking camera) among 155 young adults randomly assigned to view products with existing versus modified NFLs. Attention to all individual components of the NFL (e.g., calories, fats, sugars) were analyzed separately to assess the impact of each proposed NFL modification on attention to that region. Data were collected in 2014; analysis was conducted in 2015. Modified NFLs did not elicit significantly more visual attention or lead to more healthful purchase intentions than did existing NFLs. Relocating the percent daily value component from the right side of the NFL to the left side, as proposed by the FDA, actually reduced participants' attention to this information. The proposed "added sugars" component was viewed on at least one label by a majority (58%) of participants. Results suggest that the proposed NFL changes may not achieve FDA's goals. Changes to nutrition labeling may need to take a different form to meaningfully influence dietary behavior. Young adults' visual attention and purchase intentions do not appear to be meaningfully affected by the proposed NFL modifications. © 2016 Society for Public Health Education.

  1. 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.

  2. 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.

  3. Medical devices: reports of corrections and removals; delay of effective data--FDA. Direct final rule; delay of effective date.

    Science.gov (United States)

    1998-11-18

    The Food and Drug Administration (FDA) published in the Federal Register of August 7, 1998 (63 FR 42229), a direct final rule. The direct final rule notified the public of FDA's intention to amend the regulations that govern reports of corrections and removals of medical devices to eliminate the requirement for distributors to make such reports. This document delays the effective date of the direct final rule.

  4. 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

  5. Testing consumer perception of nutrient content claims using conjoint analysis.

    Science.gov (United States)

    Drewnowski, Adam; Moskowitz, Howard; Reisner, Michele; Krieger, Bert

    2010-05-01

    The US Food and Drug Administration (FDA) proposes to establish standardized and mandatory criteria upon which front-of-pack (FOP) nutrition labelling must be based. The present study aimed to estimate the relative contribution of declared amounts of different nutrients to the perception of the overall 'healthfulness' of foods by the consumer. Protein, fibre, vitamin A, vitamin C, calcium and iron were nutrients to encourage. Total fat, saturated fat, cholesterol, total and added sugar, and sodium were the nutrients to limit. Two content claims per nutrient used the FDA-approved language. An online consumer panel (n 320) exposed to multiple messages (n 48) rated the healthfulness of each hypothetical food product. Utility functions were constructed using conjoint analysis, based on multiple logistic regression and maximum likelihood estimation. Consumer perception of healthfulness was most strongly driven by the declared presence of protein, fibre, calcium and vitamin C and by the declared total absence of saturated fat and sodium. For this adult panel, total and added sugar had lower utilities and contributed less to the perception of healthfulness. There were major differences between women and men. Conjoint analysis can lead to a better understanding of how consumers process information about the full nutrition profile of a product, and is a powerful tool for the testing of nutrient content claims. Such studies can help the FDA develop science-based criteria for nutrient profiling that underlies FOP and shelf labelling.

  6. 75 FR 8963 - Agency Information Collection Activities; Proposed Collection; Comment Request; Reporting and...

    Science.gov (United States)

    2010-02-26

    ..., including each proposed extension of an existing collection of information, and to allow 60 days for public...)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day notice in... Vapor Lamp Products Radiation Safety Report'' FDA Form 3647 ``Guide for Preparing Annual Reports on...

  7. Proposed experimental test of an alternative electrodynamic theory of superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Hirsch, J.E., E-mail: jhirsch@ucsd.edu

    2015-01-15

    Highlights: • A new experimental test of electric screening in superconductors is proposed. • The electric screening length is predicted to be much larger than in normal metals. • The reason this was not seen in earlier experiments is explained. • This is not predicted by the conventional BCS theory of superconductivity. - Abstract: An alternative form of London’s electrodynamic theory of superconductors predicts that the electrostatic screening length is the same as the magnetic penetration depth. We argue that experiments performed to date do not rule out this alternative formulation and propose an experiment to test it. Experimental evidence in its favor would have fundamental implications for the understanding of superconductivity.

  8. Association between change of health care providers and pregnancy exposure to FDA category C, D and X drugs.

    Science.gov (United States)

    Yang, Jianzhou; Xie, Rihua; Krewski, Daniel; Wang, Yongjin; Walker, Mark; Cao, Wenjun; Wen, Shi Wu

    2014-01-01

    Changing health care providers frequently breaks the continuity of care, which is associated with many health care problems. The purpose of this study was to examine the association between a change of health care providers and pregnancy exposure to FDA category C, D and X drugs. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 were chosen for this study. The association between the number of changes in health care providers and with pregnancy exposure to category C, D, and X drugs for those women with and without chronic diseases were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 568 women were included in this study. Rates of FDA C, D, and X drug uses were 14.35%, 17.07%, 21.72%, and 31.14%, in women with no change of provider, 1-2 changes, 3-5 changes, and more than 5 changes of health care providers. An association between the number of changes of health care providers and pregnancy exposure to FDA C, D, and X drugs existed in women without chronic diseases but not in women with chronic disease. Change of health care providers is associated with pregnancy exposure to FDA category C, D and X drugs in women without chronic diseases.

  9. 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

    2018-04-01

    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 according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p 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.

  10. Spurious Seasonality Detection: A Non-Parametric Test Proposal

    Directory of Open Access Journals (Sweden)

    Aurelio F. Bariviera

    2018-01-01

    Full Text Available This paper offers a general and comprehensive definition of the day-of-the-week effect. Using symbolic dynamics, we develop a unique test based on ordinal patterns in order to detect it. This test uncovers the fact that the so-called “day-of-the-week” effect is partly an artifact of the hidden correlation structure of the data. We present simulations based on artificial time series as well. While time series generated with long memory are prone to exhibit daily seasonality, pure white noise signals exhibit no pattern preference. Since ours is a non-parametric test, it requires no assumptions about the distribution of returns, so that it could be a practical alternative to conventional econometric tests. We also made an exhaustive application of the here-proposed technique to 83 stock indexes around the world. Finally, the paper highlights the relevance of symbolic analysis in economic time series studies.

  11. GENIUS-TF - a test facility for the GENIUS project. Proposal

    International Nuclear Information System (INIS)

    Klapdor-Kleingrothaus, H.V.; Dietz, A.; Heusser, G.

    2001-02-01

    GENIUS is a proposal for a large scale detector of rare events. As a first step of the experiment, a small test version, the Genius Test-Facility is proposed to be built up at the Laboratori Nazionali del Gran Sasso (LNGS). With about 40 kg of natural Ge detectors operated in liquid nitrogen, Genius-TF could exclude (or directly confirm) the DAMA annual modulation signature within about two years of measurement using both, signal and signature of the claimed WIMP Dark matter. The funding of the experiment has already been approved and four 2.5 kg germanium detectors with an extreme low treshold of 500 eV have been produced. The installation can be started immediately. No additional space in the Underground Laboratory is required. (orig.)

  12. New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

    Science.gov (United States)

    English, Clayton; Aloi, Joseph J

    2015-04-01

    Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients

  13. Proposed sealing field tests for a potential high-level radioactive waste repository in unsaturated tuff

    International Nuclear Information System (INIS)

    Fernandez, J.A.; Case, J.B.; Tyburski, J.

    1992-01-01

    This paper contains a general description of the field tests proposed for the Yucca Mountain Site Characterization Project repository sealing program. The tests are intended to resolve various performance and emplacement concerns associated with sealing components. Ten discrete tests are proposed to address these concerns. These tests are divided into two categories -- simple and complex tests. The simple tests are: the small-scale in situ tests: the intermediate-scale borehole seal tests; the fracture grouting tests; the surface backfill tests; and the grouted rock mass tests. The complex tests are the seepage control tests; in situ backfill tests; in situ bulkhead tests; large-scale shaft seal tests; and remote borehole seal tests. These tests are proposed to be performed in welded and nonwelded tuff environments. The final selection of sealing tests will depend on the nature of the geologic and hydrologic conditions encountered during the development of the exploratory studies facility. Some tests may be performed before license application and some after license application

  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. Dissolution comparisons using a Multivariate Statistical Distance (MSD) test and a comparison of various approaches for calculating the measurements of dissolution profile comparison.

    Science.gov (United States)

    Cardot, J-M; Roudier, B; Schütz, H

    2017-07-01

    The f 2 test is generally used for comparing dissolution profiles. In cases of high variability, the f 2 test is not applicable, and the Multivariate Statistical Distance (MSD) test is frequently proposed as an alternative by the FDA and EMA. The guidelines provide only general recommendations. MSD tests can be performed either on raw data with or without time as a variable or on parameters of models. In addition, data can be limited-as in the case of the f 2 test-to dissolutions of up to 85% or to all available data. In the context of the present paper, the recommended calculation included all raw dissolution data up to the first point greater than 85% as a variable-without the various times as parameters. The proposed MSD overcomes several drawbacks found in other methods.

  16. Proposed waste form performance criteria and testing methods for low-level mixed waste

    International Nuclear Information System (INIS)

    Franz, E.M.; Fuhrmann, M.; Bowerman, B.; Bates, S.; Peters, R.

    1994-08-01

    This document describes proposed waste form performance criteria and testing method that could be used as guidance in judging viability of a waste form as a physico-chemical barrier to releases of radionuclides and RCRA regulated hazardous components. It is assumed that release of contaminants by leaching is the single most important property by which the effectiveness of a waste form is judged. A two-tier regimen is proposed. The first tier includes a leach test required by the Environmental Protection Agency and a leach test designed to determine the net forward leach rate for a variety of materials. The second tier of tests are to determine if a set of stresses (i.e., radiation, freeze-thaw, wet-dry cycling) on the waste form adversely impact its ability to retain contaminants and remain physically intact. It is recommended that the first tier tests be performed first to determine acceptability. Only on passing the given specifications for the leach tests should other tests be performed. In the absence of site-specific performance assessments (PA), two generic modeling exercises are described which were used to calculate proposed acceptable leach rates

  17. FDA direct-to-consumer advertising for prescription drugs: what are consumer preferences and response tendencies?

    Science.gov (United States)

    Khanfar, Nile; Loudon, David; Sircar-Ramsewak, Feroza

    2007-01-01

    The effect of direct-to-consumer (DTC) television advertising of prescription medications is a growing concern of the United States (U.S.) Congress, state legislatures, and the Food and Drug Administration (FDA). This research study was conducted in order to examine consumers' perceived preferences of DTC television advertisement in relation to "reminder" "help-seeking," and "product-claim" FDA-approved advertisement categories. An additional objective was to examine the influence of DTC television advertising of prescription drugs on consumers' tendency to seek more information about the medication and/or the medical condition. The research indicates that DTC television drug ads appear to be insufficient for consumers to make informed decisions. Their mixed perception and acceptance of the advertisements seem to influence them to seek more information from a variety of medical sources.

  18. The US FDA and animal cloning: risk and regulatory approach.

    Science.gov (United States)

    Rudenko, Larisa; Matheson, John C

    2007-01-01

    The Food and Drug Administration's (FDA's) Center for Veterinary Medicine issued a voluntary request to producers of livestock clones not to introduce food from clones or their progeny into commerce until the agency had assessed whether production of cattle, swine, sheep, or goats by somatic cell nuclear transfer (SCNT) posed any unique risks to the animal(s) involved in the process, humans, or other animals by consuming food from those animals, compared with any other assisted reproductive technology (ART) currently in use. Following a comprehensive review, no anomalies were observed in animals produced by cloning that have not also been observed in animals produced by other ARTs and natural mating. Further systematic review on the health of, and composition of meat and milk from, cattle, swine, and goat clones and the progeny of cattle and sheep did not result in the identification of any food-consumption hazards. The agency therefore concluded that food from cattle, swine, and goat clones was as safe to eat as food from animals of those species derived by conventional means. The agency also concluded that food from the progeny of the clone of any species normally consumed for food is as safe to eat as those animals. The article also describes the methodology used by the agency to analyze data and draw these conclusions, the plans the agency has proposed to manage any identified risks, and the risk communication approaches the agency has used.

  19. 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...

  20. 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.; Ma, Xiaohua; Miao, Xiaohe; Pinnau, Ingo

    2017-01-01

    ,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 (6

  1. 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

  2. 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

  3. What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?

    Science.gov (United States)

    de Leon, Jose; Spina, Edoardo

    2016-01-01

    This editorial considers two questions in psychopharmacotherapy: 1) What is needed to market pharmacogenetic tests in the US, since the US appears to lead other countries? and 2) What is needed for US-marketed pharmacogenetic tests to be incorporated by prescribers into long-term practice? US marketing of pharmacogenetic tests requires 1) understanding the pharmacological complexity of drug response, 2) modifying the oversight of non-FDA regulatory agencies, 3) clarifying the FDA's role and 4) promoting innovative marketing. The incorporation of pharmacogenetic tests into long-term practice requires 1) not jeopardizing pharmacogenetic testing by short-sighted marketing of non-validated tests, 2) educating prescribers about benefits, 3) educating patients about limitations and 4) considering the differences between isolated testing and generalized testing incorporating big data.

  4. Proposed waste form performance criteria and testing methods for low-level mixed waste

    International Nuclear Information System (INIS)

    Franz, E.M.; Fuhrmann, M.; Bowerman, B.

    1995-01-01

    Proposed waste form performance criteria and testing methods were developed as guidance in judging the suitability of solidified waste as a physico-chemical barrier to releases of radionuclides and RCRA regulated hazardous components. The criteria follow from the assumption that release of contaminants by leaching is the single most important property for judging the effectiveness of a waste form. A two-tier regimen is proposed. The first tier consists of a leach test designed to determine the net, forward leach rate of the solidified waste and a leach test required by the Environmental Protection Agency (EPA). The second tier of tests is to determine if a set of stresses (i.e., radiation, freeze-thaw, wet-dry cycling) on the waste form adversely impacts its ability to retain contaminants and remain physically intact. In the absence of site-specific performance assessments (PA), two generic modeling exercises are described which were used to calculate proposed acceptable leachates

  5. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

    Science.gov (United States)

    Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

    2012-01-01

    Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

  6. 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

  7. Proposals for cold testing of the ITER TF coils

    International Nuclear Information System (INIS)

    Libeyre, P.; Ciazynski, D.; Dolgetta, N.; Duchateau, J.L.; Lyraud, C.; Kircher, F.; Schild, T.; Fietz, W.H.; Zahn, G.

    2005-01-01

    The ITER Toroidal Field (TF) magnet system will be made of 18 coils using Nb 3 Sn as superconducting material. These coils will operate at a maximum field of 11.8 T for a nominal current of 68 kA carried by a dual channel cable-in-conduit conductor cooled by a forced flow of supercritical helium at 4.5 K. In each coil, seven 760 m conductor lengths wound in double pancakes will be connected to each other by low resistance joints. As a final step of the reception tests, it is proposed to perform cold tests of these coils at liquid helium temperature after completion of their manufacture. The testing shall include high voltage tests to check the quality of the insulation, leak tests and pressure drop measurements of the hydraulic circuits as well as measurement of the joint resistances. Testing the coils up to nominal current is a discussed option, addressing on one hand measurement of the electrical performances in self field and on the other hand the mechanical behaviour of the coils. To perform these tests, a dedicated test facility has to be built, allowing possible simultaneous testing of two coils, assembled together in a twin coil configuration, similarly to their assembly in the torus. (authors)

  8. Proposals for cold testing of the ITER TF coils

    Energy Technology Data Exchange (ETDEWEB)

    Libeyre, P.; Ciazynski, D.; Dolgetta, N.; Duchateau, J.L.; Lyraud, C. [Association Euratom/CEA Cadarache, Dept. de Recherches sur la Fusion Controlee (DRFC), 13 - Saint-Paul-lez-Durance (France); Kircher, F.; Schild, T. [CEA Saclay, Dept. d' Astrophysique, de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, 91- Gif sur Yvette (France); Fietz, W.H.; Zahn, G. [Association Euratom-Forschungszentrum Karlsruhe, Karlsruhe (Germany)

    2005-07-01

    The ITER Toroidal Field (TF) magnet system will be made of 18 coils using Nb{sub 3}Sn as superconducting material. These coils will operate at a maximum field of 11.8 T for a nominal current of 68 kA carried by a dual channel cable-in-conduit conductor cooled by a forced flow of supercritical helium at 4.5 K. In each coil, seven 760 m conductor lengths wound in double pancakes will be connected to each other by low resistance joints. As a final step of the reception tests, it is proposed to perform cold tests of these coils at liquid helium temperature after completion of their manufacture. The testing shall include high voltage tests to check the quality of the insulation, leak tests and pressure drop measurements of the hydraulic circuits as well as measurement of the joint resistances. Testing the coils up to nominal current is a discussed option, addressing on one hand measurement of the electrical performances in self field and on the other hand the mechanical behaviour of the coils. To perform these tests, a dedicated test facility has to be built, allowing possible simultaneous testing of two coils, assembled together in a twin coil configuration, similarly to their assembly in the torus. (authors)

  9. The evolution of FDA policy on silicone breast implants: a case study of politics, bureaucracy, and business in the process of decision-making.

    Science.gov (United States)

    Palley, H A

    1995-01-01

    The central issue facing federal regulation of breast implants is that while such devices are not functionally necessary or needed for survival, the side effects may be harmful and have not been proven unharmful. The Medical Device Amendments of 1976 appear to require such evidence prior to the FDA permitting the unrestricted marketing of these devices. However, only recently have such requirements been imposed by the FDA. The author examines the FDA's decision-making process, particularly as applied to silicone breast implants, and the factors that appears to have affected such decisions. In pursuing this study, the activities of a number of interest-group actors, as well as congressional responses and the role of federal bureaucratic actors, were examined. In 1992, the FDA established a regulatory protocol that effectively withdrew most silicone breast implants from the market for the purpose of breast augmentation and allows for the monitoring of the impact of new implants on women's health. This increase concern for determining the safety of breast implants is due to a number of factors, which are examined in this article.

  10. Evaluating the Impact of U.S. Food and Drug Administration-Proposed Nutrition Facts Label Changes on Young Adults' Visual Attention and Purchase Intentions

    Science.gov (United States)

    Graham, Dan J.; Roberto, Christina A.

    2016-01-01

    Background: The U.S. Food and Drug Administration (FDA) has proposed modifying the Nutrition Facts Label (NFL) on food packages to increase consumer attention to this resource and to promote healthier dietary choices. Aims: The present study sought to determine whether the proposed NFL changes will affect consumer attention to the NFL or purchase…

  11. 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...

  12. 21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee on the initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... technical advisory committee for human prescription drugs. The Commissioner's determinations on the agenda...

  13. Water table tests of proposed heat transfer tunnels for small turbine vanes

    Science.gov (United States)

    Meitner, P. L.

    1974-01-01

    Water-table flow tests were conducted for proposed heat-transfer tunnels which were designed to provide uniform flow into their respective test sections of a single core engine turbine vane and a full annular ring of helicopter turbine vanes. Water-table tests were also performed for the single-vane test section of the core engine tunnel. The flow in the heat-transfer tunnels was shown to be acceptable.

  14. Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans.

    Science.gov (United States)

    Díaz-Sánchez, Ángel Gabriel; Alvarez-Parrilla, Emilio; Martínez-Martínez, Alejandro; Aguirre-Reyes, Luis; Orozpe-Olvera, Jesica Aline; Ramos-Soto, Miguel Armando; Núñez-Gastélum, José Alberto; Alvarado-Tenorio, Bonifacio; de la Rosa, Laura Alejandra

    2016-11-26

    Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2'-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a "hinge" located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity.

  15. 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

  16. 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...

  17. 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

  18. 76 FR 36019 - Amendments to Sterility Test Requirements for Biological Products

    Science.gov (United States)

    2011-06-21

    ... the biologics regulations. DATES: Submit either electronic or written comments on this proposed rule... No. FDA-2011- N-0080, by any of the following methods: Electronic Submissions Submit electronic... Factor (AHF), Platelets, Red Blood Cells, Plasma, Source Plasma, Smallpox Vaccine, Reagent Red Blood...

  19. Proposal and validation of a clinical trunk control test in individuals with spinal cord injury.

    Science.gov (United States)

    Quinzaños, J; Villa, A R; Flores, A A; Pérez, R

    2014-06-01

    One of the problems that arise in spinal cord injury (SCI) is alteration in trunk control. Despite the need for standardized scales, these do not exist for evaluating trunk control in SCI. To propose and validate a trunk control test in individuals with SCI. National Institute of Rehabilitation, Mexico. The test was developed and later evaluated for reliability and criteria, content, and construct validity. We carried out 531 tests on 177 patients and found high inter- and intra-rater reliability. In terms of criterion validity, analysis of variance demonstrated a statistically significant difference in the test score of patients with adequate or inadequate trunk control according to the assessment of a group of experts. A receiver operating characteristic curve was plotted for optimizing the instrument's cutoff point, which was determined at 13 points, with a sensitivity of 98% and a specificity of 92.2%. With regard to construct validity, the correlation between the proposed test and the spinal cord independence measure (SCIM) was 0.873 (P=0.001) and that with the evolution time was 0.437 (P=0.001). For testing the hypothesis with qualitative variables, the Kruskal-Wallis test was performed, which resulted in a statistically significant difference between the scores in the proposed scale of each group defined by these variables. It was proven experimentally that the proposed trunk control test is valid and reliable. Furthermore, the test can be used for all patients with SCI despite the type and level of injury.

  20. New experimental proposals for testing Dirac equation

    International Nuclear Information System (INIS)

    Camacho, Abel; Macias, Alfredo

    2004-01-01

    The advent of phenomenological quantum gravity has ushered us in the search for experimental tests of the deviations from general relativity predicted by quantum gravity or by string theories, and as a by-product of this quest the possible modifications that some field equations, for instance, the motion equation of spin-1/2-particles, have already been considered. In the present Letter a modified Dirac equation, whose extra term embraces a second-order time derivative, is taken as mainstay, and three different experimental proposals to detect it are put forward. The novelty in these ideas is that two of them do not fall within the extant approaches in this context, to wit, red-shift, atomic interferometry, or Hughes-Drever type-like experiments

  1. FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    de Claro, R Angelo; McGinn, Karen M; Verdun, Nicole; Lee, Shwu-Luan; Chiu, Haw-Jyh; Saber, Haleh; Brower, Margaret E; Chang, C J George; Pfuma, Elimika; Habtemariam, Bahru; Bullock, Julie; Wang, Yun; Nie, Lei; Chen, Xiao-Hong; Lu, Donghao Robert; Al-Hakim, Ali; Kane, Robert C; Kaminskas, Edvardas; Justice, Robert; Farrell, Ann T; Pazdur, Richard

    2015-08-15

    On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. ©2015 American Association for Cancer Research.

  2. Comment on a proposed ''crucial experiment'' to test Einstein's special theory of relativity

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Jr, W A [Universidade Estadual de Campinas (Brazil); Buonamano, V [Universidade Estadual de Campinas (Brazil). Instituto de Matematica

    1976-08-11

    A proposed ''crucial experiment'' to test Einstein's special theory of relativity is analysed and it is shown that it falls into the set of unsatisfactory proposals that attempt to make an experimental distinction between Einstein's special theory of relativity and a ''Lorentzian type'' special theory of relativity.

