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Sample records for bioequivalence requirements procedures

  1. 21 CFR 320.21 - Requirements for submission of bioavailability and bioequivalence data.

    Science.gov (United States)

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS... that there may be bioequivalence issues or concerns with the product, FDA may require that the... special patient population, e.g., infants, if clinical studies are required to support the new or...

  2. 21 CFR 320.30 - Inquiries regarding bioavailability and bioequivalence requirements and review of protocols by...

    Science.gov (United States)

    2010-04-01

    ... appropriate. (3) The proposed chemical and statistical analytical methods are adequate. (c)(1) General... and Drug Administration, Center for Drug Evaluation and Research, Office of Clinical Pharmacology, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002. (2) General inquiries relating to bioequivalence...

  3. 11 CFR 200.2 - Procedural requirements.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Procedural requirements. 200.2 Section 200.2 Federal Elections FEDERAL ELECTION COMMISSION ADMINISTRATIVE REGULATIONS PETITIONS FOR RULEMAKING § 200.2 Procedural requirements. (a) Any interested person may file with the Commission a written petition for the...

  4. 12 CFR 574.6 - Procedural requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Procedural requirements. 574.6 Section 574.6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY ACQUISITION OF CONTROL OF SAVINGS ASSOCIATIONS § 574.6 Procedural requirements. (a) Form of application or notice. An application...

  5. Changing paradigms in bioequivalence trials submitted to the EMA for evaluation - A clinical and regulatory perspective.

    Science.gov (United States)

    Refalo, Nathaniel; Chetcuti, Daniel; Tanti, Amy; Serracino-Inglott, Anthony; Borg, John Joseph

    2017-02-01

    The selection of a robust bioequivalence (BE) study designs for registering a generic product remains still a hard task. This task is still challenging despite the fact that generic products are much needed by health care providers in economical terms. Thus, BE study designs could be a means to allow companies to reduce costs and reach the market earlier. We therefore investigated whether different approaches in various products assessed by the European Medicines Agency during the approval phase resulted in a reduction in resources required to show bioequivalence for different medicinal products. European Public Assessment Reports (EPARs) for off-patent medicinal products authorised within the European Union (EU) through the centralised procedure during the period 2007-2015 were retrieved and reviewed to identify the clinical studies that resulted in fewer number of subjects, the number of centres or trial duration versus the two-period crossover design. 7 studies out of 108 were considered as having benefitted from having a different design. Differences noted included having a different dose allocation scheme, having a different number of dosing periods, having a different number of treatment arms, and having one study evaluating different strengths. Benefits noted included a decrease in the number of subjects and centres required, decreases in study duration and a reduced number of studies required to demonstrate bioequivalence. Bioequivalence studies can be designed in a specific manner to require fewer resources to carry out. Fewer resources required to register a medicinal product, could impart an advantage to companies (such as to be first on the market) or could even translate to making medicines more accessible (such as cheaper) to patients.

  6. Organizational aspects of conducting of bioequivalence study

    Directory of Open Access Journals (Sweden)

    Khokhlov A.L.

    2014-03-01

    Full Text Available Aim: to evaluate the organizational aspects of conducting bioequivalence study in Russia on the example of one of the clinical centers, Yaroslavl. Material and methods. On the basis of the Municipal Autonomous institution of health care of the Yaroslavl region Clinical hospital №2 (CH, clinical base of the Department of clinical pharmacology of YSMA was held 93 bioequivalence studies and pharmacokinetics in the period from 2011 to 2014, of which 15 studies of foreign sponsors and 78 of domestic producers. Result.: The studies involved 48 volunteers of both sexes from the database of clinical center CH №2. There were 698 females (48.6% and 739 males (51.4%. The average age of the volunteers was 26,37 years. In each study there were from 18 to 103 volunteers, depending on the design of the research Protocol. At the same time Russian studies ranged about 18-24 volunteers, about 30-103 volunteers abroad. The number of doubles in domestic studies ranged from 2 to 6 persons, and foreign — from 6 to 12 people. 10-15% from the whole number of subjects were not included into the study. Conclusion. In Russia bioequivalence of medicines for more than ten years is the main requirement of medico-biological control generic drugs. Regardless of the manufacturer to the generic drugs are exactly the same as the original drugs, must meet the following requirements: quality efficiency and safety. In connection with the increase in recent years of bioequivalence studies of medicines, require close monitoring of the quality of these studies on the territory of the Russian Federation.

  7. [Bioequivalence studies of pharmaceutical preparations].