  3. Equivalence Testing of Complex Particle Size Distribution Profiles Based on Earth Mover's Distance.

    Science.gov (United States)

    Hu, Meng; Jiang, Xiaohui; Absar, Mohammad; Choi, Stephanie; Kozak, Darby; Shen, Meiyu; Weng, Yu-Ting; Zhao, Liang; Lionberger, Robert

    2018-04-12

    Particle size distribution (PSD) is an important property of particulates in drug products. In the evaluation of generic drug products formulated as suspensions, emulsions, and liposomes, the PSD comparisons between a test product and the branded product can provide useful information regarding in vitro and in vivo performance. Historically, the FDA has recommended the population bioequivalence (PBE) statistical approach to compare the PSD descriptors D50 and SPAN from test and reference products to support product equivalence. In this study, the earth mover's distance (EMD) is proposed as a new metric for comparing PSD particularly when the PSD profile exhibits complex distribution (e.g., multiple peaks) that is not accurately described by the D50 and SPAN descriptor. EMD is a statistical metric that measures the discrepancy (distance) between size distribution profiles without a prior assumption of the distribution. PBE is then adopted to perform statistical test to establish equivalence based on the calculated EMD distances. Simulations show that proposed EMD-based approach is effective in comparing test and reference profiles for equivalence testing and is superior compared to commonly used distance measures, e.g., Euclidean and Kolmogorov-Smirnov distances. The proposed approach was demonstrated by evaluating equivalence of cyclosporine ophthalmic emulsion PSDs that were manufactured under different conditions. Our results show that proposed approach can effectively pass an equivalent product (e.g., reference product against itself) and reject an inequivalent product (e.g., reference product against negative control), thus suggesting its usefulness in supporting bioequivalence determination of a test product to the reference product which both possess multimodal PSDs.

  4. 76 FR 34083 - Agency Information Collection Activities; Proposed Collection; Comment Request; Data To Support...

    Science.gov (United States)

    2011-06-10

    ... communication campaigns. Such knowledge will provide the needed target audience understanding to design... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0401... Communications Usability Testing, as Used by the Food and Drug Administration AGENCY: Food and Drug...

  5. 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.

  6. Final focus test beam alignment: A draft proposal

    International Nuclear Information System (INIS)

    Fischer, G.E.; Ruland, R.E.

    1989-03-01

    The Final Focus Test Beam is a transport line designed to transmit 50 GeV electron beams of SLC emittance (3 x 10 -10 radian-meters) straight through the central arm of the Beam Switchyard (BSY C line) with a final focus point out in the Research Yard but relatively near the end of the switchyard tunnel. The hardware, methods and procedures outlined in this proposal are dedicated to measuring the placement of mechanical objects with respect to certain defined geometric axes. We wish to emphasize that the very difficult problems of locating the effective magnetic axes of focusing elements, the effective electrical center of beam position monitors and even the effective axis of the incident beam relative to mechanical reference surfaces is outside the scope of this work. Further, this proposal is restricted to the act of measurement and does not consider the vital task of on-line mechanical repositioning of elements that will, in likelihood, be called upon during operation of the system. 16 refs., 16 figs., 4 tabs

  7. Does the FDA have regulatory authority over adult autologous stem cell therapies? 21 CFR 1271 and the emperor's new clothes

    Directory of Open Access Journals (Sweden)

    Freeman Michael

    2012-03-01

    Full Text Available Abstract FDA has recently asserted that many autologous cell therapies once considered the practice of medicine are in fact drugs. These changes began with the creation of new sections of 21 CFR 1271 and a subsequent one word change where the FDA, without public commentary, altered a single word in its regulatory language regarding cell and tissue based therapies that asserted the authority to classify autologous tissue as drugs. The bright line between medical care and drug production can be delineated in many ways, but a simple metric that defines the dichotomy is the consent status of the patient. In healthcare, a patient can either be consented individually for a medical procedure or exposed to an unconsented risk where regulatory assurances are already in place. These new FDA policies apply rules meant to keep drugs safe in a drug factory (unconsented mass production risks to individually consented surgical procedures. We argue that there is little societal benefit to these changes and that they are already stifling medical innovation.

  8. 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.

  9. 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.

  10. 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...

  11. Which factors predict proposal and uptake of psychological counselling after BRCA1/2 test result disclosure?

    Science.gov (United States)

    Maheu, Christine; Bouhnik, Anne-Deborah; Nogues, Catherine; Mouret-Fourme, Emmanuelle; Stoppa-Lyonnet, Dominique; Lasset, Christine; Berthet, Pascaline; Fricker, Jean-Pierre; Caron, Olivier; Luporsi, Elizabeth; Gladieff, Laurence; Julian-Reynier, Claire

    2014-04-01

    The aim of this study is to prospectively determine the factors contributing to whether unaffected women from BRCA1/2 families reported that clinicians proposed psychological consultations and that they had attended these consultations during the genetic testing process. A prospective study was performed on a national cohort, using self-administered questionnaires to determine the rates of proposal and use of psychological services at the time of BRCA1/2 test result disclosure (N = 533) and during the first year after disclosure (N = 478) among unaffected French women from BRCA1/2 families who had undergone genetic testing for BRCA1/2. Multivariate adjustment was carried out using logistic regression models fitted using generalized estimation equations, with the genetic testing centre as the clustering variable. At the time of BRCA1/2 test result disclosure, a psychological consultation was proposed by cancer geneticists to 72% and 32% of the carriers (N = 232) and noncarriers (N = 301), respectively (p disclosure, 21% of the carriers had consulted a psychologist, versus 9% of the noncarriers (p distress they experienced about their genetic test results (proposal AOR: 1.02; 95% CI 1.01-1.03; uptake AOR: 1.04; 95% CI 1.02-1.06) CONCLUSIONS: Determinants of the proposal/uptake of psychological consultations in the BRCA1/2 testing process highlight the need for inventive strategies to reach the different types of women's profiles. Copyright © 2013 John Wiley & Sons, Ltd.

  12. 2016 in review: FDA approvals of new molecular entities.

    Science.gov (United States)

    Griesenauer, Rebekah H; Kinch, Michael S

    2017-11-01

    An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Proposed optical test of Bell's inequalities not resting upon the fair sampling assumption

    International Nuclear Information System (INIS)

    Santos, Emilio

    2004-01-01

    Arguments are given against the fair sampling assumption, used to claim an empirical disproof of local realism. New tests are proposed, able to discriminate between quantum mechanics and a restricted, but appealing, family of local hidden-variables models. Such tests require detectors with efficiencies just above 20%

  14. 77 FR 19670 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food Contact...

    Science.gov (United States)

    2012-04-02

    ... Nutrition, Food and Drug Administration, 5100 Paint Branch Pkwy (HFS-275), College Park, MD 20740, 240-402... Nutrition using Form FDA 3480 whether it is submitted in electronic or paper format. FDA recently made minor... food contact articles. These notifications require the submission of Form FDA 3479 (``Notification for...

  15. 75 FR 43989 - Agency Information Collection Activities; Proposed Collection; Comment Request; Sample Collection...

    Science.gov (United States)

    2010-07-27

    ... use. To conduct the study, FDA would seek the voluntary participation of veterinarians in the private sector. FDA would contact veterinarians who have reported adverse events with SLENTROL to FDA using a... treated dog (breed, age, gender and neuter status, type of food), and information about past SLENTROL use...

  16. 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.

  17. 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.

  18. Novel 6FDA-based polyimides derived from sterically hindered Tröger's base diamines: Synthesis and gas permeation properties

    KAUST Repository

    Ghanem, Bader; Alaslai, Nasser Y.; Miao, Xiaohe; Pinnau, Ingo

    2016-01-01

    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.

  19. 75 FR 34745 - Agency Information Collection Activities; Proposed Collection; Comment Request; Survey on...

    Science.gov (United States)

    2010-06-18

    ... Communication Research at the University of Maryland. JIFSAN was established in 1996 and is a public and private partnership between FDA and the University of Maryland. The Center for Risk Communication Research will design... FDA to design more effective consumer food recall messages during and after a recall. FDA conducts...

  20. 76 FR 52333 - Agency Information Collection Activities; Proposed Collection; Comment Request; Tobacco Product...

    Science.gov (United States)

    2011-08-22

    ... chapter granting FDA important new authority to regulate the manufacture, marketing, and distribution of... part of its enforcement strategy, FDA created a Tobacco Call Center (with a toll-free number: 1-877-CTP.... Since a similar type of reporting went into effect for the cigarette flavor ban, FDA has received...

  1. A proposal on evaluation method of neutron absorption performance to substitute conventional neutron attenuation test

    International Nuclear Information System (INIS)

    Kim, Je Hyun; Shim, Chang Ho; Kim, Sung Hyun; Choe, Jung Hun; Cho, In Hak; Park, Hwan Seo; Park, Hyun Seo; Kim, Jung Ho; Kim, Yoon Ho

    2016-01-01

    For a verification of newly-developed neutron absorbers, one of guidelines on the qualification and acceptance of neutron absorbers is the neutron attenuation test. However, this approach can cause a problem for the qualifications that it cannot distinguish how the neutron attenuates from materials. In this study, an estimation method of neutron absorption performances for materials is proposed to detect both direct penetration and back-scattering neutrons. For the verification of the proposed method, MCNP simulations with the experimental system designed in this study were pursued using the polyethylene, iron, normal glass and the vitrified form. The results show that it can easily test neutron absorption ability using single absorber model. Also, from simulation results of single absorber and double absorbers model, it is verified that the proposed method can evaluate not only the direct thermal neutrons passing through materials, but also the scattered neutrons reflected to the materials. Therefore, the neutron absorption performances can be accurately estimated using the proposed method comparing with the conventional neutron attenuation test. It is expected that the proposed method can contribute to increase the reliability of the performance of neutron absorbers

  2. A proposal on evaluation method of neutron absorption performance to substitute conventional neutron attenuation test

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Je Hyun; Shim, Chang Ho [Dept. of Nuclear Engineering, Hanyang University, Seoul (Korea, Republic of); Kim, Sung Hyun [Nuclear Fuel Cycle Waste Treatment Research Division, Research Reactor Institute, Kyoto University, Osaka (Japan); Choe, Jung Hun; Cho, In Hak; Park, Hwan Seo [Ionizing Radiation Center, Nuclear Fuel Cycle Waste Treatment Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Park, Hyun Seo; Kim, Jung Ho; Kim, Yoon Ho [Ionizing Radiation Center, Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2016-12-15

    For a verification of newly-developed neutron absorbers, one of guidelines on the qualification and acceptance of neutron absorbers is the neutron attenuation test. However, this approach can cause a problem for the qualifications that it cannot distinguish how the neutron attenuates from materials. In this study, an estimation method of neutron absorption performances for materials is proposed to detect both direct penetration and back-scattering neutrons. For the verification of the proposed method, MCNP simulations with the experimental system designed in this study were pursued using the polyethylene, iron, normal glass and the vitrified form. The results show that it can easily test neutron absorption ability using single absorber model. Also, from simulation results of single absorber and double absorbers model, it is verified that the proposed method can evaluate not only the direct thermal neutrons passing through materials, but also the scattered neutrons reflected to the materials. Therefore, the neutron absorption performances can be accurately estimated using the proposed method comparing with the conventional neutron attenuation test. It is expected that the proposed method can contribute to increase the reliability of the performance of neutron absorbers.

  3. 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...

  4. Information Regarding the OraQuick In-Home HIV Test

    Science.gov (United States)

    ... detect HIV infection. Therefore, FDA cannot give the public any assurance that the results obtained using an unapproved test system are accurate. back to top More Information How can I obtain additional information about the ...

  5. 75 FR 11545 - Agency Information Collection Activities; Proposed Collection; Comment Request; Human Cells...

    Science.gov (United States)

    2010-03-11

    ... and report to FDA adverse reactions (defined in Sec. 1271.3(y)) using Form FDA-3500A (Sec. 1271.350(a.... 1271.290(f). FDA estimates 38 HCT[sol]P establishments submitted 76 adverse reaction reports involving... conventional tissue donors, eye tissue donors, peripheral and cord blood stem cell donors, and reproductive...

  6. A comment on a proposed ''crucial experiment'' to test Einstein's special theory of relativity

    International Nuclear Information System (INIS)

    Rodrigues Jr, W.A.; Buonamano, V.

    1976-01-01

    A proposed ''crucial experiment'' to test Einstein's special theory of relativity is analysed and it is shown that it falls into the set of unsatisfactory proposals that attempt to make an experimental distinction between Einstein's special theory of relativity and a ''Lorentzian type'' special theory of relativity

  7. 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

  8. 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

  9. NCI-FDA Interagency Oncology Task Force Workshop Provides Guidance for Analytical Validation of Protein-based Multiplex Assays | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to

  10. 76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

    Science.gov (United States)

    2011-07-14

    ...., Bldg. 51, rm. 2201, Silver Spring, MD 20993- 0002, or Office of Communication, Outreach and Development... help make critical treatment decisions. FDA oversight of companion diagnostics will protect patients... current thinking on companion diagnostic devices. It does not create or confer any rights for or on any...

  11. 76 FR 13643 - FDA Food Safety Modernization Act: Title III-A New Paradigm for Importers; Public Meeting

    Science.gov (United States)

    2011-03-14

    ... Act: Title III--A New Paradigm for Importers; Public Meeting AGENCY: Food and Drug Administration, HHS... announcing a public meeting entitled ``FDA Food Safety Modernization Act: Title III--A New Paradigm for... provided. Request special accommodations due By March 22, 2011.... Patricia M. Kuntze, 301- to disability...

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. A United States regulator's perspective on the ongoing chlorofluorocarbon transition.

    Science.gov (United States)

    Meyer, R J

    1999-12-01

    The Food and Drug Administration (FDA) put in place a general ban on the use of chlorofluorocarbons for the products it regulates (medical devices, drugs, and foods) in 1978, exempting those products where chlorofluorocarbon use was determined to be essential for the public health. In the intervening years, as the international commitment to a full transition away from all chlorofluorocarbon use took shape under the Montreal Protocol, the FDA has worked with industry to facilitate the development and testing of alternative technologies and products for inhalation drug products. As these alternative products begin to move from testing through the approval process and into marketing, the FDA is working collaboratively with the Environmental Protection Agency, other governmental agencies, and nongovernmental stakeholders to develop a transition policy for the United States. The transition policy for metered dose inhalers must be one that achieves the dual aims of first protecting the patients who rely on these vital medical products, while also achieving the public health need of protecting the ozone layer. As a part of developing such a transition strategy, the FDA published an advance notice of proposed rulemaking (ANPRM) in March 1997. The ANPRM proposed mechanisms by which the FDA could determine when chlorofluorocarbon use in a drug product could no longer be considered essential. The ANPRM resulted in a large amount of valuable public debate and input. The FDA is now working to incorporate the knowledge gained from these public comments as it continues the rule-making process.

  17. Proposed particle-beam characterizations for the APS undulator test line

    Energy Technology Data Exchange (ETDEWEB)

    Lumpkin, A.H.; Borland, M.; Milton, S.

    1993-09-01

    A research and development effort is underway at the Advanced Photon Source (APS) to use an rf gun as a low-emittance electron source for injection into the 100- to 650-MeV linac subsystem and subsequently to an undulator test area. This configuration would combine the acceleration capability of the 200-MeV S-band electron linac and the in-line 450-MeV positron linac that normally provide positrons to the positron accumulator ring (PAR). A transport line that bypasses the PAR will bring the electrons to the undulator test area. Characterization techniques will be discussed for the electron beam with a normalized, rms emittance of <10 {pi} mm mrad (1{sigma}) at micropulse charges of up to 350 pC and micropulse durations of {approximately}5 ps (FWHM). Tests proposed include measurement of particle beam transport effects (at one-tenth the storage ring beam rigidity) caused by small undulator field errors as well as operations intended to produce coherent, short wavelength radiation (<200 nm).

  18. 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

  19. Rapid toxicity assessment using an in vivo enzyme test for Brachionus plicatilis (Rotifera).

    Science.gov (United States)

    Moffat, B D; Snell, T W

    1995-02-01

    A 1-hr in vivo enzyme inhibition assay based on esterase activity has good potential for marine toxicity assessment. A test was developed for the rotifer Brachionus plicatilis based on the nonfluorescent substrate fluorescein diacetate (FDA), which is metabolized by esterases to a fluorescent product. Enzyme inhibition, as determined by reduced fluorescence, can be scored visually or quantified using a fluorometer. Quantification of fluorescence permits the calculation of NOEC, LOEC, chronic value, and IC20. The 1-hr esterase inhibition test has sensitivity comparable to that of 24-hr rotifer acute tests for several compounds. The toxicity of six compounds was examined using the quantified assay. The resulting IC20s were within a factor of 3 of the 24-hour LC50s. IC20 values ranged from 0.017 mg/l for tributyltin to 3.1 mg/l for zinc, with an average coefficient of variation of 17.8%. Electrophoretic analysis of rotifer homogenates suggested that a single C esterase (acetylesterase) was responsible for FDA metabolism in B. plicatilis. Several other aquatic species are capable of metabolizing FDA, including Brachionus calyciflorus, Mysidopsis bahia, Menidia beryllina, Pimephales promelas, Ceriodaphnia dubia, Daphnia pulex, Artemia salina, and Ophryotrocha sp. The esterase inhibition test is an attractive tool for assessing aquatic toxicity because of its speed, simplicity, sensitivity, and applicability to a broad range of aquatic species.

  20. The bootstrap and Bayesian bootstrap method in assessing bioequivalence

    International Nuclear Information System (INIS)

    Wan Jianping; Zhang Kongsheng; Chen Hui

    2009-01-01

    Parametric method for assessing individual bioequivalence (IBE) may concentrate on the hypothesis that the PK responses are normal. Nonparametric method for evaluating IBE would be bootstrap method. In 2001, the United States Food and Drug Administration (FDA) proposed a draft guidance. The purpose of this article is to evaluate the IBE between test drug and reference drug by bootstrap and Bayesian bootstrap method. We study the power of bootstrap test procedures and the parametric test procedures in FDA (2001). We find that the Bayesian bootstrap method is the most excellent.

  1. 78 FR 55724 - Agency Information Collection Activities; Proposed Collection; Comment Request; Recommended...

    Science.gov (United States)

    2013-09-11

    ... submit a license application for FDA review and approval prior to marketing a biological product for introduction into interstate commerce. In the Federal Register of November 30, 2004 (69 FR 69606), FDA...

  2. Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

    Science.gov (United States)

    Miller, Jennifer E; Korn, David; Ross, Joseph S

    2015-01-01

    Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve

  3. In vitro vaccine potency testing: a proposal for reducing animal use for requalification testing.

    Science.gov (United States)

    Brown, K; Stokes, W

    2012-01-01

    This paper proposes a program under which the use of animals for requalification of in vitro potency tests could be eliminated. Standard References (USDA/CVB nomenclature) would be developed, characterized, stored and monitored by selected reference laboratories worldwide. These laboratories would employ scientists skilled in protein and glycoprotein chemistry and equipped with state-of-the-art instruments for required analyses. After Standard References are established, the reference laboratories would provide them to the animal health industry as "gold standards". Companies would then establish and validate a correlation between the Standard Reference and the company Master Reference (USDA/CVB nomenclature) using an internal in vitro assay. After this correlation is established, the company could use the Standard References for qualifying, monitoring and requalifying company Master References without the use of animals. Such a program would eliminate the need for animals for requalification of Master References and the need for each company to develop and validate a battery of Master Reference Monitoring assays. It would also provide advantages in terms of reduced costs and reduced time for requalification testing. As such it would provide a strong incentive for companies to develop and use in vitro assays for potency testing.

  4. Proposing and testing SOA governance process: A case study approach

    DEFF Research Database (Denmark)

    Koumaditis, Konstantinos; Themistocleous, Marinos

    2015-01-01

    Longstanding Healthcare Information Systems (HIS) integration challenges drove healthcare organisations to invest in new paradigms like Service Oriented Architecture (SOA). Yet, SOA holds challenges of its own, with SOA Governance surfacing on the top. This research depicts the development......, grounded in the normative literature and further developed to include healthcare aspects. The proposition is tested in a large Greek hospital utilising qualitative methods and the findings presented herein. This proposal aims to pinpoint attributes and guidelines for SOA Governance Process, required...

  5. Test-retest reliability of the proposed DSM-5 eating disorder diagnostic criteria

    Science.gov (United States)

    Sysko, Robyn; Roberto, Christina A.; Barnes, Rachel D.; Grilo, Carlos M.; Attia, Evelyn; Walsh, B. Timothy

    2012-01-01

    The proposed DSM-5 classification scheme for eating disorders includes both major and minor changes to the existing DSM-IV diagnostic criteria. It is not known what effect these modifications will have on the ability to make reliable diagnoses. Two studies were conducted to evaluate the short-term test-retest reliability of the proposed DSM-5 eating disorder diagnoses: anorexia nervosa, bulimia nervosa, binge eating disorder, and feeding and eating conditions not elsewhere classified. Participants completed two independent telephone interviews with research assessors (n=70 Study 1; n=55 Study 2). Fair to substantial agreements (κ= 0.80 and 0.54) were observed across eating disorder diagnoses in Study 1 and Study 2, respectively. Acceptable rates of agreement were identified for the individual eating disorder diagnoses, including DSM-5 anorexia nervosa (κ’s of 0.81 to 0.97), bulimia nervosa (κ=0.84), binge eating disorder (κ’s of 0.75 and 0.61), and feeding and eating disorders not elsewhere classified (κ’s of 0.70 and 0.46). Further, improved short-term test-retest reliability was noted when using the DSM-5, in comparison to DSM-IV, criteria for binge eating disorder. Thus, these studies found that trained interviewers can reliably diagnose eating disorders using the proposed DSM-5 criteria; however, additional data from general practice settings and community samples are needed. PMID:22401974

  6. 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.

  7. The FDA Unapproved Drugs Initiative: An Observational Study of the Consequences for Drug Prices and Shortages in the United States.

    Science.gov (United States)

    Gupta, Ravi; Dhruva, Sanket S; Fox, Erin R; Ross, Joseph S

    2017-10-01

    Hundreds of drug products are currently marketed in the United States without approval from the FDA. The 2006 Unapproved Drugs Initiative (UDI) requires manufacturers to remove these drug products from the market or obtain FDA approval by demonstrating evidence of safety and efficacy. Once the FDA acts against an unapproved drug, fewer manufacturers remain in the market, potentially enabling drug price increases and greater susceptibility to drug shortages. There is a need for systematic study of the UDI's effect on prices and shortages of all targeted drugs. To examine the clinical evidence for approval and association with prices and shortages of previously unapproved prescription drugs after being addressed by the UDI. Previously unapproved prescription drugs that faced UDI regulatory action or with at least 1 product that received FDA approval through manufacturers' voluntary compliance with the UDI between 2006 and 2015 were identified. The clinical evidence was categorized as either newly conducted clinical trials or use of previously published literature and/or bioequivalence studies to demonstrate safety and efficacy. We determined the change in average wholesale price, presence of shortage, and duration of shortage for each drug during the 2 years before and after UDI regulatory action or approval through voluntary compliance. Between 2006 and 2015, 34 previously unapproved prescription drugs were addressed by the UDI. Nearly 90% of those with a drug product that received FDA approval were supported by literature reviews or bioequivalence studies, not new clinical trial evidence. Among the 26 drugs with available pricing data, average wholesale price during the 2 years before and after voluntary approval or UDI action increased by a median of 37% (interquartile range [IQR] = 23%-204%; P Innovation; from the Blue Cross Blue Shield Association to better understand medical technology evidence generation; from the Centers for Medicare & Medicaid Services to

  8. Proposed Industry Best Practices in Development and Marketing of Medical Foods for the Management of Chronic Conditions and Diseases while Awaiting Regulation.

    Science.gov (United States)

    Burnett, Bruce; Levy, Robert M

    Ideal therapeutics have low toxicity and can effectively manage condition(s) or disease(s). The Food & Drug Administration (FDA) marketing category of therapeutics called “medical foods” (MFs) meets such a definition. Medical foods have existed in Federal law since passage the Orphan Drug Act in 1988, which created a category of nutritional therapeutics separate from drugs. Unfortunately, MFs are not widely understood by the medical community or utilized in all patients who need them due to lack of a FDA-approval process, unclear and contradictory guidance especially with regard for need for an investigational new drug (IND) application, and no clear regulations regarding their development and marketing. The goals of this article are to propose “Best Practices” to guide the medical food industry in the development and marketing of products as well as to serve as a starting point for suggestions regarding further FDA regulation so that therapeutics which are shown to be generally recognized as safe (GRAS), provide food ingredients to meet a distinctive nutritional requirement for a specific condition/disease and are proven effective for the management for that condition/disease can be used to benefit patients who need them.

  9. Proposal of concentration limits for determining the hazard property HP 14 for waste using ecotoxicological tests.

    Science.gov (United States)

    Hennebert, Pierre

    2018-04-01

    Different ecotoxicological test batteries and concentration limits have been proposed to assess the hazard property (HP) HP 14 'Ecotoxic' for waste in the European Union and its member states. In test batteries, if the concentration of waste in the culture/dilution medium producing 50% of inhibitory biological effect in one or more test(s) is below the concentration limit of the test, the waste is classified as hazardous. A summarized review of the test batteries proposed since 1998 is presented. The last proposed test battery uses seven aquatic and terrestrial species with standardized methods, but with options and uniform concentration limits of 10% of waste eluate or solid waste in the culture/dilution medium. No attempt was made to match this hazard assessment with the classification made in the European List of Waste (LoW). The aim of this paper is to propose for the same test battery (reduced to 6 tests without options) concentration limits that match with the European List of Waste. This list was taken as reference (despite the fact that waste can be hazardous for other properties than the most frequent HP 14, and its partly political nature for some opinions). The concentration limits (CLs) for tests are the concentrations producing the highest ecotoxicological effects for each test observed in a non-hazardous waste set. Data from Germany, France and Belgium (from in total 5 different sources from 2009 to 2016) with the above-mentioned test battery (without options) were gathered for 81 samples, being the largest set ever published. In total, ten non-hazardous (NH) waste samples (as defined by the LoW and for most of them checked by chemical composition) were used to establish CLs. These CLs were then applied to 13 hazardous (H) waste by the LoW, and all were classified as hazardous. The matching of the resulting classification with the LoW is convincing. For the 58 'mirror entries' in the LoW (hazardous or not depending of the presence of hazardous

  10. 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.

  11. 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.

  12. Proposal for a Universal Test Mirror for Characterization of Slope Measuring Instruments

    International Nuclear Information System (INIS)

    Yashchuk, Valeriy V.; McKinney, Wayne R.; Warwick, Tony; Noll, Tino; Siewert, Frank; Zeschke, Thomas; Geckeler, Ralf D.

    2007-01-01

    The development of third generation light sources like the Advanced Light Source (ALS) or BESSY II brought to a focus the need for high performance synchrotron optics with unprecedented tolerances for slope error and micro roughness. Proposed beam lines at Free Electron Lasers (FEL) require optical elements up to a length of one meter, characterized by a residual slope error in the range of 0.1mu rad (rms),and rms values of 0.1 nm for micro roughness. These optical elements must be inspected by highly accurate measuring instruments, providing a measurement uncertainty lower than the specified accuracy of the surface under test. It is essential that metrology devices in use at synchrotron laboratories be precisely characterized and calibrated to achieve this target. In this paper we discuss a proposal for a Universal Test Mirror (UTM) as a realization of a high performance calibration instrument. The instrument would provide an ideal calibration surface to replicate a redundant surface under test of redundant figure. The application of a sophisticated calibration instrument will allow the elimination of the majority of the systematic error from the error budget of an individual measurement of a particular optical element. We present the limitations of existing methods, initial UTM design considerations, possible calibration algorithms, and an estimation of the expected accuracy

  13. Two-Dimensional Model Test Study of New Western Breakwater Proposal for Port of Hanstholm

    OpenAIRE

    Eldrup, Mads Røge; Andersen, Thomas Lykke

    2016-01-01

    The present report presents results from a two-dimensional model test study carried out at Aalborg University in December 2016 with the proposed trunk section for the new western breakwater in Port of Hanstholm. The objectives of the model tests were to study the stability of the armour layer, toe erosion, overtopping and transmission. The scale used for the model tests was 1:61.5. Unless otherwise specified all values given in this report are prototype values converted from the model to prot...

  14. 75 FR 39954 - Oversight of Laboratory Developed Tests; Public Meeting; Change of Meeting Location

    Science.gov (United States)

    2010-07-13

    ...] Oversight of Laboratory Developed Tests; Public Meeting; Change of Meeting Location AGENCY: Food and Drug... location for the upcoming public meeting entitled ``Oversight of Laboratory Developed Tests.'' A new... the public meeting, FDA is announcing in this notice a new location for the public meeting. II. New...

  15. 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...

  16. Proposed experimental test of the theory of hole superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Hirsch, J.E., E-mail: jhirsch@ucsd.edu

    2016-06-15

    Highlights: • The conventional theory of superconductivity predicts no charge flow when the normal-superconductor phase boundary moves. • The theory of hole superconductivity predicts flow and counterflow of charge. • An experiment to measure a voltage is proposed. • No voltage will be measured if the conventional theory is correct. • A voltage will be measured if the theory of hole superconductivity is correct. - Abstract: The theory of hole superconductivity predicts that in the reversible transition between normal and superconducting phases in the presence of a magnetic field there is charge flow in direction perpendicular to the normal-superconductor phase boundary. In contrast, the conventional BCS-London theory of superconductivity predicts no such charge flow. Here we discuss an experiment to test these predictions.

  17. 77 FR 48988 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental...

    Science.gov (United States)

    2012-08-15

    ... Division of Dockets Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061... beverages). FDA is interested in studying whether fortification of these foods could cause consumers to... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0871...

  18. 76 FR 16350 - Medical Devices; Ovarian Adnexal Mass Assessment Score Test System; Labeling; Black Box Restrictions

    Science.gov (United States)

    2011-03-23

    ... inflation) in any one year.'' The current threshold after adjustment for inflation is $135 million, using the most current (2009) Implicit Price Deflator for the Gross Domestic Product. FDA does not expect... proposes to amend 21 CFR part 866 as follows. PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES 1. The...

  19. Proposed quality control guidelines for National Committee for Clinical Laboratory Standards Susceptibility Tests using the veterinary antimicrobial agent tiamulin.

    Science.gov (United States)

    Pfaller, M A; Jones, R N; Walter, D H

    2001-01-01

    Quality control guidelines for standardized antimicrobial susceptibility test methods are critical for the continuing accuracy of these clinical tests. In this report, quality control limits were proposed for the veterinary antimicrobial agent tiamulin with minimum inhibitory concentration (MIC) ranges of three or four log(2) dilution steps in two different medium formulations. Disk diffusion zone diameter ranges were proposed for tiamulin tested against Actinobacillus pleuropneumoniae ATCC 27090 (12-18 mm) and Staphylococcus aureus ATCC 25923 (25-32 mm). The data from eight participating laboratories produced 100% of results within proposed MIC limits (8-32 microg/mL), and 95.8-97.0% of zones were found within suggested zone diameter QC guidelines. These proposed QC ranges should be validated by in-use results from veterinary clinical laboratories.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Experimental testing on free vibration behaviour for silicone rubbers proposed within lumbar disc prosthesis

    Energy Technology Data Exchange (ETDEWEB)

    Rotaru, Iuliana, E-mail: rotaruiuliana2000@gmail.com [“Gheorghe Asachi” Technical University of Iasi, Faculty of Mechanical Engineering, Department of Mechanical Engineering, Mechatronics and Robotics, 61-63 Bd. Dimitrie Mangeron, 700050 Iasi (Romania); “Gr. T. Popa” University of Medicine and Pharmacy of Iasi, Faculty of Medical Bioengineering, Department of Biomedical Sciences, 9-13 M. Kogalniceanu Street, 700454 Iasi (Romania); Bujoreanu, Carmen [“Gheorghe Asachi” Technical University of Iasi, Faculty of Mechanical Engineering, Department of Mechanical Engineering, Mechatronics and Robotics, 61-63 Bd. Dimitrie Mangeron, 700050 Iasi (Romania); Bele, Adrian; Cazacu, Maria [“Petru Poni” Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi (Romania); Olaru, Dumitru [“Gheorghe Asachi” Technical University of Iasi, Faculty of Mechanical Engineering, Department of Mechanical Engineering, Mechatronics and Robotics, 61-63 Bd. Dimitrie Mangeron, 700050 Iasi (Romania)

    2014-09-01

    This research was focused on the damping capacity study of two types of silicone rubbers proposed as layers within total lumbar disc prostheses of ball-and-socket model. In order to investigate the damping capacity, the two silicone rubber types mainly differing by the molecular mass of polymeric matrix and the filler content, as was emphasized by scanning electron microscopy and differential scanning calorimetry, were subjected to free vibration testing. Using an adapted experimental installation, three kinds of damping testing were realised: tests without samples and tests with three samples of each type of silicone rubber (69 ShA and 99 ShA). The free vibration tests were performed at a frequency of about 6 Hz using a weight of 11.8 kg. The relative damping coefficient was determined by measuring of two successive amplitudes on the vibrogram and calculating of the logarithmic decrement. The test results with silicone rubber samples showed a relative damping coefficient of 0.058 and respectively 0.077, whilst test results without samples showed a relative damping coefficient of 0.042. These silicone rubbers were found to have acceptable damping properties to be used as layers placed inside the prosthetic components. - Highlights: • Two types of silicone rubber were proposed within the total lumbar disc prostheses. • The filler content of elastomers was highlighted by microscopy investigation. • Damping capacity of the two elastomers was evaluated using free vibration analysis. • The logarithmic decrement and the relative damping coefficient were determined. • The silicone rubbers prepared in our work showed acceptable damping properties.

  5. Experimental testing on free vibration behaviour for silicone rubbers proposed within lumbar disc prosthesis

    International Nuclear Information System (INIS)

    Rotaru, Iuliana; Bujoreanu, Carmen; Bele, Adrian; Cazacu, Maria; Olaru, Dumitru

    2014-01-01

    This research was focused on the damping capacity study of two types of silicone rubbers proposed as layers within total lumbar disc prostheses of ball-and-socket model. In order to investigate the damping capacity, the two silicone rubber types mainly differing by the molecular mass of polymeric matrix and the filler content, as was emphasized by scanning electron microscopy and differential scanning calorimetry, were subjected to free vibration testing. Using an adapted experimental installation, three kinds of damping testing were realised: tests without samples and tests with three samples of each type of silicone rubber (69 ShA and 99 ShA). The free vibration tests were performed at a frequency of about 6 Hz using a weight of 11.8 kg. The relative damping coefficient was determined by measuring of two successive amplitudes on the vibrogram and calculating of the logarithmic decrement. The test results with silicone rubber samples showed a relative damping coefficient of 0.058 and respectively 0.077, whilst test results without samples showed a relative damping coefficient of 0.042. These silicone rubbers were found to have acceptable damping properties to be used as layers placed inside the prosthetic components. - Highlights: • Two types of silicone rubber were proposed within the total lumbar disc prostheses. • The filler content of elastomers was highlighted by microscopy investigation. • Damping capacity of the two elastomers was evaluated using free vibration analysis. • The logarithmic decrement and the relative damping coefficient were determined. • The silicone rubbers prepared in our work showed acceptable damping properties

  6. 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.

  7. FDA-Approved Natural Polymers for Fast Dissolving Tablets

    Directory of Open Access Journals (Sweden)

    Md Tausif Alam

    2014-01-01

    Full Text Available Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing, in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets.

  8. 77 FR 49819 - Agency Information Collection Activities; Proposed Collection; Comment Request; Pretesting of...

    Science.gov (United States)

    2012-08-17

    ... assess the likely effectiveness of tobacco communications with specific target audiences. The information... needed about target audiences. FDA must first understand critical influences on people's decisionmaking... intended audiences. Pretesting messages with a sample of the target audience will allow FDA to refine...

  9. 75 FR 9225 - Agency Information Collection Activities; Proposed Collection; Comment Request; Pretesting of...

    Science.gov (United States)

    2010-03-01

    ... assess the likely effectiveness of tobacco communications with specific target audiences. The information... needed about target audiences. FDA must first understand critical influences on people's decisionmaking... intended audiences. Pretesting messages with a sample of the target audience will allow FDA to refine...

  10. 78 FR 78974 - Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for...

    Science.gov (United States)

    2013-12-27

    ... chapter granting FDA authority to regulate the manufacture, marketing, and distribution of tobacco... related to substantial equivalence. In a Level 1 guidance document issued under the Good Guidances Practices regulation (21 CFR 10.115), FDA provides recommendations intended to assist persons submitting...

  11. 76 FR 20679 - Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for...

    Science.gov (United States)

    2011-04-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0157...: Fast Track Drug Development Programs: Designation, Development, and Application Review AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

  12. Two-Dimensional Model Test Study of New Western Breakwater Proposal for Port of Hanstholm

    DEFF Research Database (Denmark)

    Eldrup, Mads Røge; Andersen, Thomas Lykke

    The present report presents results from a two-dimensional model test study carried out at Aalborg University in December 2016 with the proposed trunk section for the new western breakwater in Port of Hanstholm. The objectives of the model tests were to study the stability of the armour layer, toe...... erosion, overtopping and transmission. The scale used for the model tests was 1:61.5. Unless otherwise specified all values given in this report are prototype values converted from the model to prototype according to the Froude model law....

  13. 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.

  14. Environmental assessment of proposed geothermal well testing in the Tigre Lagoon Oil Field, Vermilion Parish, Louisiana

    Energy Technology Data Exchange (ETDEWEB)

    1976-03-01

    An environmental assessment is made of the proposed testing of two geopressured, geothermal aquifers in central coastal Louisiana. On the basis of an analysis of the environmental setting, subsurface characteristics, and the proposed action, potential environmental impacts are determined and evaluated together with potential conflicts with federal, state, and local programs. (LBS )

  15. Proposed experimental test of Bell's inequality in nuclear beta decay

    International Nuclear Information System (INIS)

    Skalsey, M.

    1986-01-01

    A β decay experiment is proposed for testing Bell's inequality, related to hidden-variables alternatives to quantum mechanics. The experiment uses Mott scattering for spin polarization analysis of internal conversion electrons. Beta-decay electrons, in cascade with the conversion electrons, are longitudinally polarized due to parity violation in the weak interaction. So simply detecting the β electron direction effectively measures the spin. A two-particle spin-spin correlation can thus be investigated and related, within certain assumptions, to Bell's inequality. The example of 203 Hg decay is used for a calculation of expected results. Specific problems related to nuclear structure and experimental inconsistencies are also discussed

  16. 77 FR 12089 - Proposed Generic Communication; Regulatory Issue Summary 2012-XX: Developing Inservice Testing...

    Science.gov (United States)

    2012-02-28

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0048] Proposed Generic Communication; Regulatory Issue... CFR) Part 52, ``Licenses, Certifications, and Approvals for Nuclear Power Plants,'' to satisfy the... inservice testing programs during the initial 120-month program interval following nuclear power plant...

  17. Pilot-plant testing of materials proposed for use as NWCF feed and fuel nozzle caps

    International Nuclear Information System (INIS)

    Birrer, S.A.

    1980-12-01

    Results of a series of tests performed on materials proposed for use at New Waste Calcining Facility (NWCF) fuel and feed nozzle caps are described. Results show that Haynes Alloys 25 and 188 and Inconel Alloys 617, 625, and 690 have acceptable corrosion and erosion rates based upon the high-temperature oxidation, erosion, and corrosion tests conducted

  18. Teste de figuras para discriminação fonêmica: uma proposta Phoneme Discrimination Picture Test: a proposal

    Directory of Open Access Journals (Sweden)

    Beatriz dos Santos-Carvalho

    2008-01-01

    Full Text Available OBJETIVOS: Propor um teste que avaliasse a discriminação fonêmica por meio de pares mínimos, abrangendo todos os fonemas do Português Brasileiro e utilizando-os em palavras que possam ser facilmente representadas por figuras. Buscou-se que este teste contribua para o diagnóstico de alterações fonoaudiológicas e para a pesquisa científica. Procurou-se fazer um teste que fosse de fácil aplicação, podendo ser utilizado em qualquer local de trabalho dos fonoaudiólogos. MÉTODOS: Selecionou-se pares mínimos que opusessem fonemas em relação ao valor binário de cada traço distintivo e às combinações possíveis entre os traços de lugar ([labial], [coronal], [dorsal] bem como pelas oposições de estruturas silábicas. Criou-se figuras que representam as palavras dos pares. RESULTADOS: Elaborou-se o Teste de Figuras para Discriminação Fonêmica, que avalia a habilidade de discriminação fonêmica em crianças de quatro a oito anos. Este teste contém 40 apresentações, das quais 30 são pares mínimos e dez pares de palavras iguais. Nestas 30 apresentações, opôs-se os traços distintivos [+/- soante], [+/- aproximante], [+/- contínuo], [+/- voz], [coronal+/-ant], [labial] x [coronal], [dorsal] x [coronal] e [labial] x [dorsal]. Igualmente foram opostas as seguintes estruturas silábicas: V x CV, CV x CCV, CV x CVC. CONCLUSÃO: Conclui-se que os objetivos deste trabalho foram alcançados com êxito, pois o Teste de Figura para Discriminação Fonêmica contempla tudo a que se propôs. Acredita-se que o teste deva ser aplicado em um estudo piloto para averiguar se as palavras e as figuras estão adequadas para a faixa etária. Posteriormente, deve ser aplicado em diversas regiões do país para ser devidamente padronizado.PURPOSE: To propose a test to evaluate phonemic discrimination using minimum pairs, comprising all Brazilian Portuguese phonemes and using them in words which can be easily represented by pictures. The

  19. 78 FR 16676 - Agency Information Collection Activities; Proposed Collection; Comment Request; Draft Guidance...

    Science.gov (United States)

    2013-03-18

    ... the applicable hazards will need to be re-evaluated at multiple stages of the development process. In... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0194... Industry and FDA Staff; Total Product Life Cycle: Infusion Pump--Premarket Notification [510(k...

  20. 78 FR 28851 - Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for...

    Science.gov (United States)

    2013-05-16

    ...: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing an opportunity for public comment... information, and to allow 60 days for public comment in response to the notice. This notice solicits comments... Submission System to Submit Information in Electronic Format using the FDA Electronic Submissions Gateway...

  1. 78 FR 68454 - Agency Information Collection Activities; Proposed Collection; Comment Request; Patent Term...

    Science.gov (United States)

    2013-11-14

    ... review period revision. Where a patented product must receive FDA approval before marketing is permitted.... Petitioners may request reductions in the regulatory review time if FDA marketing approval was not pursued..., including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility...

  2. 75 FR 61493 - Agency Information Collection Activities; Proposed Collection; Comment Request; Patent Term...

    Science.gov (United States)

    2010-10-05

    ... review period revision. Where a patented product must receive FDA approval before marketing is permitted.... Petitioners may request reductions in the regulatory review time if FDA marketing approval was not pursued... information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality...

  3. Testing the Construct Validity of Proposed Criteria for "DSM-5" Autism Spectrum Disorder

    Science.gov (United States)

    Mandy, William P. L.; Charman, Tony; Skuse, David H.

    2012-01-01

    Objective: To use confirmatory factor analysis to test the construct validity of the proposed "DSM-5" symptom model of autism spectrum disorder (ASD), in comparison to alternative models, including that described in "DSM-IV-TR." Method: Participants were 708 verbal children and young persons (mean age, 9.5 years) with mild to severe autistic…

  4. Proposed new ultrasonic test bed

    International Nuclear Information System (INIS)

    Maxfield, B.W.

    1978-01-01

    Within the last four or five years, a great deal of progress has been made both here and in a number of other laboratories in developing techniques that will enable considerably more information to be obtained from the ultrasonic examination of an object. Some of these recent developments relate to information contained within the diffracted beam which does not return along the incident path. An ultrasonic examination based upon an evaluation of diffracted energy must use at least two transducers, one for transmission and the other for reception. Current indications are that even more reliable test results will be achieved using a receiving transducer that can scan a significant portion of the diffracted field including that portion which is back-reflected. In general, this scan can be interpreted most accurately if it follows a path related to the surface shape. If more than one region within the object is to be interrogated, then the transmitting transducer must also be scanned, again along a path related to the surface shape. The large quantity of information obtained as the result of such an examination must be subjected to sophisticated computer analysis in order to be displayed in a meaningful and intelligible manner. Although one motivation for building such an instrument is to explore new ultrasonic test procedures that are evolving from current laboratory research, this is neither the sole motivation nor the only use for this instrument. Such a mechanical and electronic device would permit conventional ultrasonic tests to be performed on parts of complex geometry without the expensive and time-consuming special fixturing that is currently required. May possible test geometries could be explored in practice prior to the construction of a specialized test apparatus. Hence, it would be necessary to design much, if any, flexibility into the special test apparatus

  5. 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

  6. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

    Science.gov (United States)

    Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

    2018-03-21

    The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95

  7. QUADrATiC: scalable gene expression connectivity mapping for repurposing FDA-approved therapeutics.

    Science.gov (United States)

    O'Reilly, Paul G; Wen, Qing; Bankhead, Peter; Dunne, Philip D; McArt, Darragh G; McPherson, Suzanne; Hamilton, Peter W; Mills, Ken I; Zhang, Shu-Dong

    2016-05-04

    Gene expression connectivity mapping has proven to be a powerful and flexible tool for research. Its application has been shown in a broad range of research topics, most commonly as a means of identifying potential small molecule compounds, which may be further investigated as candidates for repurposing to treat diseases. The public release of voluminous data from the Library of Integrated Cellular Signatures (LINCS) programme further enhanced the utilities and potentials of gene expression connectivity mapping in biomedicine. We describe QUADrATiC ( http://go.qub.ac.uk/QUADrATiC ), a user-friendly tool for the exploration of gene expression connectivity on the subset of the LINCS data set corresponding to FDA-approved small molecule compounds. It enables the identification of compounds for repurposing therapeutic potentials. The software is designed to cope with the increased volume of data over existing tools, by taking advantage of multicore computing architectures to provide a scalable solution, which may be installed and operated on a range of computers, from laptops to servers. This scalability is provided by the use of the modern concurrent programming paradigm provided by the Akka framework. The QUADrATiC Graphical User Interface (GUI) has been developed using advanced Javascript frameworks, providing novel visualization capabilities for further analysis of connections. There is also a web services interface, allowing integration with other programs or scripts. QUADrATiC has been shown to provide an improvement over existing connectivity map software, in terms of scope (based on the LINCS data set), applicability (using FDA-approved compounds), usability and speed. It offers potential to biological researchers to analyze transcriptional data and generate potential therapeutics for focussed study in the lab. QUADrATiC represents a step change in the process of investigating gene expression connectivity and provides more biologically-relevant results than

  8. Optical tests for using smartphones inside medical devices

    Science.gov (United States)

    Bernat, Amir S.; Acobas, Jennifer K.; Phang, Ye Shang; Hassan, David; Bolton, Frank J.; Levitz, David

    2018-02-01

    Smartphones are currently used in many medical applications and are more frequently being integrated into medical imaging devices. The regulatory requirements in existence today however, particularly the standardization of smartphone imaging through validation and verification testing, only partially cover imaging characteristics with a smartphone. Specifically, it has been shown that smartphone camera specifications are of sufficient quality for medical imaging, and there are devices which comply with the FDA's regulatory requirements for a medical device such as a device's field of view, direction of viewing and optical resolution and optical distortion. However, these regulatory requirements do not call specifically for color testing. Images of the same object using automatic settings or different light sources can show different color composition. Experimental results showing such differences are presented. Under some circumstances, such differences in color composition could potentially lead to incorrect diagnoses. It is therefore critical to control the smartphone camera and illumination parameters properly. This paper examines different smartphone camera settings that affect image quality and color composition. To test and select the correct settings, a test methodology is proposed. It aims at evaluating and testing image color correctness and white balance settings for mobile phones and LED light sources. Emphasis is placed on color consistency and deviation from gray values, specifically by evaluating the ΔC values based on the CIEL*a*b* color space. Results show that such standardization minimizes differences in color composition and thus could reduce the risk of a wrong diagnosis.