    Science.gov (United States)

    Vetchý, D; Frýbortová, K; Rabisková, M; Danecková, H

    2007-01-01

    Bioequivalence studies are very important for the development of a pharmaceutical preparation in the pharmaceutical industry. Their rationale is the monitoring of pharmacokinetic and pharmacodynamic parameters after the administration of tested drugs. The target of such study is to evaluate the therapeutic compatibility of tested drugs (pharmaceutical equivalents or pharmaceutical alternatives). The importance of bioequivalence studies is increasing also due to the large growth of the production and consumption of generic products. Generic products represent approximately 50 % of the whole consumption in many European countries and USA. The search output of bioequivalence study is together with the pharmaceutical quality data of medical product one of the main part of the registration file submitted to a national regulatory authorities. The registration of generic products does not demand complicated and expensive clinical study contrary to original product. The comparison of the original and the generic product via bioequivalence study is suggested as sufficient. The aim of this article is to provide to a medical public a summary about the types of bioequivalence studies, their range, rules of their practise and let them gain their own attitude to this question.

  8. 16 CFR 1702.2 - Procedural requirements and recommendations.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Procedural requirements and recommendations...; PETITION PROCEDURES AND REQUIREMENTS § 1702.2 Procedural requirements and recommendations. (a) Requirements... deficiency, and explain that the petition may be resubmitted when the deficiency is corrected. (c) Procedural...

  9. 31 CFR 132.5 - Policies and procedures required.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Policies and procedures required. 132... FUNDING OF UNLAWFUL INTERNET GAMBLING § 132.5 Policies and procedures required. (a) All non-exempt participants in designated payment systems shall establish and implement written policies and procedures...

  10. 40 CFR 725.150 - Procedural requirements for this subpart.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Procedural requirements for this subpart. 725.150 Section 725.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Commercial Activities Notification Requirements § 725.150 Procedural requirements for this subpart. General...

  11. 40 CFR 725.350 - Procedural requirements for this subpart.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Procedural requirements for this subpart. 725.350 Section 725.350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... for Test Marketing § 725.350 Procedural requirements for this subpart. General requirements for all...

  12. 40 CFR 725.250 - Procedural requirements for the TERA.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Procedural requirements for the TERA. 725.250 Section 725.250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... and Development Activities § 725.250 Procedural requirements for the TERA. General requirements for...

  13. 46 CFR 67.171 - Deletion; requirement and procedure.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Deletion; requirement and procedure. 67.171 Section 67...; Requirement for Exchange, Replacement, Deletion, Cancellation § 67.171 Deletion; requirement and procedure. (a... provided in § 67.161, and the vessel is subject to deletion from the roll of actively documented vessels...

  14. The importance of bioequivalence study: focus on clopidogrel

    Directory of Open Access Journals (Sweden)

    Arini Setiawati

    2011-05-01

    Full Text Available Bioequivalence (BE study is required to show whether a generic copy product can be interchangeable with the brand innovator product. The aim of this article is to provide the rationale for conducting BE studies, the main products requiring BE studies, the design and conduct of BE studies in general, with focus on clopidogrel. All of the clopidogrel generic products in Indonesia have been shown to be BE to the innovator product Plavix® and they contain API (active pharmaceutical ingredient clopidogrel form 1 that complies with USP 30, 1997 requirements: the R-enantiomer content is not more than 1%. A proof that bioequivalence (BE means therapeutic equivalence (TE is also provided for cardiovascular drugs. Clopidogrel has 2 polymorphic forms, form 1 and form 2, which have the same indications. At least one pivotal study of clopidogrel, CAPRIE, used clopidogrel form 1. An atherothrombotic event may be associated with clopidogrel resistance, which occur in about 4 to 30% of patients treated with conventional doses of clopidogrel. (Med J Indones 2011; 20:149-53Keywords: bioequivalent, clopidogrel

  15. 12 CFR 233.5 - Policies and procedures required.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Policies and procedures required. 233.5 Section... implement written policies and procedures reasonably designed to identify and block or otherwise prevent or... this section if— (1) It relies on and complies with the written policies and procedures of the...

  16. 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.

  17. 47 CFR 74.432 - Licensing requirements and procedures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Licensing requirements and procedures. 74.432... Broadcast Stations § 74.432 Licensing requirements and procedures. (a) A license for a remote pickup station... previously-licensed transmitters within the system license. Applications submitted for system licensing prior...

  18. 47 CFR 74.832 - Licensing requirements and procedures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Licensing requirements and procedures. 74.832... Stations § 74.832 Licensing requirements and procedures. (a) A license authorizing operation of one or more... to the same community. Licensing of low power auxiliary stations for use with a specific broadcast...

  19. Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets.

    Science.gov (United States)

    Al-Tabakha, Moawia M; Fahelelbom, Khairi M S; Obaid, Dana Emad Eddin; Sayed, Sadik

    2017-05-20

    Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes, including in vitro bioequivalence performance. Five generic products (T1, T2, T3, T4, and T5) containing combination of amoxicillin trihydrate and potassium clavulanate as 1 g strength present in immediate release tablets were compared to the reference listed drug product Augmentin® (R) for weight variation, friability, resistance to crushing, and chemical content of amoxicillin. Difference (ƒ1) and similarity (ƒ2) factors were calculated to assess in vitro bioequivalence requirements. The tablets from different products have shown compliance with the pharmacopeial requirements of the performed tests. The measured resistance to crushing of tablets did not influence the dissolution time. Three generic products released more than 85% of amoxicillin by the first 15 min as did the reference product and were considered as bioequivalent products. T1 and T4 had ƒ1 values of 16.5% and 25.4% respectively and their ƒ2 values were 44.5 and 34.6 respectively, indicating failure to meet in vitro bioequivalence requirements. Tablet formulations can play an important role in achieving bioequivalence. Independent investigations such as this study serve as an important tool to reveal possible inferior or noncompliant products that may find their way to the market.