  9. Proposed Testing to Assess the Accuracy of Glass-To-Metal Seal Stress Analyses.

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, Robert S.; Emery, John M; Tandon, Rajan; Antoun, Bonnie R.; Stavig, Mark E.; Newton, Clay S.; Gibson, Cory S; Bencoe, Denise N.

    2014-09-01

    The material characterization tests conducted on 304L VAR stainless steel and Schott 8061 glass have provided higher fidelity data for calibration of material models used in Glass - T o - Metal (GTM) seal analyses. Specifically, a Thermo - Multi - Linear Elastic Plastic ( thermo - MLEP) material model has be en defined for S S304L and the Simplified Potential Energy Clock nonlinear visc oelastic model has been calibrated for the S8061 glass. To assess the accuracy of finite element stress analyses of GTM seals, a suite of tests are proposed to provide data for comparison to mo del predictions.

  10. 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.

  11. 78 FR 35273 - Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing...

    Science.gov (United States)

    2013-06-12

    ..., to FDA for approval to market a product in interstate commerce. The container and package labeling... be in electronic format and in a form that FDA can process, review, and archive. This requirement is... 356h ``Application to Market a New Drug, Biologic, or an Antibiotic Drug for Human Use'' to harmonize...

  12. Comparison of the cobas Human Papillomavirus (HPV) Test with the Hybrid Capture 2 and Linear Array HPV DNA Tests

    Science.gov (United States)

    Sadorra, Mark; LaMere, Brandon J.; Kail, Randi; Aldrich, Carrie; Kinney, Walter; Fetterman, Barbara; Lorey, Thomas; Schiffman, Mark; Castle, Philip E.

    2012-01-01

    The cobas human papillomavirus (HPV) test (cobas) was recently approved by the U.S. Food and Drug Administration (FDA) and identifies HPV16 and HPV18 separately as well as detecting a pool of 11 HR-HPV genotypes (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68) and also HPV66. We compared cobas, Linear Array (LA), and Hybrid Capture 2 (HC2) assays for detection of carcinogenic HPV DNA, and cobas and LA for detection of HPV16 and HPV18 DNA, among the first 1,852 women enrolled in the HPV Persistence and Progression Cohort (PaP Cohort) study. Specimens were tested by all 3 assays 1 year after an HC2-positive result. In 1,824 specimens with cobas results, cobas had an 85.9% agreement with HC2 and 91.0% agreement with LA for carcinogenic HPV detection. When results between cobas and HC2 disagreed, cobas tended to call more women HPV positive (P < 0.01). Categorizing cobas and LA results hierarchically according to cancer risk (HPV16, HPV18, other carcinogenic HPV genotypes, or carcinogen negative), there was a 90% agreement for all categories of HPV (n = 1,824). We found good agreement between the two U.S. FDA-approved HPV tests, with discrepancies between the two assays due to specific characteristics of the individual assays. Additional studies are needed to compare HC2 and cobas for detecting and predicting CIN3 to understand the clinical implications of the discrepant test results between the two tests. PMID:22075592

  13. 75 FR 34463 - Oversight of Laboratory Developed Tests; Public Meeting; Request for Comments

    Science.gov (United States)

    2010-06-17

    ... patient population. In addition, the components of traditional LDTs were regulated individually by FDA as... field creates a competitive disadvantage and potential disincentive to innovation by other manufacturers...) Challenges for Laboratories, (3) Direct to Consumer Marketing of Testing, and (4) Education and Outreach...

  14. 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

  15. Thematic Apperception Test: an original proposal for interaction analysis

    Directory of Open Access Journals (Sweden)

    Doriana Dipaola

    2015-12-01

    Full Text Available The TAT as projective technique gives the opportunity to explore the inner world and the intra-psychic functioning, as well as the objectual representations and the prevailing thinking processes. Our hypothesis is that the TAT could also be deployed as a valid tool in the analysis of inter-personal functioning, specifically within the couple. From this assumption originates our proposal for an original methodology of TAT deployment and reading, which integrates the classical individual TAT methodology with the Common Rorschach method suggested by Willi. The goal is to experiment a parallel utilisation of the test that could contribute to the understanding of personalities and of how these intertwine in couple interaction. “In the relationship with the partner, the personality takes new shapes, given personality and character traits are strengthened, while others lose importance”, (Theodore Lidz, in Willi, 1990. The couple TAT presupposes a sequence of pictures proposed following procedures identical to the Common Rorschach ones to the single individuals at first and then to the couple. From the initial individual task follows the one of building a commonly shared history starting from the stimulus. The suggested methodology shall be exemplified through the presentation of clinical cases belonging to the research sample. The comprehension of the inter-personal dynamic, in a common task, could allow to explore the ways in which conflict expresses itself, the roles and prospects for collaboration, the “generativity” of the couple and the management of affects and anxieties in the interaction and could be successfully deployed as a tool in the context of couple counselling.

  16. 77 FR 14022 - Guidance for Industry: Testing for Salmonella Species in Human Foods and Direct-Human-Contact...

    Science.gov (United States)

    2012-03-08

    ...-contact animal foods, and the interpretation of test results, when the presence of Salmonella spp. in the... eggs) and direct-human-contact animal foods, and the interpretation of test results, when the presence... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0091...

  17. Characterization of currently marketed heparin products: key tests for quality assurance.

    Science.gov (United States)

    Keire, David A; Ye, Hongping; Trehy, Michael L; Ye, Wei; Kolinski, Richard E; Westenberger, Benjamin J; Buhse, Lucinda F; Nasr, Moheb; Al-Hakim, Ali

    2011-01-01

    During the 2007-2008 heparin crisis, it was found that the United States Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS) in heparin. In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to not only detect the contaminant OSCS but also to improve assurance of quality and purity of the drug product. Additional tests were also developed to monitor the heparin supply chain for other possible economically motivated additives or impurities. In 2009, a new USP monograph was put in place that includes 500 MHz (1)H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time assays with purified factor IIa or factor Xa. These tests represent orthogonal approaches for UFH identification, measurement of bioactivity, and for detection of process impurities or contaminants in UFH. The FDA has applied these analytical approaches to the study of UFH active pharmaceutical ingredients in the marketplace. Here, we describe results from a comprehensive survey of UFH collected from seven different sources after the 2009 monograph revision and compare these data with results obtained on other heparin samples collected during the 2007-2008 crisis.

  18. Zero-inflated Poisson model based likelihood ratio test for drug safety signal detection.

    Science.gov (United States)

    Huang, Lan; Zheng, Dan; Zalkikar, Jyoti; Tiwari, Ram

    2017-02-01

    In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells.

  19. 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.

  20. Global dose to man from proposed NNTRP high altitude nuclear tests

    International Nuclear Information System (INIS)

    Peterson, K.R.

    1975-05-01

    Radionuclide measurements from past high altitude nuclear testing have enabled development of a model to estimate surface deposition and doses from 400 kt of fission products injected in winter within the Pacific Test Area at altitudes in excess of 50 km. The largest 30-year average dose to man is about 10 millirem and occurs at 30 0 to 50 0 N latitude. The principal contributor to this dose is external gamma radiation from gross fission products. Individual doses from 90 Sr via the forage-cow-milk pathway and 137 Cs via the pasture-meat pathway are about 1/5 the gross fission product doses. The global 30-year population dose is 3 x 10 7 person-rem, which compares with a 30-year natural background population dose of 1 X 10 10 person-rem. Due in large part to the global distribution of population, over 98 percent of the global person-rem from the proposed high altitude tests is received in the Northern Hemisphere, while about 75 percent of the total population dose occurs within the 30 0 --50 0 N latitude belt. Detonations in summer would decrease the global dose by about a factor of three. (U.S.)

  1. 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.

  2. Center for Cancer Research plays key role in first FDA-approved drug for treatment of Merkel cell carcinoma | Center for Cancer Research

    Science.gov (United States)

    The Center for Cancer Research’s ability to rapidly deploy integrated basic and clinical research teams at a single site facilitated the rapid FDA approval of the immunotherapy drug avelumab for metastatic Merkel cell carcinoma, a rare, aggressive form of skin cancer. Learn more...  

  3. The 2014 FDA assessment of commercial fish: practical considerations for improved dietary guidance.

    Science.gov (United States)

    McGuire, Jennifer; Kaplan, Jason; Lapolla, John; Kleiner, Rima

    2016-07-13

    The U.S. Food and Drug Administration (FDA) recently released its report: A Quantitative Assessment of the Net Effects on Fetal Neurodevelopment from Eating Commercial Fish (As Measured by IQ and also by Early Age Verbal Development in Children). By evaluating the benefits and potential concerns of eating fish during pregnancy and breastfeeding, the analysis suggests that pregnant women consuming two seafood meals (8-12 oz) per week could provide their child with an additional 3.3 IQ points by age 9. Recent insights from behavioral economics research indicate that other factors, such as concerns about price and methylmercury (MeHg) exposure, appear to reduce fish consumption in many individuals.To assess the net effects of eating commercial fish during pregnancy, we compared the consumption of select fish species necessary to achieve IQ benefits with the amount necessary to have adverse developmental effects due to MeHg exposure. For the species or market types evaluated, the number of servings necessary to reach MeHg exposure to observe an adverse effect was at least twice that the amount estimated to achieve peak developmental benefit. We then reported average costs of fresh and canned or pouched fish, and calculated the cost per week for pregnant women to achieve maximum IQ benefits for their gestating child. Canned light tuna was the least expensive option at $1.83 per week to achieve maximum IQ benefit.Due to their relatively low cost, canned and pouched fish products eaten with enough regularity are likely to provide peak cognitive benefits. Because of its popularity, canned and pouched tuna could provide some of the largest cognitive benefits from fish consumption in the U.S. Future FDA consumer advice and related educational initiatives could benefit from a broader perspective that highlights the importance of affordable and accessible fish choices. These observations underscore the importance of clear public health messaging that address both health

  4. European experiences of the proposed ASTM test method for crack arrest toughness of ferritic materials

    International Nuclear Information System (INIS)

    Jutla, T.; Lidbury, D.P.G.; Ziebs, J.; Zimmermann, C.

    1986-01-01

    The proposed ASTM test method for measuring the crack arrest toughness of ferritic materials using wedge-loaded, side-grooved, compact specimens was applied to three steels: A514 bridge steel, A588 bridge steel, and A533B pressure vessel steel. Five sets of results from different laboratories are discussed here. Notches were prepared by spark erosion, although root radii varied from ∝0.1-1.5 mm. Although fast fractures were successfully initiated, arrest did not occur in a significant number of cases. The results showed no obvious dependence of crack arrest toughness, K a , (determined by a static analysis) on crack initiation toughness, K 0 . It was found that K a decreases markedly with increasing crack jump distance. A limited amount of further work on smaller specimens of the A533B steel showed that lower K a values tended to be recorded. It is concluded that a number of points relating to the proposed test method and notch preparation are worthy of further consideration. It is pointed out that the proposed validity criteria may screen out lower bound data. Nevertheless, for present practical purposes, K a values may be regarded as useful in providing an estimate of arrest toughness - although not necessarily a conservative estimate. (orig./HP)

  5. Clinical relevance of the proposed sexual addiction diagnostic criteria: relation to the Sexual Addiction Screening Test-Revised.

    Science.gov (United States)

    Carnes, Patrick J; Hopkins, Tiffany A; Green, Bradley A

    2014-01-01

    The present article examines and compares the various diagnostic rubrics proposed to codify symptoms of sexual addiction, and then briefly summarizes the ongoing controversy on whether sexual addiction is a valid construct. Using the diagnostic criteria proposed by , the prevalence rate of each criterion is examined in terms of scores on the Sexual Addiction Screening Test-Revised scales (). Differences in diagnostic criteria endorsement associated with sex, sexual orientation, and setting were also explored. Results from a clinical sample of men and women seeking treatment for sexual addiction demonstrated clinical relevance of the criteria, in that all but 3 criteria are endorsed at more than 50% of participants screening positive for sexual addiction on the Sexual Addiction Screening Test-Revised. Sex differences were also noted for endorsement rates of several of the criteria. Finally, several proposed criteria may pose a higher clinical threshold and thus be utilized by clinicians to identify patients with increased pathology. Results are discussed in the context of existing diagnostic frameworks across etiological perspectives.

  6. 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.

  7. Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants.

    Science.gov (United States)

    Posner, Kelly; Oquendo, Maria A; Gould, Madelyn; Stanley, Barbara; Davies, Mark

    2007-07-01

    To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antidepressants conducted by the Food and Drug Administration (FDA). Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated. Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of "suicide attempt," a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89). Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA's audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all

  8. 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.

  9. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    International Nuclear Information System (INIS)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345–1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  10. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Kevin C., E-mail: ke@sc.edu [University of South Carolina, Department of Philosophy, USC NanoCenter (United States); Volz, David C. [University of South Carolina, Department of Environmental Health Sciences, Arnold School of Public Health (United States)

    2012-01-15

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  11. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Science.gov (United States)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  12. 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

  13. 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

  14. The proposed alignment system for the Final Focus Test Beam at SLAC

    International Nuclear Information System (INIS)

    Ruland, R.E.; Fischer, G.E.

    1990-09-01

    This report describes the current state of work in progress with respect to the geometry, alignment requirements, scenarios, and hardware for meeting the tolerances of the Final Focus Test Beam (FFTB) at SLAC. The methods and systems proposed acknowledge that component motion at the micron level, from whatever cause (ground motion, thermal effects, etc.) must be measured on-line and compensated for on relatively short time scales. To provide an integrated alignment/positioning package, some unique designs for reference systems, calibration of effect electric and magnetic centers, and component movers are introduced. 24 refs., 28 figs

  15. A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Ruoxing Yu

    Full Text Available Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat. D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium.

  16. Examination of solar simulators used for the determination of sunscreen UVA efficacy.

    Science.gov (United States)

    Sayre, Robert M; Dowdy, John C

    2010-01-01

    The U.S. FDA recently proposed both in vivo and in vitro UVA efficacy tests for sunscreen products with the lower result used to establish the sunscreen's labeled UVA protection claim. The FDA stated their rationale for dual tests was concern that the in vivo test method overemphasizes UVA-2 (320-340 nm) photoprotection. We attribute FDA's observation to the relative lack, compared to sunlight, of UVA-1 (340-400 nm) radiation in the current JCIA UVA solar simulator specification, allowing the method to generate higher UVA protection factors than sunscreens will provide in sunlight. Our work is based upon comparisons of Air Mass 1.0 sunlight to variously filtered UVA solar simulators. Sources near the JCIA UVA-2/UVA limits (8-20%) had a goodness of fit to solar UVA of only 67-79%. We propose that instead of using ratios of UVA-2 to UVA the standard should be a goodness of fit to the UVA region of an Air Mass 1 solar reference spectrum. As the spectral distribution of solar UVA varies much less than UVB, sunlight of reasonable zenith angles of < or = 60 degrees will have similar spectral shapes and approximate risk spectrum. Goodness of fit to this spectrum will produce UVA protection values predictive to those actually achieved in sunlight of different zenith angles.

  17. The FDA guidance for industry on PROs: the point of view of a pharmaceutical company.

    Science.gov (United States)

    Arpinelli, Fabio; Bamfi, Francesco

    2006-10-31

    The importance of the patients point of view on their health status is widely recognised. Patient-reported outcomes is a broad term encompassing a large variety of different health data reported by patients, as symptoms, functional status, Quality of Life and Health-Related Quality of Life. Measurements of Health-Related Quality of Life have been developed during many years of researches, and a lot of validated questionnaires exist. However, few attempts have been made to standardise the evaluation of instruments characteristics, no recommendations are made about interpretation on Health-Related Quality of Life results, especially regarding the clinical significance of a change leading a therapeutic approach. Moreover, the true value of Health-Related Quality of Life evaluations in clinical trials has not yet been completely defined. An important step towards a more structured and frequent use of Patient-Reported Outcomes in drug development is represented by the FDA Guidance, issued on February 2006. In our paper we aim to report some considerations on this Guidance. Our comments focus especially on the characteristics of instruments to use, the Minimal Important Difference, and the methods to calculate it. Furthermore, we present the advantages and opportunities of using the Patient-Reported Outcomes in drug development, as seen by a pharmaceutical company. The Patient-Reported Outcomes can provide additional data to make a drug more competitive than others of the same pharmacological class, and a well demonstrated positive impact on the patient' health status and daily life might allow a higher price and/or the inclusion in a reimbursement list. Applying extensively the FDA Guidance in the next trials could lead to a wider culture of subjective measurement, and to a greater consideration for the patient's opinions on his/her care. Moreover, prescribing doctors and payers could benefit from subjective information to better define the value of drugs.

  18. Experimental testing on free vibration behaviour for silicone rubbers proposed within lumbar disc prosthesis.

    Science.gov (United States)

    Rotaru, Iuliana; Bujoreanu, Carmen; Bele, Adrian; Cazacu, Maria; Olaru, Dumitru

    2014-09-01

    This research was focused on the damping capacity study of two types of silicone rubbers proposed as layers within total lumbar disc prostheses of ball-and-socket model. In order to investigate the damping capacity, the two silicone rubber types mainly differing by the molecular mass of polymeric matrix and the filler content, as was emphasized by scanning electron microscopy and differential scanning calorimetry, were subjected to free vibration testing. Using an adapted experimental installation, three kinds of damping testing were realised: tests without samples and tests with three samples of each type of silicone rubber (69 ShA and 99 ShA). The free vibration tests were performed at a frequency of about 6 Hz using a weight of 11.8 kg. The relative damping coefficient was determined by measuring of two successive amplitudes on the vibrogram and calculating of the logarithmic decrement. The test results with silicone rubber samples showed a relative damping coefficient of 0.058 and respectively 0.077, whilst test results without samples showed a relative damping coefficient of 0.042. These silicone rubbers were found to have acceptable damping properties to be used as layers placed inside the prosthetic components. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. A proposal for refining the forced swim test in Swiss mice.

    Science.gov (United States)

    Costa, Ana Paula Ramos; Vieira, Cintia; Bohner, Lauren O L; Silva, Cristiane Felisbino; Santos, Evelyn Cristina da Silva; De Lima, Thereza Christina Monteiro; Lino-de-Oliveira, Cilene

    2013-08-01

    The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab.

    Science.gov (United States)

    Velayudhan, Jyoti; Chen, Yuh-Feng; Rohrbach, Amanda; Pastula, Christina; Maher, Gwen; Thomas, Heather; Brown, Ryan; Born, Teresa L

    2016-08-01

    Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in structure and function may be expected during development of biosimilar mAbs. Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods. Any identified structural differences should not result in differences in biofunctional or clinical activity. A comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab (adalimumab [US]) and EU-authorized adalimumab (adalimumab [EU]) was conducted to demonstrate similarity in biofunctional activity. The functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α (TNFα) and relative binding to transmembrane TNFα. The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α (LTα)-induced chemokine production, and cytotoxicity was also tested. Binding to Fc-gamma receptors FcγRIa, FcγRIIa (131H), FcγRIIIa (158V and 158F), and neonatal Fc receptor (FcRn) was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The data demonstrate that ABP 501 is similar to both adalimumab (US) and adalimumab (EU) with respect to evaluated biofunctional activities. Similarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity. The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab (US), and adalimumab (EU) are likely to be clinically similar.

  1. 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

  2. Environmental assessment report: Nuclear Test Technology Complex. [Construction and operation of proposed facility

    Energy Technology Data Exchange (ETDEWEB)

    Tonnessen, K.; Tewes, H.A.

    1982-08-01

    The US Department of Energy (USDOE) is planning to construct and operate a structure, designated the Nuclear Test Technology Complex (NTTC), on a site located west of and adjacent to the Lawrence Livermore National Laboratory. The NTTC is designed to house 350 nuclear test program personnel, and will accommodate the needs of the entire staff of the continuing Nuclear Test Program (NTP). The project has three phases: land acquisition, facility construction and facility operation. The purpose of this environmental assessment report is to describe the activities associated with the three phases of the NTTC project and to evaluate potential environmental disruptions. The project site is located in a rural area of southeastern Alameda County, California, where the primary land use is agriculture; however, the County has zoned the area for industrial development. The environmental impacts of the project include surface disturbance, high noise levels, possible increases in site erosion, and decreased air quality. These impacts will occur primarily during the construction phase of the NTTC project and can be mitigated in part by measures proposed in this report.

  3. Proposal of a critical test of the Navier-Stokes-Fourier paradigm for compressible fluid continua

    Science.gov (United States)

    Brenner, Howard

    2013-01-01

    A critical, albeit simple experimental and/or molecular-dynamic (MD) simulation test is proposed whose outcome would, in principle, establish the viability of the Navier-Stokes-Fourier (NSF) equations for compressible fluid continua. The latter equation set, despite its longevity as constituting the fundamental paradigm of continuum fluid mechanics, has recently been criticized on the basis of its failure to properly incorporate volume transport phenomena—as embodied in the proposed bivelocity paradigm [H. Brenner, Int. J. Eng. Sci.IJESAN0020-722510.1016/j.ijengsci.2012.01.006 54, 67 (2012)]—into its formulation. Were the experimental or simulation results found to accord, even only qualitatively, with bivelocity predictions, the temperature distribution in a gas-filled, thermodynamically and mechanically isolated circular cylinder undergoing steady rigid-body rotation in an inertial reference frame would not be uniform; rather, the temperature would be higher at the cylinder wall than along the axis of rotation. This radial temperature nonuniformity contrasts with the uniformity of the temperature predicted by the NSF paradigm for these same circumstances. Easily attainable rates of rotation in centrifuges and readily available tools for measuring the expected temperature differences render experimental execution of the proposed scheme straightforward in principle. As such, measurement—via experiment or MD simulation—of, say, the temperature difference ΔT between the gas at the wall and along the axis of rotation would provide quantitative tests of both the NSF and bivelocity hydrodynamic models, whose respective solutions for the stated set of circumstances are derived in this paper. Independently of the correctness of the bivelocity model, any temperature difference observed during the proposed experiment or simulation, irrespective of magnitude, would preclude the possibility of the NSF paradigm being correct for fluid continua, except for

  4. Proposal of a critical test of the Navier-Stokes-Fourier paradigm for compressible fluid continua.

    Science.gov (United States)

    Brenner, Howard

    2013-01-01

    A critical, albeit simple experimental and/or molecular-dynamic (MD) simulation test is proposed whose outcome would, in principle, establish the viability of the Navier-Stokes-Fourier (NSF) equations for compressible fluid continua. The latter equation set, despite its longevity as constituting the fundamental paradigm of continuum fluid mechanics, has recently been criticized on the basis of its failure to properly incorporate volume transport phenomena-as embodied in the proposed bivelocity paradigm [H. Brenner, Int. J. Eng. Sci. 54, 67 (2012)]-into its formulation. Were the experimental or simulation results found to accord, even only qualitatively, with bivelocity predictions, the temperature distribution in a gas-filled, thermodynamically and mechanically isolated circular cylinder undergoing steady rigid-body rotation in an inertial reference frame would not be uniform; rather, the temperature would be higher at the cylinder wall than along the axis of rotation. This radial temperature nonuniformity contrasts with the uniformity of the temperature predicted by the NSF paradigm for these same circumstances. Easily attainable rates of rotation in centrifuges and readily available tools for measuring the expected temperature differences render experimental execution of the proposed scheme straightforward in principle. As such, measurement-via experiment or MD simulation-of, say, the temperature difference ΔT between the gas at the wall and along the axis of rotation would provide quantitative tests of both the NSF and bivelocity hydrodynamic models, whose respective solutions for the stated set of circumstances are derived in this paper. Independently of the correctness of the bivelocity model, any temperature difference observed during the proposed experiment or simulation, irrespective of magnitude, would preclude the possibility of the NSF paradigm being correct for fluid continua, except for incompressible flows.

  5. Implementation and test of proposals to integrate human factors in reporting and causal analysis in nuclear power plants

    International Nuclear Information System (INIS)

    Wilpert; Maimer, H.; Miller, R.; Fahlbruch, B.; Leiber, I.; Szameitat, S.; Baggen, R.; Gans, A.; Becker, G.

    1998-01-01

    The research project 'Implementation and Test of Proposals to integrate Human Factors in Reporting and Causal Analysis in Nuclear Power Plants' ('Implementation and Test', SR 2039/8) is based on two antecedent projects: 'Reporting System' (SR 2039/1) and 'Causal Analysis' (SR 2039/2). The project 'Implementation and Test' conducted various tests and introductory programs in cooperation with different target groups concerning the event analysis methodology 'SOL - Safety through Organizational Learning': Regulators, consultant organizations, union/works councillors and utilities. Thus, SOL was concurrently optimized and [apted for the practice in the German nuclear power industry. SOL was also validated in a German nuclear power plant using a concrete event. Results of the 'Implementation and Test' project demonstrate that SOL is fit to conduct event analyses practicably and economically with appropriate comprehensiveness and depth. SOL facilitates the identification of relevant contributing factors of events. This report concludes with various concrete proposals for the further development of the Program of the Federal Ministry of Environment, Nature Protection and Reactor Safety (BMU) and the Federal Agency of R[iation Protection (BfS) concerning 'The Contribution of Humans to Safety of Nuclear Power Plants'. (orig.) [de

  6. Disintegration of sublingual tablets: proposal for a validated test method and acceptance criterion.

    Science.gov (United States)

    Weda, M; van Riet-Nales, D A; van Aalst, P; de Kaste, D; Lekkerkerker, J F F

    2006-12-01

    In the Netherlands the market share of isosorbide dinitrate 5 mg sublingual tablets is dominated by 2 products (A and B). In the last few years complaints have been received from health care professionals on product B. During patient use the disintegration of the tablet was reported to be slow and/or incomplete, and ineffectiveness was experienced. In the European Pharmacopoeia (Ph. Eur.) no requirement is present for the disintegration time of sublingual tablets. The purpose of this study was to compare the in vitro disintegration time of products A and B, and to establish a suitable test method and acceptance criterion. A and B were tested with the Ph. Eur. method described in the monograph on disintegration of tablets and capsules as well as with 3 modified tests using the same Ph. Eur. apparatus, but without movement of the basket-rack assembly. In modified test 1 and modified test 2 water was used as medium (900 ml and 50 ml respectively), whereas in modified test 3 artificial saliva was used (50 ml). In addition, disintegration was tested in Nessler tubes with 0.5 and 2 ml of water. Finally, the Ph. Eur. method was also applied to other sublingual tablets with other drug substances on the Dutch market. With modified test 3 no disintegration could be achieved within 20 min. With the Ph. Eur. method and modified tests 1 and 2 product A and B differed significantly (p disintegration times. These 3 methods were capable of discriminating between products and between batches. The time measured with the Ph. Eur. method was significantly lower compared to modified tests 1 and 2 (p tablets the disintegration time should be tested. The Ph. Eur. method is considered suitable for this test. In view of the products currently on the market and taking into consideration requirements in the United States Pharmacopeia and Japanese Pharmacopoeia, an acceptance criterion of not more than 2 min is proposed.

  7. PROPOSAL FOR A MEASUREMENT MODEL FOR SOFTWARE TESTS WITH A FOCUS ON THE MANAGEMENT OF OUTSOURCED SERVICES

    Directory of Open Access Journals (Sweden)

    Angelica Toffano Seidel Calazans

    2012-08-01

    Full Text Available The need for outsourcing IT services has shown a significant growth over the past few years. This article presents a proposal for a measurement model for Software Tests with a focus on the management of these outsourced services by governmental organizations. The following specific goals were defined: to identify and analyze the test process; to identify and analyze the existing standards that govern the hiring of IT services and to propose a Measurement Model for outsourced services of this type. As to the analysis of the data collected (documentary research and semi-structured interviews, content analysis was adopted, and in order to prepare the metrics, the GQM – Goal, Questions, Metrics – approach was used. The result was confirmed by semi-structured interviews. Here is what the research identifies as possible: to establish objective and measurable criteria for a measurement size as the input to evaluate the efforts and deadlines involved; to follow up the test sub-processes and to evaluate the service quality. Therefore, the management of this type of service hiring can be done more efficiently.

  8. 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.

  9. Systematic review and proposal of a field-based physical fitness-test battery in preschool children: the PREFIT battery.

    Science.gov (United States)

    Ortega, Francisco B; Cadenas-Sánchez, Cristina; Sánchez-Delgado, Guillermo; Mora-González, José; Martínez-Téllez, Borja; Artero, Enrique G; Castro-Piñero, Jose; Labayen, Idoia; Chillón, Palma; Löf, Marie; Ruiz, Jonatan R

    2015-04-01

    Physical fitness is a powerful health marker in childhood and adolescence, and it is reasonable to think that it might be just as important in younger children, i.e. preschoolers. At the moment, researchers, clinicians and sport practitioners do not have enough information about which fitness tests are more reliable, valid and informative from the health point of view to be implemented in preschool children. Our aim was to systematically review the studies conducted in preschool children using field-based fitness tests, and examine their (1) reliability, (2) validity, and (3) relationship with health outcomes. Our ultimate goal was to propose a field-based physical fitness-test battery to be used in preschool children. PubMed and Web of Science. Studies conducted in healthy preschool children that included field-based fitness tests. When using PubMed, we included Medical Subject Heading (MeSH) terms to enhance the power of the search. A set of fitness-related terms were combined with 'child, preschool' [MeSH]. The same strategy and terms were used for Web of Science (except for the MeSH option). Since no previous reviews with a similar aim were identified, we searched for all articles published up to 1 April 2014 (no starting date). A total of 2,109 articles were identified, of which 22 articles were finally selected for this review. Most studies focused on reliability of the fitness tests (n = 21, 96%), while very few focused on validity (0 criterion-related validity and 4 (18%) convergent validity) or relationship with health outcomes (0 longitudinal and 1 (5%) cross-sectional study). Motor fitness, particularly balance, was the most studied fitness component, while cardiorespiratory fitness was the least studied. After analyzing the information retrieved in the current systematic review about fitness testing in preschool children, we propose the PREFIT battery, field-based FITness testing in PREschool children. The PREFIT battery is composed of the following

  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. The proposal of a novel software testing framework

    OpenAIRE

    Ahmad, Munib; Bajaber, Fuad; Qureshi, M. Rizwan Jameel

    2014-01-01

    Software testing is normally used to check the validity of a program. Test oracle performs an important role in software testing. The focus in this research is to perform class level test by introducing a testing framework. A technique is developed to generate test oracle for specification-based software testing using Vienna Development Method (VDM++) formal language. A three stage translation process, of VDM++ specifications of container classes to C++ test oracle classes, is described in th...

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. [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.

  17. 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.

  18. 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...

  19. 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

  20. 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.

  1. FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    Science.gov (United States)

    Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

    2015-11-01

    On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

  2. FDA Proposes New Safety Measures for Indoor Tanning Devices: The Facts

    Science.gov (United States)

    ... Related Consumer Updates Indoor Tanning: The Risks of Ultraviolet Rays 5 Tips for a Healthy Vacation More in Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food Medical Devices Nutrition Radiation-Emitting Products Tobacco Products ...

  3. 78 FR 47217 - Proposed Supervisory Guidance on Implementing Dodd-Frank Act Company-Run Stress Tests for Banking...

    Science.gov (United States)

    2013-08-05

    ... 10-50. More advanced portfolio segmentation can take several forms, such as by product (construction... CORPORATION 12 CFR Part 325 Proposed Supervisory Guidance on Implementing Dodd-Frank Act Company-Run Stress... 165(i)(2) of the Dodd-Frank Act Wall Street Reform and Consumer Protection Act (``DFA'') stress tests...

  4. General Electric Company proposed test and evaluation plan, commercial buildings. National Solar Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-04-01

    The general requirements and methods for instrumenting, testing, and evaluating solar HVAC systems forming a part of ERDA's ''Commercial Demonstration Program'' commensurate with ERDA 23A and the Proposed Management Plan 75SDS4270 are defined. Design requirements are specified for the performance of components and subsystems comprising the instrumentation and data gathering system, as well as the support functions required to perform the diagnostic measurements, collection and processing of data, and documentation of reports on solar HVAC system performance, including economic and societal evaluations.

  5. Point-Counterpoint: Cervical Cancer Screening Should Be Done by Primary Human Papillomavirus Testing with Genotyping and Reflex Cytology for Women over the Age of 25 Years

    Science.gov (United States)

    Zhao, Chengquan

    2015-01-01

    Screening for cervical cancer with cytology testing has been very effective in reducing cervical cancer in the United States. For decades, the approach was an annual Pap test. In 2000, the Hybrid Capture 2 human papillomavirus (HPV) test was approved by the U.S. Food and Drug Administration (FDA) for screening women who have atypical squamous cells of underdetermined significance (ASCUS) detected by Pap test to determine the need for colposcopy. In 2003, the FDA approved expanding the use of the test to include screening performed in conjunction with a Pap test for women over the age of 30 years, referred to as “cotesting.” Cotesting allows women to extend the testing interval to 3 years if both tests have negative results. In April of 2014, the FDA approved the use of an HPV test (the cobas HPV test) for primary cervical cancer screening for women over the age of 25 years, without the need for a concomitant Pap test. The approval recommended either colposcopy or a Pap test for patients with specific high-risk HPV types detected by the HPV test. This was based on the results of the ATHENA trial, which included more than 40,000 women. Reaction to this decision has been mixed. Supporters point to the fact that the primary-screening algorithm found more disease (cervical intraepithelial neoplasia 3 or worse [CIN3+]) and also found it earlier than did cytology or cotesting. Moreover, the positive predictive value and positive-likelihood ratio of the primary-screening algorithm were higher than those of cytology. Opponents of the decision prefer cotesting, as this approach detects more disease than the HPV test alone. In addition, the performance of this new algorithm has not been assessed in routine clinical use. Professional organizations will need to develop guidelines that incorporate this testing algorithm. In this Point-Counterpoint, Dr. Stoler explains why he favors the primary-screening algorithm, while Drs. Austin and Zhao explain why they prefer the

  6. An evaluation of the proposed tests with radioactive waste at WIPP

    International Nuclear Information System (INIS)

    Chaturvedi, L.; Silva, M.

    1992-01-01

    This paper discusses the Waste Isolation Pilot Plant (WIPP) a planned repository for permanent disposal of transuranic (TRU) radiative waste that has resulted from the defense activities of the U.S. Government over the past 50 years. Only the waste that is currently stored in an easily retrievable mode at ten U.S. Department of Energy (DOE) laboratories around the country will be shipped to WIPP. The waste consists of various kinds of trash including paper, rubber, rags and metal that is contaminated with radionuclides with very long half-lives. The decision to dispose of the waste permanently will be made based on projections of the behavior of the waste and the repository of 10,000 years or more. DOE has proposed shipping a limited amount of waste to WIPP for a five year Test Phase to demonstrating compliance with the U.S. Environmental Protection Agency (EPA) Standard for long-term isolation

  7. 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

  8. 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

  9. 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

  10. Mathematical evaluation of similarity factor using various weighing approaches on aceclofenac marketed formulations by model-independent method.

    Science.gov (United States)

    Soni, T G; Desai, J U; Nagda, C D; Gandhi, T R; Chotai, N P

    2008-01-01

    The US Food and Drug Administration's (FDA's) guidance for industry on dissolution testing of immediate-release solid oral dosage forms describes that drug dissolution may be the rate limiting step for drug absorption in the case of low solubility/high permeability drugs (BCS class II drugs). US FDA Guidance describes the model-independent mathematical approach proposed by Moore and Flanner for calculating a similarity factor (f2) of dissolution across a suitable time interval. In the present study, the similarity factor was calculated on dissolution data of two marketed aceclofenac tablets (a BCS class II drug) using various weighing approaches proposed by Gohel et al. The proposed approaches were compared with a conventional approach (W = 1). On the basis of consideration of variability, preference is given in the order of approach 3 > approach 2 > approach 1 as approach 3 considers batch-to-batch as well as within-samples variability and shows best similarity profile. Approach 2 considers batch-to batch variability with higher specificity than approach 1.

  11. The ecological sustainability trigon - A proposed conceptual framework for creating and testing management scenarios

    International Nuclear Information System (INIS)

    Marques, J.C.; Basset, A.; Brey, T.; Elliott, M.

    2009-01-01

    The ability to achieve ecological sustainability and the sustainable development of marine and estuarine ecosystems constitutes a complex major challenge and depends on many driving forces, often conflicting with each other. In particular, there are three major drivers: (a) the search for human well-being, health and safety, (b) the maintenance of ecological sustainability and environmental equilibrium, and (c) the tolerance of an increasing human population pressure and demand for wealth creation. We propose here the use of a conceptual guidance tool - the ecological sustainability trigon (EST) - as a means of building and testing environmental management scenarios. Although it requires further testing, the EST allows us to (a) address those three major drivers using human society view as a common currency, and (b) describe our behaviour, energetics (economy) and dynamics through ecological theory. Moreover, the EST appears promising for gap analysis and the means to address new research questions.

  12. 76 FR 48751 - Lanxess Corp.; Filing of Food Additive Petition (Animal Use); Calcium Formate

    Science.gov (United States)

    2011-08-09

    .... FDA-2011-F-0549] Lanxess Corp.; Filing of Food Additive Petition (Animal Use); Calcium Formate AGENCY... Administration (FDA) is announcing that Lanxess Corp. has filed a petition proposing that the food additive..., PA 15275-1112. The petition proposes to amend the food additive regulations in part 573 Food...

  13. 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.

  14. The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

    Science.gov (United States)

    Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

    2014-11-01

    Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

  15. No 3025. Proposal of law aiming at the acknowledgement and indemnification of the people victim of nuclear tests or accidents

    International Nuclear Information System (INIS)

    Taubira, Ch.; Giacobbi, P.; Ayrault, J.M.; Lurel, V.; Montebourg, A.; Dosiere, R.; Floch, J.; Adam, P.; Andrieux, S.; Aubron, J.M.; Bacquet, J.P.; Bapt, G.; Bascou, J.; Beauchaud, J.C.; Blazy, J.P.; Blisko, S.; Bloche, P.; Bois, J.C.; Boisserie, D.; Bourguignon, P.; Bousquet, D.; Carcenac, Th.; Carrillon-Couvreur, M.; Charzat, M.; Claeys, A.; Cohen, P.; Darciaux, C.; Dasseux, M.; David, M.; Dehoux, M.; Derosier, B.; Dolez, M.; Dose, F.; Ducout, P.; Dufau, J.P.; Dumas, W.; Dumont, J.L.; Dupre, J.P.; Durand, Y.; Duriez, O.; Emmanuelli, H.; Facon, A.; Francaix, M.; Gaillard, G.; Gautier, N.; Genisson, C.; Giraud, J.; Guinchard, P.; Habib, D.; Hoffman-Rispal, D.; Imbert, F.; Jalton, E.; Janquin, S.; Kucheida, J.P.; Lacuey, C.; Lambert, J.; Lamy, F.; Lang, J.; Le Bouillonnec, J.Y.; Le Bris, G.; Le Garrec, J.; Le Roux, B.; Lebranchu, M.; Lemasle, P.; Lepetit, A.; Leroy, J.C.; Liebgott, M.; Lignieres-Cassou, M.; Loncle, F.; Madrelle, B.; Masse, Ch.; Mathus, D.; Migaud, D.; Mignon, H.; Nayrou, H.; Neri, A.; Oget, M.R.; Paul, Ch.; Perez, J.C.; Perol-Dumont, M.F.

    2006-04-01

    This proposal of law aims at establishing the presumption of a relation between nuclear tests or accidents with the pathologies developed later on by the people present at that time in the contaminated areas. The proposal aims also at establishing an equality among the victims and at making up the juridical framework necessary for the government to proceed to the compensation of victims damages. (J.S.)

  16. Testing a SEA methodology for the energy sector: a waste incineration tax proposal

    International Nuclear Information System (INIS)

    Nilsson, Maans; Bjoerklund, Anna; Finnveden, Goeran; Johansson, Jessica

    2005-01-01

    Most Strategic Environmental Assessment (SEA) research has been preoccupied with SEA as a procedure and there are relatively few developments and tests of analytical methodologies. This paper applies and tests an analytical framework for an energy sector SEA. In a case study on a policy proposal for waste-to-energy taxation in Sweden, it studies changes in the energy system as a result of implementing the suggested tax by testing three analytical pathways: an LCA pathway, a site-dependent pathway, and a qualitative pathway. In addition, several valuation methods are applied. The assessment indicates that there are some overall environmental benefits to introducing a tax, but that benefits are modest compared to the potential. The methods are discussed in relation to characteristics for effective policy learning and knowledge uptake. The application shows that in many ways they complement each other rather than substitute for each other. The qualitative pathway is useful for raising awareness and getting a comprehensive view of environmental issues, but has limited potential for decision support. The precision increased as we went to LCA and to site-dependent analysis, and a hierarchy emerged in which the qualitative pathway filled rudimentary functions whereas the site-dependent analysis gave more advanced decision support. All methods had limited potential in supporting a choice between alternatives unless data was aggregated through a valuation exercise

  17. 76 FR 37690 - CooperVision, Inc.; Filing of Color Additive Petitions

    Science.gov (United States)

    2011-06-28

    ... color additives are intended to be copolymerized with various monomers for use as colored contact lens.... FDA-2011-C-0344 and FDA-2011-C-0463] CooperVision, Inc.; Filing of Color Additive Petitions AGENCY... Administration (FDA) is announcing that CooperVision, Inc., has filed two petitions proposing that the color...

  18. 4th Global CRO Council for Bioanalysis: coadministered drugs stability, EMA/US FDA guidelines, 483s and carryover.

    Science.gov (United States)

    Lowes, Steve; Jersey, Jim; Shoup, Ronald; Garofolo, Fabio; Needham, Shane; Couerbe, Philippe; Lansing, Tim; Bhatti, Masood; Sheldon, Curtis; Hayes, Roger; Islam, Rafiq; Lin, Zhongping; Garofolo, Wei; Moussallie, Marc; Teixeira, Leonardo de Souza; Rocha, Thais; Jardieu, Paula; Truog, James; Lin, Jenny; Lundberg, Richard; Breau, Alan; Dilger, Carmen; Bouhajib, Mohammed; Levesque, Ann; Gagnon-Carignan, Sofi; Jenkins, Rand; Nicholson, Robert; Lin, Ming Hung; Karnik, Shane; DeMaio, William; Smith, Kirk; Cojocaru, Laura; Allen, Mike; Fatmi, Saadya; Sayyarpour, Farhad; Malone, Michele; Fang, Xinping

    2012-04-01

    The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed.

  19. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

    Science.gov (United States)

    Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-08-01

    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." 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. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  20. 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.

  1. Harnessing scientific literature reports for pharmacovigilance. Prototype software analytical tool development and usability testing.

    Science.gov (United States)

    Sorbello, Alfred; Ripple, Anna; Tonning, Joseph; Munoz, Monica; Hasan, Rashedul; Ly, Thomas; Francis, Henry; Bodenreider, Olivier

    2017-03-22

    We seek to develop a prototype software analytical tool to augment FDA regulatory reviewers' capacity to harness scientific literature reports in PubMed/MEDLINE for pharmacovigilance and adverse drug event (ADE) safety signal detection. We also aim to gather feedback through usability testing to assess design, performance, and user satisfaction with the tool. A prototype, open source, web-based, software analytical tool generated statistical disproportionality data mining signal scores and dynamic visual analytics for ADE safety signal detection and management. We leveraged Medical Subject Heading (MeSH) indexing terms assigned to published citations in PubMed/MEDLINE to generate candidate drug-adverse event pairs for quantitative data mining. Six FDA regulatory reviewers participated in usability testing by employing the tool as part of their ongoing real-life pharmacovigilance activities to provide subjective feedback on its practical impact, added value, and fitness for use. All usability test participants cited the tool's ease of learning, ease of use, and generation of quantitative ADE safety signals, some of which corresponded to known established adverse drug reactions. Potential concerns included the comparability of the tool's automated literature search relative to a manual 'all fields' PubMed search, missing drugs and adverse event terms, interpretation of signal scores, and integration with existing computer-based analytical tools. Usability testing demonstrated that this novel tool can automate the detection of ADE safety signals from published literature reports. Various mitigation strategies are described to foster improvements in design, productivity, and end user satisfaction.

  2. Determination of total galactose from dried blood spots—extensive assay evaluation of a CE-marked test-kit

    OpenAIRE

    Fingerhut, R; Torresani, T

    2013-01-01

    Most newborn screening laboratories use CE-marked or FDA-approved test-kits, like in routine clinical chemistry. National regulations require only minimal evaluation from the customer, if the test-kits are used as specified by the manufacturer. The microtiter-based kit-concept is often based on the perception, that the laboratory always processes whole microtiter plates. However, in the daily routine, this is rather a rare exception, which leads to much higher costs per newborn, compared to t...

  3. Testing Proposed Correlations Between Olduvai Gorge and Laetoli, Tanzania Using Tephra Composition

    Science.gov (United States)

    McHenry, L. J.

    2006-12-01

    Olduvai Gorge and Laetoli are well-known Plio-Pleistocene archaeological sites located 30 km apart in Tanzania. Both received volcanic input from the nearby Ngorongoro Volcanic Highlands (NVH), and together provide a sedimentary and volcanic record from about 4.3 Ma to the Holocene. Previous researchers have proposed likely temporal correlations between the two sites, using both faunal and volcanic evidence. Direct tephra correlation between these sites could create a regional stratigraphic framework for their fossil and paleoecological records. Here, one of the proposed correlations is tested using geochemical fingerprinting. The fossiliferous Laetolil and Ndolanya beds of Laetoli predate the deposition of the Olduvai Beds, however recent 39Ar/40Ar SCLF age dating has shown potential temporal overlap between the Naibadad (2.23-1.93 +/- 0.02; Mangea, 1993) and Olpiro Beds (2.06-2.01 +/- 0.03; Manega 1993) at Laetoli with the Naabi Ignimbrite (2.029 +/- 0.005 Ma, Walter et al. 1992) and lower Bed I at Olduvai. Both the Naibadad bed and lower Bed I also contain fresh quartz-bearing tephra, which can be used for geochemical correlation. Three Naibadad tuffs and five lower Bed I tuffs (Naabi Ignimbrite, coarse feldspar crystal tuff (CFCT), Tuff IA, and two ignimbrites near Ngorongoro) were analyzed by electron microprobe for phenocryst and glass composition and compared to test for possible correlations. Certain mineralogical features made such a correlation unlikely. None of the lower Bed I tuffs analyzed contain significant plagioclase, which is present in all of the Naibadad tuffs analyzed. One Naibadad tuff has a bimodal glass composition indistinguishable from the CFCT, however the CFCT is rich in hornblende, while this Naibadad tuff contains none. This mineralogical difference highlights the need for mineralogical in addition to glass geochemical data for tephra correlation. Ngorongoro crater is the likely source for the Naibadad and lower Bed I tuffs because it

  4. 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.