  20. International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

    Science.gov (United States)

    Davit, Barbara; Braddy, April C; Conner, Dale P; Yu, Lawrence X

    2013-10-01

    The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.

  1. 5 CFR 838.1121 - Procedures and requirements.

    Science.gov (United States)

    2010-01-01

    ... REGULATIONS (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Under the Child Abuse Accountability Act Application, Processing, and Payment Procedures and Documentation Requirements § 838.1121... requirements applicable to legal process under part 581 of this chapter apply to OPM's administration of child...

  2. Overview of the European Medicines Agency's Development of Product-Specific Bioequivalence Guidelines.

    Science.gov (United States)

    Sullivan, Jane O'; Blake, Kevin; Berntgen, Michael; Salmonson, Tomas; Welink, Jan

    2017-12-05

    The European Medicines Agency's (EMA) product-specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision-making. Since their introduction in 2013, EMA product-specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agency's experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  3. Comparative bioequivalence assessment of aspirin tablets marketed ...

    African Journals Online (AJOL)

    Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

  4. Euratom's accounting procedures to comply with IAEA requirements

    International Nuclear Information System (INIS)

    Kschwendt, H.

    1980-01-01

    The accounting concept used by the operators for nuclear materials accountancy is different from the evaluation concept used by IAEA. Euratom integrated these two concepts thus allowing for an automatic transformation from the one to the other concept (establishment of reports to IAEA by computer). Particular procedures have been developed to ensure the corrections of the accountancy in both concepts and to perform the retrospective corrections as required by IAEA. 4 refs

  5. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Science.gov (United States)

    2013-12-05

    ...] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted... guidance for industry entitled ``Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted... draft guidance for industry entitled ``Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

  6. [Required procedure for nominal data files processing in biomedical research].

    Science.gov (United States)

    Chambon-Savanovitch, C; Dubray, C; Albuisson, E; Sauvant, M P

    2001-12-01

    To date, biomedical research using nominal data files for the data collection, data acquisition or data processing has had to comply with 2 French laws (Law of December, 20, 1988, modified, relating to the protection of patients participating in biomedical research, and the Law of January, 6, 1978, completed by the Law of July 1, 1994 n degrees 94-548, chapter V bis). This later law dictates rules not only for the establishment of nominal data files, but also confer individual rights to filed persons. These regulations concern epidemiological research, clinical trials, drug watch studies and economic health research. In this note, we describe the obligations and specific general and simplified procedure required for conducting biomedical research. Included in the requirements are an information and authorization procedure with the local and national consultative committees on data processing in biomedical research (CCTIRS, Comité Consultatif sur le Traitement de l'Information en Recherche Biomédicale, and CNIL, Commission Nationale Informatique et Libertés).

  7. A limited sampling approach in bioequivalence studies: application to long half-life drugs and replicate design studies.

    Science.gov (United States)

    Mahmood, I; Mahayni, H

    1999-06-01

    The objectives of this study was to develop a limited sampling model (LSM) to predict the area under the curve (AUC) and the maximum plasma concentration (Cmax) for the assessment of bioequivalence studies. Two drugs (A and B) were selected for this purpose. Drug A was chosen to test bioequivalence of two formulations with a long half-life (> 35 hours), whereas drug B was chosen to test the bioequivalence of two formulations (half-life = 12 hrs) with a replicate design study. The LSM for both drugs was developed using 5 blood samples each from 15 healthy subjects. The relationship between plasma concentration (independent variable) at selected time points with the AUC or Cmax (dependent variable) was evaluated by multiple linear regression analysis. The multiple linear regression which gave the best correlation coefficient (r) for 5 sampling time vs AUC or Cmax was chosen as the LSM. The predicted AUC and Cmax from the LSM were then used to assess bioequivalence of two different formulations of each drug following a single oral dose. The model provided good estimates of both AUC and Cmax for both drugs. The 90% confidence intervals on log-transformed observed and predicted AUC and Cmax were comparable for both drugs. The method described here may be used to estimate AUC and Cmax for bioequivalence studies for drugs with long half-lives or for highly variable drugs which may require replicate design studies without detailed blood sampling.

  8. Bioequivalence Evaluations of Generic Dry Powder Inhaler Drug Products: Similarities and Differences Between Japan, USA, and the European Union.

    Science.gov (United States)

    Kuribayashi, Ryosuke; Yamaguchi, Toru; Sako, Hanaka; Takishita, Tomoko; Takagi, Kazunori

    2017-03-01

    In Japan, the development of generic oral dry powder inhaler (DPI) drug products for marketing approval has recently increased. The Pharmaceuticals and Medical Devices Agency (PMDA) considers the required data for each drug product in the consultation meeting. However, guidelines for DPI drug products have been published by the US Food and Drug Administration and the European Medicines Agency. Recently, the basic principles of bioequivalence evaluations of generic DPI drug products were published in March 2016 by the Ministry of Health, Labour and Welfare. The document mainly outlines the current understanding regarding the bioequivalence evaluations of generic DPI drug products based on knowledge from PMDA consultation meetings. In this review, we compared the bioequivalence evaluations of DPI drug products among Japan, USA, and the European Union and discuss future development of generic DPI drug products in Japan.

  9. Consumer's risk in the EMA and FDA regulatory approaches for bioequivalence in highly variable drugs.

    Science.gov (United States)

    Muñoz, Joel; Alcaide, Daniel; Ocaña, Jordi

    2016-05-30

    The 2010 US Food and Drug Administration and European Medicines Agency regulatory approaches to establish bioequivalence in highly variable drugs are both based on linearly scaling the bioequivalence limits, both take a 'scaled average bioequivalence' approach. The present paper corroborates previous work suggesting that none of them adequately controls type I error or consumer's risk, so they result in invalid test procedures in the neighbourhood of a within-subject coefficient of variation osf 30% for the reference (R) formulation. The problem is particularly serious in the US Food and Drug Administration regulation, but it is also appreciable in the European Medicines Agency one. For the partially replicated TRR/RTR/RRT and the replicated TRTR/RTRT crossover designs, we quantify these type I error problems by means of a simulation study, discuss their possible causes and propose straightforward improvements on both regulatory procedures that improve their type I error control while maintaining an adequate power. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

    Science.gov (United States)

    García-Arieta, Alfredo; Ferrero-Cafiero, Juan Manuel; Puntes, Montse; Gich, Ignasi; Morales-Alcelay, Susana; Tarré, Maite; Font, Xavier; Antonijoan, Rosa Maria

    2016-05-01

    The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Blinded sample size re-estimation in crossover bioequivalence trials.

    Science.gov (United States)

    Golkowski, Daniel; Friede, Tim; Kieser, Meinhard

    2014-01-01

    In drug development, bioequivalence studies are used to indirectly demonstrate clinical equivalence of a test formulation and a reference formulation of a specific drug by establishing their equivalence in bioavailability. These studies are typically run as crossover studies. In the planning phase of such trials, investigators and sponsors are often faced with a high variability in the coefficients of variation of the typical pharmacokinetic endpoints such as the area under the concentration curve or the maximum plasma concentration. Adaptive designs have recently been considered to deal with this uncertainty by adjusting the sample size based on the accumulating data. Because regulators generally favor sample size re-estimation procedures that maintain the blinding of the treatment allocations throughout the trial, we propose in this paper a blinded sample size re-estimation strategy and investigate its error rates. We show that the procedure, although blinded, can lead to some inflation of the type I error rate. In the context of an example, we demonstrate how this inflation of the significance level can be adjusted for to achieve control of the type I error rate at a pre-specified level. Furthermore, some refinements of the re-estimation procedure are proposed to improve the power properties, in particular in scenarios with small sample sizes. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets (50mg) in healthy volunteers.

    Science.gov (United States)

    Ali, Huma; Shoaib, Muhammad Harris; Zafar, Farya; Hanif, Muhammad; Bushra, Rabia; Naz, Asia; Khursheed, Raheela

    2016-09-01

    This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test (F4) tablet formulation with reference product (Caflam). Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 µg.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test (F4) and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples (20µL) were injected using the validated HPLC method. Various pharmacokinetic parameters (compartmental and noncompartmental) were estimated using KineticaTM 4.4.1 (Thermo Electron Corp. USA). Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for Cmaxcalc, Tmaxcalc, AUC0-∞, AUCtot and AUClast using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC0-∞ (0.997-1.024), AUCtot (1.004-1.031), AUClast (0.997 -1.024), Cmaxcalc (0.994-1.007) and Tmaxcalc (0.996-1.013) for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated.

  13. Bioequivalence: the regulatory career of a pharmaceutical concept.

    Science.gov (United States)

    Carpenter, Daniel; Tobbell, Dominique A

    2011-01-01

    Generic drugs cannot be marketed without regulatory and clinical demonstration of "bioequivalence." The authors argue that the concept of "bioequivalence" is a joint regulatory and scientific creation, not purely a technical concept, and not purely a legal concept. It developed at the interstices of networks of pharmacologists, regulators, food and drug lawyers, and American and European policy makers interested in "generic" drugs. This article provides a situated perspective on the history of bioequivalence, which emphasizes the shaping role of the state upon scientific processes, networks of regulators and scientists, and the centrality of transnational dynamics in the formation of drug regulatory standards.