  5. Syndromic Panel-Based Testing in Clinical Microbiology.

    Science.gov (United States)

    Ramanan, Poornima; Bryson, Alexandra L; Binnicker, Matthew J; Pritt, Bobbi S; Patel, Robin

    2018-01-01

    The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation. Copyright © 2017 American Society for Microbiology.

  6. PROPOSAL FOR BUILD A TEST STAND TO THE STUDY WATER RAM BASED ON THE RECOMMENDATIONS CONSTRUCTION

    Directory of Open Access Journals (Sweden)

    Dariusz GRYGO

    2016-05-01

    Full Text Available The main aim of this article was developed of a test stand to a study physics phenomena accruing at work in a ram water based on the construction recommendations. The experience gained by a number of attempts allowed to the developed construction recommendations that allowed to adjust the test stand to perform various studies of physics phenomena occurring at the work of water ram and easy adaptions to the new requirements. The article includes: the review of the test stands on which performed the study in the history and in the present times, description of the construction recommendations of the universal test stand and the proposal of the test stand developed based on the construction recommendations. Motivation to take up this issue follows from the interest of devices that work in an unconventional way, devices used a renewable energy that can be used in household e.g. to improve their energy balance, delivery water to houses, drinking water for animals, fields irrigation, etc. Analysis of the literature of the water ram, test stands and their performance shown that it is small and typically old development in popular science form. In times of intensive search new sources of renewable energy reactivation of this type equipment may be highly probable.

  7. Equations of motion of interacting massless fields of all spins as a free differential algebra

    Energy Technology Data Exchange (ETDEWEB)

    Vasiliev, M A

    1988-08-11

    It is argued that the equations of motion of interacting massless fields of all spins s=0, 1, ..., infinity can naturally be formulated in terms of a free differential algebra (FDA) constructed from one-forms and zero-forms that belong both to the adjoint representation of the infinite-dimensional superalgebra of higher spins and auxiliary fields proposed previously. This FDA is found explicitly in the first non-trivial order in the zero-forms. Various properties of the proposed FDA are discussed including the ways for incorporating internal (Yang-Mills) gauge symmetries via associative algebras.

  8. Rational Selection, Criticality Assessment, and Tiering of Quality Attributes and Test Methods for Analytical Similarity Evaluation of Biosimilars.

    Science.gov (United States)

    Vandekerckhove, Kristof; Seidl, Andreas; Gutka, Hiten; Kumar, Manish; Gratzl, Gyöngyi; Keire, David; Coffey, Todd; Kuehne, Henriette

    2018-05-10

    Leading regulatory agencies recommend biosimilar assessment to proceed in a stepwise fashion, starting with a detailed analytical comparison of the structural and functional properties of the proposed biosimilar and reference product. The degree of analytical similarity determines the degree of residual uncertainty that must be addressed through downstream in vivo studies. Substantive evidence of similarity from comprehensive analytical testing may justify a targeted clinical development plan, and thus enable a shorter path to licensing. The importance of a careful design of the analytical similarity study program therefore should not be underestimated. Designing a state-of-the-art analytical similarity study meeting current regulatory requirements in regions such as the USA and EU requires a methodical approach, consisting of specific steps that far precede the work on the actual analytical study protocol. This white paper discusses scientific and methodological considerations on the process of attribute and test method selection, criticality assessment, and subsequent assignment of analytical measures to US FDA's three tiers of analytical similarity assessment. Case examples of selection of critical quality attributes and analytical methods for similarity exercises are provided to illustrate the practical implementation of the principles discussed.

  9. The strong Bell inequalities: A proposed experimental test

    Science.gov (United States)

    Fry, Edward S.

    1994-01-01

    All previous experimental tests of Bell inequalities have required additional assumptions. The strong Bell inequalities (i.e. those requiring no additional assumptions) have never been tested. An experiment has been designed that can, for the first time, provide a definitive test of the strong Bell inequalities. Not only will the detector efficiency loophole be closed; but the locality condition will also be rigorously enforced. The experiment involves producing two Hg-199 atoms by a resonant Raman dissociation of a mercury dimer ((199)Hg2) that is in an electronic and nuclear spin singlet state. Bell inequalities can be tested by measuring angular momentum correlations between the spin one-half nuclei of the two Hg-199 atoms. The method used to make these latter measurements will be described.

  10. Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.

    Science.gov (United States)

    Saps, M; Lavigne, J V

    2015-06-01

    The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children. 80 children with functional abdominal pain participated in a study of the efficacy of amitriptyline. Endpoints included patient-reported estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum clinically important difference in pain report was calculated as (i) mean change in VAS score for children reporting being 'better'; (ii) percent changes in pain (≥30% and ≥50%) on the VAS; and (iii) statistically reliable changes on the VAS for 68% and 95% confidence intervals. There was poor agreement between the three approaches. 43.6% of the children who met the FDA ≥30% criterion for clinically significant change did not achieve a reliable level of improvement (95% confidence interval). Children's self-reported ratings of being better may not be statistically reliable. A combined approach in which children must report improvement as better and achieve a statistically significant change may be more appropriate for outcomes in clinical trials. © 2015 John Wiley & Sons Ltd.

  11. Analysis of the Risks and Benefits of New Chemical Entities Approved by the US Food and Drug Administration (FDA) and Subsequently Withdrawn From the US Market.

    Science.gov (United States)

    Patriarca, Peter A; Van Auken, R Michael; Kebschull, Scott A

    2018-01-01

    Benefit-risk evaluations of drugs have been conducted since the introduction of modern regulatory systems more than 50 years ago. Such judgments are typically made on the basis of qualitative or semiquantitative approaches, often without the aid of quantitative assessment methods, the latter having often been applied asymmetrically to place emphasis on benefit more so than harm. In an effort to preliminarily evaluate the utility of lives lost or saved, or quality-adjusted life-years (QALY) lost and gained as a means of quantitatively assessing the potential benefits and risks of a new chemical entity, we focused our attention on the unique scenario in which a drug was initially approved based on one set of data, but later withdrawn from the market based on a second set of data. In this analysis, a dimensionless risk to benefit ratio was calculated in each instance, based on the risk and benefit quantified in similar units. The results indicated that FDA decisions to approve the drug corresponded to risk to benefit ratios less than or equal to 0.136, and that decisions to withdraw the drug from the US market corresponded to risk to benefit ratios greater than or equal to 0.092. The probability of FDA approval was then estimated using logistic regression analysis. The results of this analysis indicated that there was a 50% probability of FDA approval if the risk to benefit ratio was 0.121, and that the probability approaches 100% for values much less than 0.121, and the probability approaches 0% for values much greater than 0.121. The large uncertainty in these estimates due to the small sample size and overlapping data may be addressed in the future by applying the methodology to other drugs.

  12. Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: A population-based study.

    Science.gov (United States)

    Zhu, Ping; Du, Xianglin L; Lu, Guangrong; Zhu, Jay-Jiguang

    2017-07-04

    Few population-based analyses have investigated survival change in glioblastoma multiforme (GBM) patients treated with concomitant radiotherapy-temozolomide (RT-TMZ) and adjuvant temozolomide (TMZ) and then bevacizumab (BEV) after Food and Drug Administration (FDA) approval, respectively. We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general GBM population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. A total of 28933 GBM patients from SEER (N = 24578) and TCR (N = 4355) between January 2000 and December 2013 were included. Patients were grouped into three calendar periods based on date of diagnosis: pre-RT-TMZ and pre-BEV (1/2000-2/2005, P1), post-RT-TMZ and pre-BEV (3/2005-4/2009, P2), and post-RT-TMZ and post-BEV (5/2009-12/2013, P3). The association between calendar period of diagnosis and survival was analyzed in SEER and TCR, separately, by the Kaplan-Meier method and Cox proportional hazards model. We found a significant increase in median overall survival (OS) across the three periods in both populations. In multivariate models, the risk of death was significantly reduced during P2 and further decreased in P3, which remained unchanged after stratification. Comparison and validation analysis were performed in the combined dataset, and consistent results were observed. We conclude that the OS of GBM patients in a "real-world" setting has been steadily improved from January 2000 to December 2013, which likely resulted from the administrations of TMZ concomitant with RT and adjuvant TMZ for newly diagnosed GBM and then BEV for recurrent GBM after respective FDA approval.

  13. 76 FR 77837 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental...

    Science.gov (United States)

    2011-12-14

    ..., Drug, and Cosmetic Act (FD&C Act) to grant FDA authority to regulate the manufacture, marketing, and... consequences will be assessed by measuring respondents' susceptibility to initiation of tobacco use, motivation...

  14. 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.

  15. Time to rethink: an evidence-based response from pelvic surgeons to the FDA Safety Communication: "UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse".

    Science.gov (United States)

    Murphy, Miles; Holzberg, Adam; van Raalte, Heather; Kohli, Neeraj; Goldman, Howard B; Lucente, Vincent

    2012-01-01

    In July of 2011 the U.S. Food and Drug Administration (FDA) released a safety communication entitled "UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse." The stated purpose of this communication is to inform health care providers and patients that serious complications with placement of this mesh are not rare and that it is not clear that these repairs are more effective than nonmesh repair. The comments regarding efficacy are based on a systematic review of the scientific literature from 1996-2011 conducted by the FDA. Our review of the literature during this time yields some different conclusions regarding the safety and efficacy of mesh use in prolapse repair. It may be useful to consider this information prior to making recommendations regarding mesh use in prolapse surgery according to the recent UPDATE.

  16. 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.

  17. FDA-iRISK--a comparative risk assessment system for evaluating and ranking food-hazard pairs: case studies on microbial hazards.

    Science.gov (United States)

    Chen, Yuhuan; Dennis, Sherri B; Hartnett, Emma; Paoli, Greg; Pouillot, Régis; Ruthman, Todd; Wilson, Margaret

    2013-03-01

    Stakeholders in the system of food safety, in particular federal agencies, need evidence-based, transparent, and rigorous approaches to estimate and compare the risk of foodborne illness from microbial and chemical hazards and the public health impact of interventions. FDA-iRISK (referred to here as iRISK), a Web-based quantitative risk assessment system, was developed to meet this need. The modeling tool enables users to assess, compare, and rank the risks posed by multiple food-hazard pairs at all stages of the food supply system, from primary production, through manufacturing and processing, to retail distribution and, ultimately, to the consumer. Using standard data entry templates, built-in mathematical functions, and Monte Carlo simulation techniques, iRISK integrates data and assumptions from seven components: the food, the hazard, the population of consumers, process models describing the introduction and fate of the hazard up to the point of consumption, consumption patterns, dose-response curves, and health effects. Beyond risk ranking, iRISK enables users to estimate and compare the impact of interventions and control measures on public health risk. iRISK provides estimates of the impact of proposed interventions in various ways, including changes in the mean risk of illness and burden of disease metrics, such as losses in disability-adjusted life years. Case studies for Listeria monocytogenes and Salmonella were developed to demonstrate the application of iRISK for the estimation of risks and the impact of interventions for microbial hazards. iRISK was made available to the public at http://irisk.foodrisk.org in October 2012.

  18. 75 FR 20603 - Agency Information Collection Activities; Proposed Collection; Comment Request; Tobacco Health...

    Science.gov (United States)

    2010-04-20

    ... granted FDA important new authority to regulate the manufacture, marketing, and distribution of tobacco..., behavioral, or physiologic effects of current or future tobacco products, their constituents (including smoke...

  19. Proposal for an Accelerator R&D User Facility at Fermilab's Advanced Superconducting Test Accelerator (ASTA)

    Energy Technology Data Exchange (ETDEWEB)

    Church, M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Edwards, H. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Harms, E. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Henderson, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Holmes, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Lumpkin, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Kephart, R. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Levedev, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Leibfritz, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Nagaitsev, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Piot, P. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Northern Illinois Univ., DeKalb, IL (United States); Prokop, C. [Northern Illinois Univ., DeKalb, IL (United States); Shiltsev, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Sun, Y. E. [Argonne National Lab. (ANL), Argonne, IL (United States); Valishev, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2013-10-01

    Fermilab is the nation’s particle physics laboratory, supported by the DOE Office of High Energy Physics (OHEP). Fermilab is a world leader in accelerators, with a demonstrated track-record— spanning four decades—of excellence in accelerator science and technology. We describe the significant opportunity to complete, in a highly leveraged manner, a unique accelerator research facility that supports the broad strategic goals in accelerator science and technology within the OHEP. While the US accelerator-based HEP program is oriented toward the Intensity Frontier, which requires modern superconducting linear accelerators and advanced highintensity storage rings, there are no accelerator test facilities that support the accelerator science of the Intensity Frontier. Further, nearly all proposed future accelerators for Discovery Science will rely on superconducting radiofrequency (SRF) acceleration, yet there are no dedicated test facilities to study SRF capabilities for beam acceleration and manipulation in prototypic conditions. Finally, there are a wide range of experiments and research programs beyond particle physics that require the unique beam parameters that will only be available at Fermilab’s Advanced Superconducting Test Accelerator (ASTA). To address these needs we submit this proposal for an Accelerator R&D User Facility at ASTA. The ASTA program is based on the capability provided by an SRF linac (which provides electron beams from 50 MeV to nearly 1 GeV) and a small storage ring (with the ability to store either electrons or protons) to enable a broad range of beam-based experiments to study fundamental limitations to beam intensity and to develop transformative approaches to particle-beam generation, acceleration and manipulation which cannot be done elsewhere. It will also establish a unique resource for R&D towards Energy Frontier facilities and a test-bed for SRF accelerators and high brightness beam applications in support of the OHEP

  20. The effect of proposed crush tests on transport containers

    International Nuclear Information System (INIS)

    1984-09-01

    Crush tests were performed on two AECL F112 packaging specimens, two simulated AECL-CRNL 4H packaging specimens, and on empty steel drums. The 9 m drop test was carried out on two simulated AECL-CRNL 4H packaging specimens for comparison with the effects of the crush test. The tests were filmed using high speed photography and 35mm still photographs

  1. COMPASS-II Proposal

    CERN Document Server

    Gautheron, F; Koivuniemi, J; Meyer, W; Reicherz, G; Bisplinghoff, J; Eversheim, D; Hinterberger, F; Jahn, R; Joosten, R; Negrini, T; Barth, J; Klein, F; Goertz, S; Panknin, R; Pretz, J; Windmolders, R; Srnka, A; Dasgupta, S; Dhara, L; Sarkara, S; Sinha, L; Alexakhin, V Yu; Alexeev, G D; Anosov, V A; Antonov, A; Efremov, A; Gavrichtchouk, O P; Guskov, A; Ivanshin, Yu; Ivanov, O; Kisselev, Yu; Kouznetsov, O; Kroumchtein, Z; Meshcheryakov, G V; Nagaytsev, A; Olshevski, A; Peshekhonov, D V; Pontecorvo, G; Rossiyskaya, N; Sapozhnikov, M G; Savin, I A; Shevchenko, O Yu; Sissakian, A N; Smirnov, G I; Teryaev, O V; Tkatchev, L G; Vlassov, N V; Zemlyanichkina, E; Adolph, Ch; Braun, Ch; Eyrich, W; Lehmann, A; Richter, A; Fischer, H; Heinsius, F-H; Herrmann, F; Guthörl, T; Lauser, L; Königsmann, K; Nerling, F; Schill, Ch; Wollny, H; Schmidt, K; Schopferer, S; Mallot, G K; Nowak, W-D; Schönning, K; Schott, M; Sulc, M; Bordalo, P; Franco, C; Nunes, A S; Quintans, C; Ramos, S; Silva, L; Stolarski, M; Bernhard, J; Chaberny, D; du Fresne von Hohenesche, N; von Harrach, D; Jasinski, P; Kabuß, E M; Kang, D-H; Ostrick, M; Pochodzalla, J; Alexandrov, Yu; Zavertyaev, M; Böhmer, F; Dørheim, S; Friedrich, J M; Gerassimov, S; Grabmüller, S; Grube, B; Haas, F; Höppner, Ch; Ketzer, B; Konorov, I; Krämer, M; Mann, A; Nagel, T; Neubert, S; Paul, S; Schmitt, L; Uhl, S; Bettinelli, M; Dünnweber, W; Faessler, M A; Geyer, R; Rajotte, J-F; Schlüter, T; Uman, I; Zvyagin, A; Finger, M; Finger jr, M; Slunecka, M; Jary, V; Virius, M; Donskov, S V; Filin, A; Khaustov, G V; Khokhlov, Yu; Kolosov, V; Konstantinov, V; Lednev, A A; Mikhailov, Yu V; Nikolaenko, V I; Polyakov, V A; Ryabchikov, D; Samoylenko, V D; Bedfer, Y; Burtin, E; Ferrero, A; d’Hose, N; Kunne, F; Magnon, A; Makke, N; Marchand, C; Morreale, A; Neyret, D; Platchkov, S; Vandenbroucke, M; Lichtenstadt, J; Moinester, M A; Birsa, R; Bradamante, F; Bressan, A; Dalla Torre, S; Duic, V; Elia, C; Giorgi, M; Gobbo, B; Levorato, S; Martin, A; Pesaro, G; Rocco, E; Sbrizzai, G; Schiavon, P; Sozzi, F; Tessaro, S; Tessarotto, F; Alexeev, M G; Amoroso, A; Balestra, F; Bertini, R; Chiosso, M; Denisov, O; Garfagnini, R; Gnesi, I; Grasso, A; Kotzinian, A; Maggiora, A; Melis, S; Panzieri, D; Parsamyan, B; Piragino, G; Sosio, S; Takekawa, S; Badelek, B; Brona, G; Gazda, R; Klimaszewski, K; Kurek, K; Rondio, E; Sandacz, A; Sznajder, P; Wislicki, W; Marzec, J; Dziewiecki, M; Sulej, R; Zaremba, K; Ziembicki, M; Doshita, N; Iwata, T; Ishimoto, S; Horikawa, N; Kondo, K; Matsuda, T; Miyachi, Y

    2010-01-01

    The proposed new measurements comprise a Generalised Parton Distributions programme, an unpolarised PDF and FF programme, a transverse momentum dependent PDF programme and a programme for tests of chiral perturbation theory.

  2. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: Teaching Drug Marketers How to Inform Better or Spin Better? Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Doran, Evan

    2016-02-21

    Hyosun Kim's report "Trouble Spots in Online Direct to Consumer Prescription Drug Promotion: A content Analysis of FDA Warning Letters" aims to teach marketers how to avoid breaching current Food and Drug Administration (FDA) guidelines in their online drug promotion. While Kim hopes to minimise the potential for online promotion to misinform consumers and the study is carefully conducted, teaching drug marketers how to avoid the common mistakes in online drug promotion is more likely to make marketers more adept at spinning information than appropriately balancing it. © 2016 by Kerman University of Medical Sciences.

  3. A proposed analytic framework for determining the impact of an antimicrobial resistance intervention.

    Science.gov (United States)

    Grohn, Yrjo T; Carson, Carolee; Lanzas, Cristina; Pullum, Laura; Stanhope, Michael; Volkova, Victoriya

    2017-06-01

    Antimicrobial use (AMU) is increasingly threatened by antimicrobial resistance (AMR). The FDA is implementing risk mitigation measures promoting prudent AMU in food animals. Their evaluation is crucial: the AMU/AMR relationship is complex; a suitable framework to analyze interventions is unavailable. Systems science analysis, depicting variables and their associations, would help integrate mathematics/epidemiology to evaluate the relationship. This would identify informative data and models to evaluate interventions. This National Institute for Mathematical and Biological Synthesis AMR Working Group's report proposes a system framework to address the methodological gap linking livestock AMU and AMR in foodborne bacteria. It could evaluate how AMU (and interventions) impact AMR. We will evaluate pharmacokinetic/dynamic modeling techniques for projecting AMR selection pressure on enteric bacteria. We study two methods to model phenotypic AMR changes in bacteria in the food supply and evolutionary genotypic analyses determining molecular changes in phenotypic AMR. Systems science analysis integrates the methods, showing how resistance in the food supply is explained by AMU and concurrent factors influencing the whole system. This process is updated with data and techniques to improve prediction and inform improvements for AMU/AMR surveillance. Our proposed framework reflects both the AMR system's complexity, and desire for simple, reliable conclusions.

  4. Invasive Candidiasis in Various Patient Populations: Incorporating Non-Culture Diagnostic Tests into Rational Management Strategies

    Science.gov (United States)

    Clancy, Cornelius J.; Shields, Ryan K.; Nguyen, M. Hong

    2016-01-01

    Mortality rates due to invasive candidiasis remain unacceptably high, in part because the poor sensitivity and slow turn-around time of cultures delay the initiation of antifungal treatment. β-d-glucan (Fungitell) and polymerase chain reaction (PCR)-based (T2Candida) assays are FDA-approved adjuncts to cultures for diagnosing invasive candidiasis, but their clinical roles are unclear. We propose a Bayesian framework for interpreting non-culture test results and developing rational patient management strategies, which considers test performance and types of invasive candidiasis that are most common in various patient populations. β-d-glucan sensitivity/specificity for candidemia and intra-abdominal candidiasis is ~80%/80% and ~60%/75%, respectively. In settings with 1%–10% likelihood of candidemia, anticipated β-d-glucan positive and negative predictive values are ~4%–31% and ≥97%, respectively. Corresponding values in settings with 3%–30% likelihood of intra-abdominal candidiasis are ~7%–51% and ~78%–98%. β-d-glucan is predicted to be useful in guiding antifungal treatment for wide ranges of populations at-risk for candidemia (incidence ~5%–40%) or intra-abdominal candidiasis (~7%–20%). Validated PCR-based assays should broaden windows to include populations at lower-risk for candidemia (incidence ≥~2%) and higher-risk for intra-abdominal candidiasis (up to ~40%). In the management of individual patients, non-culture tests may also have value outside of these windows. The proposals we put forth are not definitive treatment guidelines, but rather represent starting points for clinical trial design and debate by the infectious diseases community. The principles presented here will be applicable to other assays as they enter the clinic, and to existing assays as more data become available from different populations. PMID:29376927

  5. Invasive Candidiasis in Various Patient Populations: Incorporating Non-Culture Diagnostic Tests into Rational Management Strategies

    Directory of Open Access Journals (Sweden)

    Cornelius J. Clancy

    2016-02-01

    Full Text Available Mortality rates due to invasive candidiasis remain unacceptably high, in part because the poor sensitivity and slow turn-around time of cultures delay the initiation of antifungal treatment. β-d-glucan (Fungitell and polymerase chain reaction (PCR-based (T2Candida assays are FDA-approved adjuncts to cultures for diagnosing invasive candidiasis, but their clinical roles are unclear. We propose a Bayesian framework for interpreting non-culture test results and developing rational patient management strategies, which considers test performance and types of invasive candidiasis that are most common in various patient populations. β-d-glucan sensitivity/specificity for candidemia and intra-abdominal candidiasis is ~80%/80% and ~60%/75%, respectively. In settings with 1%–10% likelihood of candidemia, anticipated β-d-glucan positive and negative predictive values are ~4%–31% and ≥97%, respectively. Corresponding values in settings with 3%–30% likelihood of intra-abdominal candidiasis are ~7%–51% and ~78%–98%. β-d-glucan is predicted to be useful in guiding antifungal treatment for wide ranges of populations at-risk for candidemia (incidence ~5%–40% or intra-abdominal candidiasis (~7%–20%. Validated PCR-based assays should broaden windows to include populations at lower-risk for candidemia (incidence ≥~2% and higher-risk for intra-abdominal candidiasis (up to ~40%. In the management of individual patients, non-culture tests may also have value outside of these windows. The proposals we put forth are not definitive treatment guidelines, but rather represent starting points for clinical trial design and debate by the infectious diseases community. The principles presented here will be applicable to other assays as they enter the clinic, and to existing assays as more data become available from different populations.