  14. Bioequivalence: The Regulatory Career of a Pharmaceutical Concept

    OpenAIRE

    Carpenter, Daniel Paul; Tobbell, Dominique A.

    2011-01-01

    Generic drugs cannot be marketed without regulatory and clinical demonstration of "bioequivalence." The authors argue that the concept of "bioequivalence" is a joint regulatory and scientific creation, not purely a technical concept, and not purely a legal concept. It developed at the interstices of networks of pharmacologists, regulators, food and drug lawyers, and American and European policy makers interested in "generic" drugs. This article provides a situated perspective on the history o...

  15. Optimum number of procedures required to achieve procedural skills competency in internal medicine residents.

    Science.gov (United States)

    Tariq, Muhammad; Bhulani, Nizar; Jafferani, Asif; Naeem, Quratulain; Ahsan, Syed; Motiwala, Afaq; van Dalen, Jan; Hamid, Saeed

    2015-10-23

    Procedural skills training forms an essential, yet difficult to assess, component of an Internal Medicine Residency Program. We report the development of process of documentation and assessment of procedural skills training. An explanatory sequential mixed methods design was adopted where both quantitative and qualitative information was collected sequentially. A survey was conducted within the Department of Internal Medicine at The Aga Khan University Hospital, Karachi, Pakistan to determine the optimum number of procedures needed to be performed by residents at each year of residency. Respondents included both faculty and the residents in the Department. Thereafter, all responses were compiled and later scrutinized by a focus group comprising of a mix of faculty from various subspecialties and resident representatives. A total of 64 responses were obtained. A significant difference was found in eight procedural skills' status between residents and faculty, though none of these were significant after accounting for multiple consecutive testing. However, the results were reviewed and a consensus for the procedures needed was developed through a focus group. A finalized procedural list was generated to determine: (a) the minimum number of times each procedure needed to be performed by the resident before deemed competent; (b) the level of competency for each procedure for respective year of residency. We conclude that the opinion of both the residents and the faculty as key stakeholders is vital to determine the number of procedures to be performed during an Internal Medicine Residency. Documentation of procedural competency development during the training would make the system more objective and hence reproducible. A log book was designed consisting of minimum number of procedures to be performed before attaining competency.

  16. Bioequivalence of three florfenicol preparations in broilers

    Directory of Open Access Journals (Sweden)

    Husamettin Ekici

    2014-12-01

    Full Text Available This study was aimed to determine the bioequivalence of three different preparations of florfenicol using non-drugged broiler chickens. A total of 28 broiler chickens aging 30-day were divided into four equal groups; these were Group I, II, III, and IV. The birds of Group I (for effective substance were given intravenous (i.v. administration of florfenicol dosed at 40 mg/kg body weight (b.wt.. The birds of Group II (for reference drug, Group III (for test-1 drug, and Group IV (for test-2 drug received florfenicol preparations with water (dosed at 40 mg/kg b.wt. through intracrop administration. Blood samples were collected periodically from the birds of all four groups, and blood plasma was separated. Levels of florfenicol and its metabolite (florfenicol amine in the plasma were measured by High Performance Liquid Chromatography (HPLC. In this study, the limit of detection (LOD for florfenicol and florfenicol amine were recorded as 0.017 and 0.78 µg/mL, respectively. On the other hand, the recovery of florfenicol and florfenicol amine were 83.4-84.6 and 82.2-83.8%, respectively. Based on the values of area under the curve (AUC, maximum concentration (Cmax, and time to maximum concentration (Tmax, test-1 drug was found to be acceptable, whereas test-2 drug was remained below the acceptable limits (80-125% of AUC and Cmax. Thus, it was concluded that test-1 drug was bioequivalent as compared to the reference drug.

  17. 40 CFR 92.123 - Test procedure; general requirements.

    Science.gov (United States)

    2010-07-01

    ... the test. Auxiliary fan(s) may be used to maintain engine cooling during operation on the dynamometer... smoke. (1) In the raw exhaust sampling procedure, sample is collected directly from the exhaust stream... of another raw exhaust sample. The fuel flow rate for each throttle setting is measured. (2) For...

  18. 7 CFR 70.110 - Requirements for sanitation, facilities, and operating procedures in official plants.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Requirements for sanitation, facilities, and operating... Requirements for sanitation, facilities, and operating procedures in official plants. (a) The requirements for sanitation, facilities, and operating procedures in official plants shall be the applicable provisions stated...

  19. 5 CFR 1208.11 - Choice of procedure under USERRA; exhaustion requirement.

    Science.gov (United States)

    2010-01-01

    ...; exhaustion requirement. 1208.11 Section 1208.11 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD... procedure under USERRA; exhaustion requirement. (a) Choice of procedure. An appellant may file a USERRA... under 38 U.S.C. 4322. (b) Exhaustion requirement. If an appellant files a complaint with the Secretary...

  20. 38 CFR 36.4220 - Substantive and procedural requirements; waiver.

    Science.gov (United States)

    2010-07-01

    ... OF VETERANS AFFAIRS (CONTINUED) LOAN GUARANTY Guaranty of Loans to Veterans to Purchase Manufactured... default. (5) The requirement in § 36.4280 that a holder give 30 days advance notice of its intention to...

  1. Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology

    DEFF Research Database (Denmark)

    Garcia Ortiz, Patricia Elodia; Hansen, S H; Shah, Surendra P.

    2011-01-01

    To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

  2. Are marketed topical metronidazole creamas bioequivalent ? Evaluation by in vivo microdialysis sampling and tape stripping methodology

    DEFF Research Database (Denmark)

    Ortiz, P. Garcia; Hansen, Steen Honore'; Shah, V. P.

    2011-01-01

    To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence.......To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

  3. Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology

    DEFF Research Database (Denmark)

    Garcia Ortiz, Patricia Elodia; Hansen, S H; Shah, Surendra P.

    2011-01-01

    To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence.......To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

  4. 30 CFR 14.4 - Application procedures and requirements.

    Science.gov (United States)

    2010-07-01

    ...) MSHA will determine if testing, additional information, samples, or material is required to evaluate an... Section 14.4 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING... and fabric for metal cord belts. (2) The name, address, and telephone number of the applicant's...

  5. Review of load rating and posting procedures and requirements.

    Science.gov (United States)

    2014-12-01

    All states are required to load rate and post bridges in order to comply with federal standards. Load ratings are performed in order to : determine the safe live load capacity of a bridge, considering the existing conditions of the bridge. Based on t...

  6. A perspective for biowaivers of human bioequivalence studies on the basis of the combination of the ratio of AUC to the dose and the biopharmaceutics classification system.

    Science.gov (United States)

    Sakuma, Shinji; Tachiki, Hidehisa; Uchiyama, Hitoshi; Fukui, Yasunobu; Takeuchi, Naohiro; Kumamoto, Kazuo; Satoh, Tomonori; Yamamoto, Yoshinobu; Ishii, Emi; Sakai, Yoshiyuki; Takeuchi, Susumu; Sugita, Masaru; Yamashita, Shinji

    2011-08-01

    The ratio of AUC to the dose (AUC/dose) was previously found as a parameter that predicts a risk of bioinequivalence of oral drug products. On the basis of the combination of this parameter and the biopharmaceutics classification system (BCS), a perspective for biowaivers of human bioequivalence studies is discussed. Databases of bioequivalence studies using immediate-release solid oral dosage forms were disclosed by 6 Japanese generic pharmaceutical companies, and the number of subjects required for demonstrating bioequivalence between generic and reference products was plotted as a function of AUC/dose for each BCS category. A small variation in the number of subjects was constantly observed in bioequivalence studies using dosage forms containing an identical BCS class 1 or class 3 drug, even though formulations of the generic product differ between companies. The variation was extremely enlarged when the drugs were substituted with BCS class 2 drugs. Rate-determining steps in oral absorption of highly water-soluble BCS class 1 and class 3 drugs are independent of formulations when there is no significant difference in the in vitro dissolution profiles between formulations. The small variation observed for both BCS categories indicates that the number of subjects converges into one value for each drug. Our analysis indicates the appropriateness of biowaiver of bioequivalence studies for immediate-release solid oral dosage forms containing not only BCS class 1 drugs but also class 3 drugs.

  7. 34 CFR 370.43 - What requirement applies to the use of mediation procedures?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false What requirement applies to the use of mediation... applies to the use of mediation procedures? (a) Each designated agency shall implement procedures designed to ensure that, to the maximum extent possible, good faith negotiations and mediation procedures are...

  8. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  9. 40 CFR 725.450 - Procedural requirements for the Tier II exemption.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Procedural requirements for the Tier II exemption. 725.450 Section 725.450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... General Exemptions for New Microorganisms § 725.450 Procedural requirements for the Tier II exemption...

  10. Very rapid dissolution is not needed to guarantee bioequivalence for biopharmaceutics classification system (BCS) I drugs.

    Science.gov (United States)

    Kortejärvi, H; Shawahna, R; Koski, A; Malkki, J; Ojala, K; Yliperttula, M

    2010-02-01

    Currently, the EMEA, FDA, and WHO as regulatory authorities accept rapidly dissolving (>85% dissolved in 30 min) biopharmaceutics classification system (BCS) I drug products for biowaiver candidates. In the draft EMEA guideline the requirement has been set tighter, that is, the drug product should be very rapidly dissolving (>85% dissolved in 15 min) to be eligible for a biowaiver. Pharmacokinetic modeling of 32 BCS I drugs was performed to demonstrate that very rapid dissolution is not necessary to guarantee bioequivalence for them. Rapid dissolution and similar dissolution profiles are sufficient criteria for all BCS I drugs. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

  11. Evaluation procedures for single axis sinusoidal test to design spectrum requirements

    International Nuclear Information System (INIS)

    Sun, P.C.; Javid, A.