  6. 75 FR 40839 - Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis...

    Science.gov (United States)

    2010-07-14

    ... this total are 850 plants currently identified in FDA's official establishment inventory plus 1,220 very small apple juice manufacturers and 230 very small orange juice manufacturers. The total burden...

  7. 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

  8. Proposal for testing lepton universality in upsilon decays at a B factory running at Υ(3S)

    International Nuclear Information System (INIS)

    Sanchis-Lozano, Miguel-Angel

    2007-01-01

    A proposal is presented for detecting new physics at a B factory running at the Υ(3S) resonance by testing lepton universality to the few percent level in the leptonic decays of the Υ(1S) and Υ(2S) resonances tagged by the dipion in the chain decay: Υ(3S) → π + π - Υ(1S,2S); Υ(1S,2S) → l + l - , l=e,μ,τ. (author)

  9. Ecological evaluation of proposed dredged material from the John F. Baldwin Ship Channel: Phase 3 -- biological testing

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, N.P.; Karle, L.M.; Pinza, M.R.; Mayhew, H.L.; White, P.J.; Gruendell, B.D.; Word, J.Q. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1993-10-01

    The John F. Baldwin Ship Channel is a 28-mile-long portion of the San Francisco Bay to Stockton Ship Channel, the primary shipping lane through San Francisco Bay and Delta. The San Francisco District of the US Army Corps of Engineers (USACE) is responsible for construction of the John F. Baldwin Ship Channel, which is authorized to be deepened to a project depth of {minus}45 ft relative to mean lower low water (MLLW). Approximately 8.5 million cubic yards (mcy) of sediment will be removed from the channel to reach this project depth. The USACE requested Battelle/Marine Sciences Laboratory (MSL) to conduct testing for ocean disposal under the guidelines in Evaluation of Dredged Material Proposed for Ocean Disposal-Testing Manual (EPA/USACE 1991). This testing manual contains a tiered evaluation approach developed specifically for ocean disposal of dredged material at a selected site. In this study, John F. Baldwin Ship Channel sediments were evaluated under the Tier III (biological) testing guidance, which is considered to be highly stringent and protective of the environment. The Tier III guidance for ocean disposal testing requires tests of water column effects, (following dredged material disposal), deposited sediment toxicity, and bioaccumulation of contaminants from deposited sediment (dredged material).

  10. 75 FR 67093 - Iceberg Water Deviating From Identity Standard; Temporary Permit for Market Testing

    Science.gov (United States)

    2010-11-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-P-0517... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a... mass production problems, and assess commercial feasibility. DATES: This permit is effective for 15...

  11. 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.

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

    Science.gov (United States)

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    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. 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. 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. 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.

  13. Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing.

    Science.gov (United States)

    Demarco, Maria; Carter-Pokras, Olivia; Hyun, Noorie; Castle, Philip E; He, Xin; Dallal, Cher M; Chen, Jie; Gage, Julia C; Befano, Brian; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy; Raine-Bennett, Tina R; Wentzensen, Nicolas; Schiffman, Mark

    2018-05-01

    As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity (Becton Dickinson Diagnostics, Sparks, MD), a nine-channel HPV test recently approved by the FDA, by assessing (i) the association of Onclarity types/channels with precancer/cancer; (ii) HPV type/channel agreement between the results of Onclarity and cobas (Roche Molecular Systems, Pleasanton, CA), another FDA-approved test; and (iii) Onclarity typing for all types/channels compared to typing results from a research assay (linear array [LA]; Roche). We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample ( n = 9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2; Qiagen, Germantown, MD). A subset had already been tested by cobas and LA ( n = 1,965). Cervical histopathology was ascertained from electronic health records. Hierarchical Onclarity channels showed a significant linear association with histological severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other 12 types as a pool (sample-weighted kappa value of 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and groups of types identified by LA (kappa values from 0.80 for HPV39/68/35 to 0.97 for HPV16). Onclarity typing results corresponded well to histopathology and to an already validated HPV DNA test and could provide additional clinical typing if such discrimination is determined to be clinically desirable. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  14. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: Teaching Drug Marketers How to Inform Better or Spin Better?; 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)

    Evan Doran

    2016-05-01

    Full Text Available Hyosun Kim’s report “Trouble Spots in Online Direct to Consumer Prescription Drug Promotion: A content Analysis of FDA Warning Letters”aims to teach marketers how to avoid breaching current Food and Drug Administration (FDA guidelines in their online drug promotion. While Kim hopes to minimise the potential for online promotion to misinform consumers and the study is carefully conducted, teaching drug marketers how to avoid the common mistakes in online drug promotion is more likely to make marketers more adept at spinning information than appropriately balancing it.

  15. 76 FR 32362 - Agency Information Collection Activities: Proposed Collection; Reports and Records Under...

    Science.gov (United States)

    2011-06-06

    ... wholesalers and retailers who had to pay otherwise prevailing market prices. FDA is requesting OMB approval... discrepancies and significant losses revealed through the reconciliation report. 21 CFR 203.31(e) Lists of...

  16. Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection

    Science.gov (United States)

    Cross, Robert W.; Boisen, Matthew L.; Millett, Molly M.; Nelson, Diana S.; Oottamasathien, Darin; Hartnett, Jessica N.; Jones, Abigal B.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Bornholdt, Zachary A.; Fusco, Marnie L.; Abelson, Dafna M.; Oda, Shunichiro; Brown, Bethany L.; Pham, Ha; Rowland, Megan M.; Agans, Krystle N.; Geisbert, Joan B.; Heinrich, Megan L.; Kulakosky, Peter C.; Shaffer, Jeffrey G.; Schieffelin, John S.; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M.; Wilson, Russell B.; Saphire, Erica Ollmann; Pitts, Kelly R.; Khan, Sheik Humarr; Grant, Donald S.; Geisbert, Thomas W.; Branco, Luis M.; Garry, Robert F.

    2016-01-01

    Background. Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013–2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. Methods. Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance. Results. The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription–polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 105–9.0 × 108 genomes/mL. Conclusions. The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015. PMID:27587634

  17. A proposed holistic approach to on-chip, off-chip, test, and package interconnections

    Science.gov (United States)

    Bartelink, Dirk J.

    1998-11-01

    recognize—test is also performed using IC's. A system interconnection is proposed using multiple chips fabricated with conventional silicon processes, including MEMS technology. The system resembles an MCM that can be joined without committing to final assembly to perform at-speed testing. 50-Ohm test probes never load the circuit; only intended neighboring chips are ever connected. A `back-plane' chip provides the connection layers for both inter- and intra-chip signals and also serves as the probe card, in analogy with membrane probes now used for single-chip testing. Intra-chip connections, which require complicated connections during test that exactly match the product, are then properly made and all waveforms and loading conditions under test will be identical to those of the product. The major benefit is that all front-end chip technologies can be merged—logic, memory, RF, even passives. ESD protection is required only on external system connections. Manufacturing test information will accurately characterize process faults and thus avoid the Known-Good-Die problem that has slowed the arrival of conventional MCM's.

  18. A proposed structural, risk-informed approach to the periodicity of CANDU-6 nuclear containment integrated leak rate testing

    Energy Technology Data Exchange (ETDEWEB)

    Saliba, N. [McGill Univ., Dept. of Civil Engineering and Applied Mechanics, Montreal, Quebec (Canada); Komljenovic, D. [Hydro-Quebec, Gentilly-2 Nuclear Power Plant, Becancour, Quebec (Canada); Chouinard, L. [McGill Univ., Dept. of Civil Engineering and Applied Mechanics, Montreal, Quebec (Canada); Vaillancourt, R.; Chretien, G. [Hydro-Quebec, Gentilly-2 Nuclear Power Plant, Becancour, Quebec (Canada); Gocevski, V. [Hydro-Quebec Equipements, Montreal, Quebec (Canada)

    2010-07-01

    As ultimate lines of defense against leakage of large amounts of radioactive material to the environment in case of major reactor accidents, containments have been monitored through well designed periodic tests to ensure their proper performance. Regulatory organizations have imposed types and frequencies of containment tests based on highly-conservative deterministic approaches, and judgments of knowledgeable experts. Recent developments in the perception and methods of risk evaluation have been applied to rationalize the leakage-rate testing frequencies while maintaining risks within acceptable levels, preserving the integrity of containments, and respecting the defense-in-depth philosophy. The objective of this paper is to introduce a proposed risk-informed decision making framework on the periodicity of nuclear containment ILRTs for CANDU-6 nuclear power plants based on five main decision criteria, namely: 1) the containment structural integrity; 2) inputs from PSA Level-2; 3) the requirements of deterministic safety analyses and defense-in-depth concepts; 4- the obligations under regulatory and standard requirements; and 5) the return of experience from nuclear containments historic performance. The concepts of dormant reliability and structural fragility will guide the assessment of the containment structural integrity, within the general context of a global containment life cycle management program. This study is oriented towards the requirements of CANDU-6 reactors, in general, and Hydro-Quebec's Gentilly-2 nuclear power plant, in particular. The present article is the first part in a series of papers that will comprehensively detail the proposed research. (author)

  19. A proposed structural, risk-informed approach to the periodicity of CANDU-6 nuclear containment integrated leak rate testing

    International Nuclear Information System (INIS)

    Saliba, N.; Komljenovic, D.; Chouinard, L.; Vaillancourt, R.; Chretien, G.; Gocevski, V.

    2010-01-01

    As ultimate lines of defense against leakage of large amounts of radioactive material to the environment in case of major reactor accidents, containments have been monitored through well designed periodic tests to ensure their proper performance. Regulatory organizations have imposed types and frequencies of containment tests based on highly-conservative deterministic approaches, and judgments of knowledgeable experts. Recent developments in the perception and methods of risk evaluation have been applied to rationalize the leakage-rate testing frequencies while maintaining risks within acceptable levels, preserving the integrity of containments, and respecting the defense-in-depth philosophy. The objective of this paper is to introduce a proposed risk-informed decision making framework on the periodicity of nuclear containment ILRTs for CANDU-6 nuclear power plants based on five main decision criteria, namely: 1) the containment structural integrity; 2) inputs from PSA Level-2; 3) the requirements of deterministic safety analyses and defense-in-depth concepts; 4- the obligations under regulatory and standard requirements; and 5) the return of experience from nuclear containments historic performance. The concepts of dormant reliability and structural fragility will guide the assessment of the containment structural integrity, within the general context of a global containment life cycle management program. This study is oriented towards the requirements of CANDU-6 reactors, in general, and Hydro-Quebec's Gentilly-2 nuclear power plant, in particular. The present article is the first part in a series of papers that will comprehensively detail the proposed research. (author)

  20. Data gaps in toxicity testing of chemicals allowed in food in the United States.

    Science.gov (United States)

    Neltner, Thomas G; Alger, Heather M; Leonard, Jack E; Maffini, Maricel V

    2013-12-01

    In the United States, chemical additives cannot be used in food without an affirmative determination that their use is safe by FDA or additive manufacturer. Feeding toxicology studies designed to estimate the amount of a chemical additive that can be eaten safely provide the most relevant information. We analyze how many chemical additives allowed in human food have feeding toxicology studies in three toxicological information sources including the U.S. Food and Drug Administration's (FDA) database. Less than 38% of FDA-regulated additives have a published feeding study. For chemicals directly added to food, 21.6% have feeding studies necessary to estimate a safe level of exposure and 6.7% have reproductive or developmental toxicity data in FDA's database. A program is needed to fill these significant knowledge gaps by using in vitro and in silico methods complemented with targeted in vivo studies to ensure public health is protected. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. Determination of Natural Levels of Radionuclides in Proposed Mushroom Reference Material (A Proficiency Test Exercise)

    International Nuclear Information System (INIS)

    Waheed, S.; Rahman, A.; Siddique, N.; Ahmad, S.; Zaidi, J.H.

    2006-08-01

    A proficiency test (PT) was organized within the framework of international Atomic Energy Agency (IAEA) project INT/1/054, entitled 'Preparation' of Reference Materials and Organization of Proficiency Test Rounds'. This exercise served to estimate the proficiency of the analytical laboratories from participating countries. This report presents the results of the proficiency test exercise on the proposed Mushroom Reference Material for the determination of natural levels of radionuclides. Laboratories from 6 different countries submitted data on the following three radionuclides: /sup 134/Cs, /sup 137/Cs, /sup 40/K. Results for /sup 134/Cs, 137/sup 137/Cs, and /sup 40/K in the mushroom reference material were reported by three or more participating laboratories and could be subjected to statistical evaluation. The original data of these raionuclides was subjected to a computer program 'Histo Vession 2.1' provided by IAEA. The four outlier tests i.e. Dixon, Grubbs, Skewness and Kurtosis were applied to the data sets. All values for these three radionuclides were accepted by the software. Consensus (overall) mean value, absolute standard deviation, relative standard deviation, standard error, median and range of values for these three radionuclides have been are obtained (at significance level 0.05). the consensus mean values and confidence intervals are given./sup 134/Cs: 4.4 Bq/kg (3.4-5.3 Bq/kg) /sup 137/Cs: 2899 Bq/kg (2740-3058 Bq/kg) /sup 40/K: 1136 Bq/kg (1046-1226 Bq/kg). (author)

  3. OSQAR-CHASE Proposal

    CERN Document Server

    (Pugnat, P; (Sulc, M

    2015-01-01

    For 2015, the OSQAR collaboration will focus on a new proposal for the search of chameleon, a hypothetical scalar particle postulated as a dark energy candidate with an environment-dependant mass. The required experimental set-up has been successfully tested and validated in 2014 at the SM-18 experimental hall. This proposal will focus on the sensitivity that can be reached during the OSQAR chameleon run in 2015 as well as to possible upgrade phases of the experiment for the coming years.

  4. FDA Consumer Nutrition Knowledge Survey. Report II, 1975. A Nationwide Study of Food Shopper's Knowledge, Beliefs, Attitudes and Reported Behavior Regarding Food and Nutrition. Factors Related to Nutrition Labeling.

    Science.gov (United States)

    Abelson, Herbert; And Others

    During 1973, a nationwide study for the Food and Drug Administration (FDA) was conducted which provided information on nutrition knowledge, beliefs about nutrition, and first reactions to nutrition labeling among food shoppers. This initial research provided a baseline measurement of nutrition knowledge and attitudes among consumers, and in 1975…

  5. Towards reporting standards for neuropsychological study results: A proposal to minimize communication errors with standardized qualitative descriptors for normalized test scores.

    Science.gov (United States)

    Schoenberg, Mike R; Rum, Ruba S

    2017-11-01

    Rapid, clear and efficient communication of neuropsychological results is essential to benefit patient care. Errors in communication are a lead cause of medical errors; nevertheless, there remains a lack of consistency in how neuropsychological scores are communicated. A major limitation in the communication of neuropsychological results is the inconsistent use of qualitative descriptors for standardized test scores and the use of vague terminology. PubMed search from 1 Jan 2007 to 1 Aug 2016 to identify guidelines or consensus statements for the description and reporting of qualitative terms to communicate neuropsychological test scores was conducted. The review found the use of confusing and overlapping terms to describe various ranges of percentile standardized test scores. In response, we propose a simplified set of qualitative descriptors for normalized test scores (Q-Simple) as a means to reduce errors in communicating test results. The Q-Simple qualitative terms are: 'very superior', 'superior', 'high average', 'average', 'low average', 'borderline' and 'abnormal/impaired'. A case example illustrates the proposed Q-Simple qualitative classification system to communicate neuropsychological results for neurosurgical planning. The Q-Simple qualitative descriptor system is aimed as a means to improve and standardize communication of standardized neuropsychological test scores. Research are needed to further evaluate neuropsychological communication errors. Conveying the clinical implications of neuropsychological results in a manner that minimizes risk for communication errors is a quintessential component of evidence-based practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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

  7. 75 FR 42094 - Agency Information Collection Activities; Proposed Collection; Comment Request; Designated New...

    Science.gov (United States)

    2010-07-20

    ... the Federal Food, Drug, and Cosmetic Act (the act) to authorize FDA to establish new regulatory..., chickens, turkeys, dogs, and cats) that are needed for diseases that occur in only a small number of...

  8. 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.

  9. 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.

  10. Intertechnology Corporation proposed test and evaluation plan, commercial buildings. National Solar Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-09-01

    This report has three major parts. The first of these derives the requirements for the Test and Evaluation plan from the System Level Plan which is summarized in Section II. The second part contains the proposed plan to fill these requirements and includes hardware and software recommendations as well as procedures and management considerations. Primary emphasis has been given to the remote site because this is the area in which the commercial part of the demonstration is most unique. Finally, some pre-demonstration activities are described. The pilot program is intended to resolve a number of issues which arose in the course of the T and E plan. These relate to choice of scan frequencies, compression algorithms, etc. It is also intended to confirm performance and cost effectiveness of the site data collection package. The base line measurements of attitudes, etc. provide a reference mark against which one can measure the non-technical effectiveness of the demonstration program. (WDM)

  11. 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.

  12. Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Organophosphate Test System. Final order.

    Science.gov (United States)

    2017-10-18

    The Food and Drug Administration (FDA or we) is classifying the organophosphate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the organophosphate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  13. Medical Devices; Hematology and Pathology Devices; Classification of a Cervical Intraepithelial Neoplasia Test System. Final order.

    Science.gov (United States)

    2018-01-03

    The Food and Drug Administration (FDA or we) is classifying the cervical intraepithelial neoplasia (CIN) test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the CIN test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  14. Creep-fatigue evaluation method for weld joint of Mod.9Cr-1Mo steel Part II: Plate bending test and proposal of a simplified evaluation method

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Masanori, E-mail: ando.masanori@jaea.go.jp; Takaya, Shigeru, E-mail: takaya.shigeru@jaea.go.jp

    2016-12-15

    Highlights: • Creep-fatigue evaluation method for weld joint of Mod.9Cr-1Mo steel is proposed. • A simplified evaluation method is also proposed for the codification. • Both proposed evaluation method was validated by the plate bending test. • For codification, the local stress and strain behavior was analyzed. - Abstract: In the present study, to develop an evaluation procedure and design rules for Mod.9Cr-1Mo steel weld joints, a method for evaluating the creep-fatigue life of Mod.9Cr-1Mo steel weld joints was proposed based on finite element analysis (FEA) and a series of cyclic plate bending tests of longitudinal and horizontal seamed plates. The strain concentration and redistribution behaviors were evaluated and the failure cycles were estimated using FEA by considering the test conditions and metallurgical discontinuities in the weld joints. Inelastic FEA models consisting of the base metal, heat-affected zone and weld metal were employed to estimate the elastic follow-up behavior caused by the metallurgical discontinuities. The elastic follow-up factors determined by comparing the elastic and inelastic FEA results were determined to be less than 1.5. Based on the estimated elastic follow-up factors obtained via inelastic FEA, a simplified technique using elastic FEA was proposed for evaluating the creep-fatigue life in Mod.9Cr-1Mo steel weld joints. The creep-fatigue life obtained using the plate bending test was compared to those estimated from the results of inelastic FEA and by a simplified evaluation method.

  15. Creep-fatigue evaluation method for weld joint of Mod.9Cr-1Mo steel Part II: Plate bending test and proposal of a simplified evaluation method

    International Nuclear Information System (INIS)

    Ando, Masanori; Takaya, Shigeru

    2016-01-01

    Highlights: • Creep-fatigue evaluation method for weld joint of Mod.9Cr-1Mo steel is proposed. • A simplified evaluation method is also proposed for the codification. • Both proposed evaluation method was validated by the plate bending test. • For codification, the local stress and strain behavior was analyzed. - Abstract: In the present study, to develop an evaluation procedure and design rules for Mod.9Cr-1Mo steel weld joints, a method for evaluating the creep-fatigue life of Mod.9Cr-1Mo steel weld joints was proposed based on finite element analysis (FEA) and a series of cyclic plate bending tests of longitudinal and horizontal seamed plates. The strain concentration and redistribution behaviors were evaluated and the failure cycles were estimated using FEA by considering the test conditions and metallurgical discontinuities in the weld joints. Inelastic FEA models consisting of the base metal, heat-affected zone and weld metal were employed to estimate the elastic follow-up behavior caused by the metallurgical discontinuities. The elastic follow-up factors determined by comparing the elastic and inelastic FEA results were determined to be less than 1.5. Based on the estimated elastic follow-up factors obtained via inelastic FEA, a simplified technique using elastic FEA was proposed for evaluating the creep-fatigue life in Mod.9Cr-1Mo steel weld joints. The creep-fatigue life obtained using the plate bending test was compared to those estimated from the results of inelastic FEA and by a simplified evaluation method.

  16. Pharmacogenetic testing through the direct-to-consumer genetic testing company 23andMe.

    Science.gov (United States)

    Lu, Mengfei; Lewis, Cathryn M; Traylor, Matthew

    2017-06-19

    Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity. A wider literature search was performed to provide a fuller assessment of the pharmacogenetic test and variants were matched to FDA recommendations. Additional evidence from CPIC guidelines, PharmGKB, and Dutch Pharmacogenetics Working Group was reviewed to determine current clinical practice. The value of the tests across ethnic groups was determined, including information on linkage disequilibrium between the tested SNP and causal pharmacogenetic variant, where relevant. 23andMe offers 12 pharmacogenetic tests to their UK customers, some of which are in standard clinical practice, and others which are less widely applied. The clinical validity and clinical utility varies extensively between tests. The variants tested are likely to have different degrees of sensitivity due to different risk allele frequencies and linkage disequilibrium patterns across populations. The clinical relevance depends on the ethnicity of the individual and variability of pharmacogenetic markers. Further research is required to determine causal variants and provide more complete assessment of drug response and side effects. 23andMe reports provide some useful pharmacogenetics information, mirroring clinical tests that are in standard use. Other tests are unspecific, providing limited guidance and may not be useful for patients without professional interpretation. Nevertheless, DTC companies like 23andMe act as a powerful

  17. 78 FR 38992 - Agency Information Collection Activities; Proposed Collection; Comment Request; Reports of...

    Science.gov (United States)

    2013-06-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0723... site will provide the following information: Introduction Tracking information Contact information [cir... [cir] Domestic consignee information [cir] Foreign consignee information [cir] Communication...

  18. 75 FR 42093 - Agency Information Collection Activities; Proposed Collection; Comment Request; Information...

    Science.gov (United States)

    2010-07-20

    ... Control Act amended the Federal Food, Drug, and Cosmetic Act by adding a new chapter granting FDA important new authority to regulate the manufacture, marketing, and distribution of tobacco products to... strategies for each brand or subbrand of menthol cigarettes, including strategies targeted to particular...

  19. 76 FR 48167 - Agency Information Collection Activities; Proposed Collection; Comment Request; Blood...

    Science.gov (United States)

    2011-08-08

    ... requirements in the Agency's regulations and Form FDA 2830. DATES: Submit either electronic or written comments on the collection of information by October 7, 2011. ADDRESSES: Submit electronic comments on the... plasma donor centers, blood banks, certain transfusion services, other blood product manufacturers, and...

  20. 77 FR 18250 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental...

    Science.gov (United States)

    2012-03-27

    ... impact on consumer perceptions, attitudes, and behavior with respect to smoking. On June 22, 2011, FDA...: (1) Measure consumer attitudes, beliefs, and intended behaviors related to cigarette smoking in... of the Family Smoking Prevention and Tobacco Control Act (the Tobacco Control Act). DATES: Submit...

  1. Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection.

    Science.gov (United States)

    Cross, Robert W; Boisen, Matthew L; Millett, Molly M; Nelson, Diana S; Oottamasathien, Darin; Hartnett, Jessica N; Jones, Abigal B; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Bornholdt, Zachary A; Fusco, Marnie L; Abelson, Dafna M; Oda, Shunichiro; Brown, Bethany L; Pham, Ha; Rowland, Megan M; Agans, Krystle N; Geisbert, Joan B; Heinrich, Megan L; Kulakosky, Peter C; Shaffer, Jeffrey G; Schieffelin, John S; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M; Wilson, Russell B; Saphire, Erica Ollmann; Pitts, Kelly R; Khan, Sheik Humarr; Grant, Donald S; Geisbert, Thomas W; Branco, Luis M; Garry, Robert F

    2016-10-15

     Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases.  Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance.  The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription-polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 10 5 -9.0 × 10 8 genomes/mL.  The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. 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.

  3. 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.

  4. 75 FR 33624 - Agency Information Collection Activities; Proposed Collection; Comment Request; Submission of...

    Science.gov (United States)

    2010-06-14

    ... the additive in or on food or that may be present in food as a result of its use in articles that... Food Additive Safety in the Center for Food Safety and Applied Nutrition using Form FDA 3503 for FAP...

  5. 75 FR 61490 - Agency Information Collection Activities; Proposed Collection; Comment Request; National Consumer...

    Science.gov (United States)

    2010-10-05

    ... communications (advertising and labeling) about prescription drugs, biologics, and restricted medical devices, and a subset of communications (omitting advertising) about nonprescription drugs and other medical... of more effective risk communication strategies and messages. The surveys will provide FDA insight as...

  6. 76 FR 28689 - Microbiology Devices; Classification of In Vitro Diagnostic Device for Bacillus Species Detection

    Science.gov (United States)

    2011-05-18

    .... FDA-2011-N-0103] Microbiology Devices; Classification of In Vitro Diagnostic Device for Bacillus... of the Microbiology Devices Advisory Panel (the Panel). In addition, the proposed rule would... in the Federal Register. 1. Transcript of the FDA Microbiology Devices Panel meeting, March 7, 2002...

  7. 77 FR 36984 - International Standard-Setting Activities

    Science.gov (United States)

    2012-06-20

    .../FDA. U.S. Participation: Yes. Cocoa Products and Chocolate Responsible Agency: HHS/FDA. U.S... (cattle liver) at Step 5/8. Proposed draft Sampling Plans for Residue Control for Aquatic Animal Products and Derived Edible Products of Aquatic Origin at Step 5/8. [[Page 36987

  8. 77 FR 4329 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental...

    Science.gov (United States)

    2012-01-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0020... reasonably determines that a disclaimer would not eliminate the potential deception (Pearson v. Shalala, 164... the Labeling of Conventional Human Foods and Human Dietary Supplements, 2003, available at http://www...

  9. 78 FR 33846 - Agency Information Collection Activities; Proposed Collection; Comment Request; Biological...

    Science.gov (United States)

    2013-06-05

    ..., and Forms FDA 3486 and 3486A. DATES: Submit electronic or written comments on the collection of information by August 5, 2013. ADDRESSES: Submit electronic comments on the collection of information to: http... Source Plasma, unlicensed registered blood establishments, and transfusion services, who had control over...

  10. 78 FR 18983 - Proposed Data Collections Submitted for Public Comment and Recommendations

    Science.gov (United States)

    2013-03-28

    ... Calculate Workload for FDA-Approved Semi-Automated Gynecologic Cytology Screening Devices. In this alert, it... cytotechnologist productivity should not exceed 70 slides and that an individual's screening time should not exceed... instruments is appropriate and to discourage the use of regulatory maximum workload limits as productivity...

  11. 77 FR 56847 - Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic...

    Science.gov (United States)

    2012-09-14

    ... Number 0910-0645)--Revision The SRP (formerly referred to as the MedWatch\\Plus\\ Portal and Rational Questionnaire) and the ESG are the Agency's electronic systems for collecting, submitting, and processing... ESG, approved under OMB control number 0910-0645. III. The FDA Safety Reporting Portal Rational...

  12. 75 FR 12552 - Agency Information Collection Activities; Proposed Collection; Comment Request; Requirements...

    Science.gov (United States)

    2010-03-16

    ... Budget (OMB) for each collection of information they conduct or sponsor. ``Collection of information'' is... advertising and packaging. FDA is required to review each plan submitted and approve the plan if it provides..., involving multiple brands, multiple brand varieties, and multiple forms of both packaging and advertising...

  13. 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.

  14. Analytical Performance Requirements for Systems for Self-Monitoring of Blood Glucose With Focus on System Accuracy: Relevant Differences Among ISO 15197:2003, ISO 15197:2013, and Current FDA Recommendations.

    Science.gov (United States)

    Freckmann, Guido; Schmid, Christina; Baumstark, Annette; Rutschmann, Malte; Haug, Cornelia; Heinemann, Lutz

    2015-07-01

    In the European Union (EU), the ISO (International Organization for Standardization) 15197 standard is applicable for the evaluation of systems for self-monitoring of blood glucose (SMBG) before the market approval. In 2013, a revised version of this standard was published. Relevant revisions in the analytical performance requirements are the inclusion of the evaluation of influence quantities, for example, hematocrit, and some changes in the testing procedures for measurement precision and system accuracy evaluation, for example, number of test strip lots. Regarding system accuracy evaluation, the most important change is the inclusion of more stringent accuracy criteria. In 2014, the Food and Drug Administration (FDA) in the United States published their own guidance document for the premarket evaluation of SMBG systems with even more stringent system accuracy criteria than stipulated by ISO 15197:2013. The establishment of strict accuracy criteria applicable for the premarket evaluation is a possible approach to further improve the measurement quality of SMBG systems. However, the system accuracy testing procedure is quite complex, and some critical aspects, for example, systematic measurement difference between the reference measurement procedure and a higher-order procedure, may potentially limit the apparent accuracy of a given system. Therefore, the implementation of a harmonized reference measurement procedure for which traceability to standards of higher order is verified through an unbroken, documented chain of calibrations is desirable. In addition, the establishment of regular and standardized post-marketing evaluations of distributed test strip lots should be considered as an approach toward an improved measurement quality of available SMBG systems. © 2015 Diabetes Technology Society.

  15. Comparing perceived effectiveness of FDA-proposed cigarette packaging graphic health warnings between sexual and gender minorities and heterosexual adults.

    Science.gov (United States)

    Tan, Andy S L; Bigman, Cabral A; Nagler, Rebekah H; Minsky, Sara; Viswanath, Kasisomayajula

    2017-10-01

    In 2012, the U.S. Food and Drug Administration proposed nine graphic health warnings (GHWs) on cigarette packaging that were rated equally effective across racial/ethnic, education, or income groups of adult smokers. However, data on GHW effectiveness among sexual and gender minority (SGM) adults, who have higher smoking prevalence, are currently lacking. This study analyzed whether perceived effectiveness of GHWs differed by gender and sexual orientation. Data came from a randomized experiment among 1,200 adults with an oversample from low socioeconomic status groups, conducted between 2013 and 2014 in three Massachusetts communities. Participants viewed and rated the effectiveness of nine GHWs. Mixed effects regression models predicted perceived effectiveness with gender and sexual orientation, adjusting for repeated measurements, GHWs viewed, age, race, ethnicity, smoking status, and health status. Female heterosexuals rated GHWs as more effective than male heterosexual, lesbian, and transgender and other gender respondents. There was no significant difference between female and male heterosexuals versus gay, male bisexual, or female bisexual respondents. Differences by gender and sexual orientation were consistent across all nine GHWs. Significant correlates of higher perceived effectiveness included certain GHWs, older age, being African-American (vs white), being Hispanic (vs non-Hispanic), having less than high school education (vs associate degree or higher), and being current smokers (vs non-smokers). Perceived effectiveness of GHWs was lower in certain SGM groups. We recommend further studies to understand the underlying mechanisms for these findings and investments in research and policy to communicate anti-smoking messages more effectively to SGM populations.

  16. Proposed tokamak poloidal field system development program

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, J.D.; Vogel, H.F.; Warren, R.W.; Weldon, D.M.

    1977-05-01

    A program is proposed to develop poloidal field components for TNS and EPR size tokamak devices and to test these components in realistic circuits. Emphasis is placed upon the development of the most difficult component, the superconducting ohmic-heating coil. Switches must also be developed for testing the coils, and this switching technology is to be extended to meet the requirements for the large scale tokamaks. Test facilities are discussed; power supplies, including a homopolar to drive the coils, are considered; and poloidal field systems studies are proposed.

  17. 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.

  18. 75 FR 40840 - Agency Information Collection Activities; Proposed Collection; Comment Request; Current Good...

    Science.gov (United States)

    2010-07-14

    ... labeling; (10) master manufacturing and batch production; (11) laboratory operations; (12) manufacturing... FDA's regulations in part 111 provide the foundation for the planning, control, and improvement...) water used that may become a component of the dietary supplement; (7) production and process controls...

  19. An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

    Science.gov (United States)

    Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

    2011-06-01

    Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

  20. 76 FR 41434 - Removal of Certain Requirements Related to the Prescription Drug Marketing Act; Opportunity for...

    Science.gov (United States)

    2011-07-14

    .... FDA-2011-N-0446] Removal of Certain Requirements Related to the Prescription Drug Marketing Act... Food and Drug Administration (FDA) is proposing to remove a section of the Prescription Drug Marketing... prior sale, purchase, or trade of such drug,'' starting with the manufacturer, and that the identifying...

  1. Effects of hydroxyl-functionalization and sub-Tg thermal annealing on high pressure pure- and mixed-gas CO2/CH4 separation by polyimide membranes based on 6FDA and triptycene-containing dianhydrides

    KAUST Repository

    Swaidan, Raja; Ghanem, Bader; Litwiller, Eric; Pinnau, Ingo

    2015-01-01

    -structure engaged in inter-chain charge transfer complexes (CTCs), similar to that of low-free-volume 6FDA-APAF polyimide. The isosteric heat of adsorption of CO2 as well as CO2/CH4 solubility selectivities varied negligibly upon replacement of OH with CH3 but CTC

  2. Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database.

    Science.gov (United States)

    Perlman, A; Heyman, S N; Matok, I; Stokar, J; Muszkat, M; Szalat, A

    2017-12-01

    Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. ARF cases were identified using a structured medical query. Medications were identified using both brand and generic names. During the period evaluated, 18,915 reports (out of a total of 3,832,015 registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as the "primary" or "secondary" cause of the adverse event in 96.8% of these cases. The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p SGLT2-inhibitors was significantly greater than the proportion of ARF among cases with T2DM without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p SGLT2-inhibitors, canagliflozin was associated with a higher proportion of reports of renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8% respectively, p SGLT2-inhibitors are associated with an increase in the proportion of reports of ARF compared to other medications. SGLT2-inhibitor agents may differ from one another in their respective risk for ARF. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  3. 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.

  4. Time-Resolved Particle Image Velocimetry Measurements with Wall Shear Stress and Uncertainty Quantification for the FDA Nozzle Model.

    Science.gov (United States)

    Raben, Jaime S; Hariharan, Prasanna; Robinson, Ronald; Malinauskas, Richard; Vlachos, Pavlos P

    2016-03-01

    We present advanced particle image velocimetry (PIV) processing, post-processing, and uncertainty estimation techniques to support the validation of computational fluid dynamics analyses of medical devices. This work is an extension of a previous FDA-sponsored multi-laboratory study, which used a medical device mimicking geometry referred to as the FDA benchmark nozzle model. Experimental measurements were performed using time-resolved PIV at five overlapping regions of the model for Reynolds numbers in the nozzle throat of 500, 2000, 5000, and 8000. Images included a twofold increase in spatial resolution in comparison to the previous study. Data was processed using ensemble correlation, dynamic range enhancement, and phase correlations to increase signal-to-noise ratios and measurement accuracy, and to resolve flow regions with large velocity ranges and gradients, which is typical of many blood-contacting medical devices. Parameters relevant to device safety, including shear stress at the wall and in bulk flow, were computed using radial basis functions. In addition, in-field spatially resolved pressure distributions, Reynolds stresses, and energy dissipation rates were computed from PIV measurements. Velocity measurement uncertainty was estimated directly from the PIV correlation plane, and uncertainty analysis for wall shear stress at each measurement location was performed using a Monte Carlo model. Local velocity uncertainty varied greatly and depended largely on local conditions such as particle seeding, velocity gradients, and particle displacements. Uncertainty in low velocity regions in the sudden expansion section of the nozzle was greatly reduced by over an order of magnitude when dynamic range enhancement was applied. Wall shear stress uncertainty was dominated by uncertainty contributions from velocity estimations, which were shown to account for 90-99% of the total uncertainty. This study provides advancements in the PIV processing methodologies over

  5. 76 FR 38184 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall...

    Science.gov (United States)

    2011-06-29

    ... 2008 to 2010. The resulting number of total recalls (9,303) and terminations (2,858) from this database... per Total annual burden per Total hours respondents respondent responses response Recall strategy (Sec...)......... Termination of a recall (Sec. 953 1 953 10 9,530 7.55(b)) Total 443,820 \\1\\ There are no capital costs or...

  6. Estimating the health and economic effects of the proposed US Food and Drug Administration voluntary sodium reformulation: Microsimulation cost-effectiveness analysis.

    Science.gov (United States)

    Pearson-Stuttard, Jonathan; Kypridemos, Chris; Collins, Brendan; Mozaffarian, Dariush; Huang, Yue; Bandosz, Piotr; Capewell, Simon; Whitsel, Laurie; Wilde, Parke; O'Flaherty, Martin; Micha, Renata

    2018-04-01

    Sodium consumption is a modifiable risk factor for higher blood pressure (BP) and cardiovascular disease (CVD). The US Food and Drug Administration (FDA) has proposed voluntary sodium reduction goals targeting processed and commercially prepared foods. We aimed to quantify the potential health and economic impact of this policy. We used a microsimulation approach of a close-to-reality synthetic population (US IMPACT Food Policy Model) to estimate CVD deaths and cases prevented or postponed, quality-adjusted life years (QALYs), and cost-effectiveness from 2017 to 2036 of 3 scenarios: (1) optimal, 100% compliance with 10-year reformulation targets; (2) modest, 50% compliance with 10-year reformulation targets; and (3) pessimistic, 100% compliance with 2-year reformulation targets, but with no further progress. We used the National Health and Nutrition Examination Survey and high-quality meta-analyses to inform model inputs. Costs included government costs to administer and monitor the policy, industry reformulation costs, and CVD-related healthcare, productivity, and informal care costs. Between 2017 and 2036, the optimal reformulation scenario achieving the FDA sodium reduction targets could prevent approximately 450,000 CVD cases (95% uncertainty interval: 240,000 to 740,000), gain approximately 2.1 million discounted QALYs (1.7 million to 2.4 million), and produce discounted cost savings (health savings minus policy costs) of approximately $41 billion ($14 billion to $81 billion). In the modest and pessimistic scenarios, health gains would be 1.1 million and 0.7 million QALYS, with savings of $19 billion and $12 billion, respectively. All the scenarios were estimated with more than 80% probability to be cost-effective (incremental cost/QALY cost-saving by 2031. Limitations include evaluating only diseases mediated through BP, while decreasing sodium consumption could have beneficial effects upon other health burdens such as gastric cancer. Further, the effect

  7. Modification of the BAX System PCR assay for detecting Salmonella in beef, produce, and soy protein isolate. Performance Tested Method 100201.

    Science.gov (United States)

    Peng, Linda X; Wallace, Morgan; Andaloro, Bridget; Fallon, Dawn; Fleck, Lois; Delduco, Dan; Tice, George

    2011-01-01

    The BAX System PCR assay for Salmonella detection in foods was previously validated as AOAC Research Institute (RI) Performance Tested Method (PTM) 100201. New studies were conducted on beef and produce using the same media and protocol currently approved for the BAX System PCR assay for E. coli O157:H7 multiplex (MP). Additionally, soy protein isolate was tested for matrix extension using the U.S. Food and Drug Administration-Bacteriological Analytical Manual (FDA-BAM) enrichment protocols. The studies compared the BAX System method to the U.S. Department of Agriculture culture method for detecting Salmonella in beef and the FDA-BAM culture method for detecting Salmonella in produce and soy protein isolate. Method comparison studies on low-level inoculates showed that the BAX System assay for Salmonella performed as well as or better than the reference method for detecting Salmonella in beef and produce in 8-24 h enrichment when the BAX System E. coli O157:H7 MP media was used, and soy protein isolate in 20 h enrichment with lactose broth followed by 3 h regrowth in brain heart infusion broth. An inclusivity panel of 104 Salmonella strains with diverse serotypes was tested by the BAX System using the proprietary BAX System media and returned all positive results. Ruggedness factors involved in the enrichment phase were also evaluated by testing outside the specified parameters, and none of the factors examined affected the performance of the assay.

  8. 76 FR 65730 - Agency Information Collection Activities; Proposed Collection; Comment Request; Registration of...

    Science.gov (United States)

    2011-10-24

    ...-date information is critical to conducting these activities with efficiency and effectiveness. Under... product is not subject to marketing or licensing approval requirements; and a list of certain drugs or.../DataStandards/StructuredProductLabeling/ default.htm); Obtaining the digital certificate used with FDA...

  9. 75 FR 36092 - Agency Information Collection Activities; Proposed Collection; Comment Request; Medical Devices...

    Science.gov (United States)

    2010-06-24

    ... Good Manufacturing Practice Quality System Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing an opportunity for public... existing collection of information, and to allow 60 days for public comment in response to the notice. This...

  10. 78 FR 37548 - Agency Information Collection Activities: Proposed Collection; Comment Request; Guidance for...

    Science.gov (United States)

    2013-06-21

    ... Planning for the Effects of High Absenteeism To Ensure Availability of Medically Necessary Drug Products... planning for the effects of high absenteeism to ensure availability of medically necessary drug products... performance of FDA's functions, including whether the information will have practical utility; (2) the...

  11. 76 FR 14405 - Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for...

    Science.gov (United States)

    2011-03-16

    ... cooperative manufacturing arrangements for licensed biologics. DATES: Submit either electronic or written... Public Health Service Act (42 U.S.C. 262). The guidance addresses several types of manufacturing... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No.FDA-2011-N-0085...

  12. Beyond C, H, O, and N! Analysis of the elemental composition of U.S. FDA approved drug architectures.

    Science.gov (United States)

    Smith, Brandon R; Eastman, Candice M; Njardarson, Jon T

    2014-12-11

    The diversity of elements among U.S. Food and Drug Administration (FDA) approved pharmaceuticals is analyzed and reported, with a focus on atoms other than carbon, hydrogen, oxygen, and nitrogen. Our analysis reveals that sulfur, chlorine, fluorine, and phosphorous represent about 90% of elemental substitutions, with sulfur being the fifth most used element followed closely by chlorine, then fluorine and finally phosphorous in the eighth place. The remaining 10% of substitutions are represented by 16 other elements of which bromine, iodine, and iron occur most frequently. The most detailed parts of our analysis are focused on chlorinated drugs as a function of approval date, disease condition, chlorine attachment, and structure. To better aid our chlorine drug analyses, a new poster showcasing the structures of chlorinated pharmaceuticals was created specifically for this study. Phosphorus, bromine, and iodine containing drugs are analyzed closely as well, followed by a discussion about other elements.

  13. Comment on "Proposal of a critical test of the Navier-Stokes-Fourier paradigm for compressible fluid continua".

    Science.gov (United States)

    Felderhof, B U

    2013-08-01

    Recently, a critical test of the Navier-Stokes-Fourier equations for compressible fluid continua was proposed [H. Brenner, Phys. Rev. E 87, 013014 (2013)]. It was shown that the equations of bivelocity hydrodynamics imply that a compressible fluid in an isolated rotating circular cylinder attains a nonequilibrium steady state with a nonuniform temperature increasing radially with distance from the axis. We demonstrate that statistical mechanical arguments, involving Hamiltonian dynamics and ergodicity due to irregularity of the wall, lead instead to a thermal equilibrium state with uniform temperature. This is the situation to be expected in experiment.

  14. Risk mitigation for children exposed to drugs during gestation: A critical role for animal preclinical behavioral testing.

    Science.gov (United States)

    Zucker, Irving

    2017-06-01

    Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, analgesic, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital and acetaminophen. Rodent data helpful in identifying and predicting adverse effects of prenatal drug exposure in children were first generated many years after drugs were FDA-approved and administered to pregnant women. I recommend that enhanced behavioral testing of rodent offspring exposed to drugs prenatally should begin during preclinical drug evaluation and continue during Phase I clinical trials, with findings communicated to physicians and patients in drug labels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  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”

    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.

  16. Flight Tests of a 0.13-Scale Model of the Convair XFY-1 Vertically Rising Airplane in a Setup Simulating that Proposed for Captive-Flight Tests in a Hangar, TED No. NACA DE 368

    Science.gov (United States)

    Lovell, Powell M., Jr.

    1953-01-01

    An experimental investigation has been conducted to determine the dynamic stability and control characteristics of a 0.13-scale free-flight model of the Convair XFY-1 airplane in test setups representing the setup proposed for use in the first flight tests of the full-scale airplane in the Moffett Field airship hangar. The investigation was conducted in two parts: first, tests with the model flying freely in an enclosure simulating the hangar, and second, tests with the model partially restrained by an overhead line attached to the propeller spinner and ground lines attached to the wing and tail tips. The results of the tests indicated that the airplane can be flown without difficulty in the Moffett Field airship hangar if it does not approach too close to the hangar walls. If it does approach too close to the walls, the recirculation of the propeller slipstream might cause sudden trim changes which would make smooth flight difficult for the pilot to accomplish. It appeared that the tethering system proposed by Convair could provide generally satisfactory restraint of large-amplitude motions caused by control failure or pilot error without interfering with normal flying or causing any serious instability or violent jerking motions as the tethering lines restrained the model.

  17. 77 FR 50701 - Gastrointestinal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-08-22

    ... always check the Agency's Web site at http://www.fda.gov/AdvisoryCommittees/default.htm and scroll down... (teduglutide) for subcutaneous injection, by NPS Pharmaceuticals, Inc, for the proposed indication of treatment of adult patients with short bowel syndrome. FDA intends to make background material available to the...

  18. 77 FR 36279 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Science.gov (United States)

    2012-06-18

    ... Biologics Price Competition and Innovation Act of 2009 (BPCI Act) that amends the Public Health Service Act... Service Act as a ``351(k) application''. Under FDA's proposed biosimilar biological product user fee... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0194...

  19. Proposed limiting values for performance criteria in acceptance testing of diagnostic X-ray equipment in the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Baeuml, A.

    1989-01-01

    In the Federal Republic of Germany a new X-ray ordinance came into force in 1988 containing a specific paragraph on quality assurance for all medical X-ray units stipulating acceptance tests, regular checks and supervision by medical bodies and the competent authorities. Acceptance testing is to be performed by engineers from equipment suppliers of manufacturers in new and existing installations. It is expected that the service engineers will adjust the equipment in such a way as to obtain optimal performance before measurements are made, the results of which are to be stated in a certificate describing quality status of the equipment. A working group has developed guidelines for these acceptance tests. Items to be measured are reported and proposed limiting values and their tolerances are discussed. (author)

  20. Proposed limiting values for performance criteria in acceptance testing of diagnostic X-ray equipment in the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Baeuml, A.

    1989-01-01

    In the Federal Republic of Germany a new X-ray ordinance came into force in 1988 containing a specific paragraph on quality assurance for all medical X-ray units stipulating acceptance tests, regular checks and supervision by medical bodies and the competent authorities. Acceptance testing is to be performed by engineers from the equipment suppliers or manufacturers in new and also existing installations. It is expected that the service engineers will adjust the equipment in such a way as to obtain optimal performance before measurements are made, the results of which are to be stated in a certificate describing the quality status of the equipment. A working group has developed guidelines for these acceptance tests. The items to be measured are reported and the proposed limiting values and their tolerances are discussed. (author)