    1983-01-01

    Two simple procedures are provided in this paper for the purpose of evaluating the adequacy of a single frequency single axis test. For the purpose of evaluating the adequacy of single frequency test to meet broad-band response spectrum requirements, the proposed procedure is based on the equivalence of maximum response of a dynamic system when it is subjected to either type of design input. The required information used for the evaluation is usually recorded and available in the test report. This procedure is applicable to systems with or without closely-spaced modes. When evaluating against broad-band design spectra and multi-axes requirements, an empirical procedure is proposed and it has been found conservative. These two proposed procedures provide a quick assessment on the adequacy of a single frequency test performed earlier. The use of these procedures may eliminate the need of expensive and time consuming equipment re-testing. (orig./HP)

  12. L-T4 bioequivalence and hormone replacement studies via feedback control simulations.

    Science.gov (United States)

    Eisenberg, Marisa; Samuels, Mary; DiStefano, Joseph J

    2006-12-01

    FDA Guidance for testing bioequivalence of levothyroxine (L-T(4)) preparations has been challenged by several groups, based on multiple issues. The efficacy of single versus combined hormone therapy also is receiving additional scrutiny. To examine these concerns, we developed a new nonlinear feedback system simulation model of whole-body regulation mechanisms involving dynamics of T(3), T(4), TSH, plasma protein binding, extravascular regulatory enzyme systems, and the hypothalamic-pituitary-thyroid axis, all quantified from human data. To address bioequivalence, we explored how to best account for varying and unmeasured endogenous T(4) following dosing with exogenous oral L-T(4) in euthyroid volunteers in required pharmacokinetic (PK) studies, by simulating various dosing scenarios and developing a new and simple correction method. We computed and assessed dosing error effects and baseline corrections using simulator-predicted endogenous T(4) level variations, due to actual closed-loop effects, and compared these with approximate corrections computed directly from PK data. Predicted dose-responses were quite linear, and for constant baseline, 7-day half-life, and our new formula-correction methods, we established some bounds on bioequivalent dosages. Simulated replacement after thyroidectomy required 141 microg L-T(4) only to normalize T(3) tissue levels and 162 microg L-T(4) to normalize plasma T(3) levels. A combined dose of approximately 103 microg L-T(4) plus approximately 6 microg T(3) ( approximately 18:1 ratio) was needed to normalize both plasma T(3) and T(4) and average tissue T(3) levels. However, simulated average tissue T(3) levels were normalized with standard L-T(4)-only therapy, and plasma T(3) levels were still within the normal range. We suggest a simple and more accurate correction for endogenous T(4) in PK studies. Current standard L-T(4)-only treatment is supported for routine replacement needs.

  13. Bioequivalence of ciprofloxacin tablet formulations assessed in Indonesian volunteers.

    Science.gov (United States)

    Harahap, Y; Prasaja, B; Indriati, E; Lusthom, W; Lipin

    2007-06-01

    Determination of the bioequivalence of two ciprofloxacin tablet formulations (test formulation manufactured by Novell Pharmaceutical Laboratories, Indonesia, reference formulation from Quimica Farmaceutica Bayer, Spain). 24 healthy volunteers received each of the two ciprofloxacin formulations at a dose of 500 mg in a 2-way crossover design. Blood samples were obtained prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and24h after drug administration. Plasma concentrations of ciprofloxacin were monitored using high-performance liquid chromatography over a period of 24 h after administration. The pharmacokinetics parameter AUC0-24h, AUC0-infinity and Cmax were tested for bioequivalence after log-transformation of data and ratios of tmax were evaluated non-parametrically. The point estimates and 90% confidence intervals for AUC0-24h, AUC0-infinity and Cmax were 97.55% (92.71 - 102.6%), 97.63% (92.90 - 102.59%) and 95.84% (89.95 - 102.10%), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. These results indicate that two medications of ciprofloxacin are bioequivalent and, thus, may be prescribed interchangeably.

  14. Achieving Procedural Competence during Nephrology Fellowship Training: Current Requirements and Educational Research.

    Science.gov (United States)

    Clark, Edward; Barsuk, Jeffrey H; Karpinski, Jolanta; McQuillan, Rory

    2016-12-07

    Concerns have previously been raised as to whether training programs are ensuring that nephrology fellows achieve competence in the procedural skills required for independent practice. We sought to review the current requirements for procedural training as well as educational research pertaining to achieving competence in the core nephrology procedures of nontunneled (temporary) hemodialysis catheter insertion and percutaneous kidney biopsy. At this time, there is no universal approach to procedural training and assessment during nephrology fellowship. Nonetheless, simulation-based mastery learning programs have been shown to be effective in improving fellows' skills in nontunneled (temporary) hemodialysis catheter insertion and should be provided by all nephrology training programs. For percutaneous kidney biopsy, the development and evaluation of inexpensive simulators are a promising starting point for future study. Current practice with respect to procedural training during nephrology fellowship remains imperfect; however, the ongoing shift toward competency-based evaluation provides opportunities to refocus on improvement. Copyright © 2016 by the American Society of Nephrology.

  15. 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

  16. 46 CFR 197.206 - Substitutes for required equipment, materials, apparatus, arrangements, procedures, or tests.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Substitutes for required equipment, materials, apparatus, arrangements, procedures, or tests. 197.206 Section 197.206 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... Operations General § 197.206 Substitutes for required equipment, materials, apparatus, arrangements...

  17. Generics Substitution, Bioequivalence Standards, and International Oversight: Complex Issues Facing the FDA.

    Science.gov (United States)

    Bate, Roger; Mathur, Aparna; Lever, Harry M; Thakur, Dinesh; Graedon, Joe; Cooperman, Tod; Mason, Preston; Fox, Erin R

    2016-03-01

    The regulations for assessing the quality of generic drugs and their bioequivalence to innovator products are outdated and need to be substantially modernized. There are multiple reasons why these changes are needed, including: (i) the regulations remain largely unchanged since the passage of the Hatch-Waxman Act in 1984; (ii) medication therapies have become substantially more complex over the three decades since the passage of the Act; (iii) a switch from an innovator drug to a generic drug, or switching from one generic to another, is not a benign process - there is substantial clinical professional judgment involved and in some instances these decisions should be better informed; and (iv) pharmaceutical ingredients for finished products, whether innovator or generic, are from multiple sources of supply, adding variability in their production, and which may not be accounted for in specification tolerances. When these elements are viewed together, they clearly suggest that more transparency of responsible manufacturers in product labels and updated standards for bioequivalence are required. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Guidelines on the facilities required for minor surgical procedures and minimal access interventions.

    LENUS (Irish Health Repository)

    Humphreys, H

    2012-02-01

    There have been many changes in healthcare provision in recent years, including the delivery of some surgical services in primary care or in day surgery centres, which were previously provided by acute hospitals. Developments in the fields of interventional radiology and cardiology have further expanded the range and complexity of procedures undertaken in these settings. In the face of these changes there is a need to define from an infection prevention and control perspective the basic physical requirements for facilities in which such surgical procedures may be carried out. Under the auspices of the Healthcare Infection Society, we have developed the following recommendations for those designing new facilities or upgrading existing facilities. These draw upon best practice, available evidence, other guidelines where appropriate, and expert consensus to provide sensible and feasible advice. An attempt is also made to define minimal access interventions and minor surgical procedures. For minimal access interventions, including interventional radiology, new facilities should be mechanically ventilated to achieve 15 air changes per hour but natural ventilation is satisfactory for minor procedures. All procedures should involve a checklist and operators should be appropriately trained. There is also a need for prospective surveillance to accurately determine the post-procedure infection rate. Finally, there is a requirement for appropriate applied research to develop the evidence base required to support subsequent iterations of this guidance.

  20. "Pharmacodynamically evaluated bioequivalence of two preparations of Enalapril Maleate "

    Directory of Open Access Journals (Sweden)

    "Tajerzadeh H

    2001-07-01

    Full Text Available The bioequivalence of two preparations of enalapril maleate (20 mg tablets manufactured in Iran has been exploited in reference to a standard preparation (Xanef 20 tablets, MSD, Germany in 14 healthy volunteers. Following oral dosing of a single tablet of each of test and standard products, as a randomized crossover design with 10-day washout intervals, the blood samples were collected in predetermined time points and using a synthetic substrate, Hippuryl-Histidy-Leucine (HHL, the release of hippuric acid from the substrate was determined as Angiotensin-Converting-Enzyme (ACE activity of serum fractions. The percent of ACE inhibition in each sample was calculated and plotted against time, from which three pharmacodynamic parameters, i.e. Emax, tmax and AUC0-24 were derived. The results of statistical comparison of these parameters showed that both of the test preparations are bioequivalent with reference standard preparation.

  1. Summary workshop report: bioequivalence, biopharmaceutics classification system, and beyond.

    Science.gov (United States)

    Polli, James E; Abrahamsson, Bertil S I; Yu, Lawrence X; Amidon, Gordon L; Baldoni, John M; Cook, Jack A; Fackler, Paul; Hartauer, Kerry; Johnston, Gordon; Krill, Steve L; Lipper, Robert A; Malick, Waseem A; Shah, Vinod P; Sun, Duxin; Winkle, Helen N; Wu, Yunhui; Zhang, Hua

    2008-06-01

    The workshop "Bioequivalence, Biopharmaceutics Classification System, and Beyond" was held May 21-23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance.

  2. "Pharmacodynamically evaluated bioequivalence of two preparations of Enalapril Maleate "

    OpenAIRE

    "Tajerzadeh H; Hamidi M; Rouini MR; Shahverdi M; Ghaiumi A "

    2001-01-01

    The bioequivalence of two preparations of enalapril maleate (20 mg tablets) manufactured in Iran has been exploited in reference to a standard preparation (Xanef 20 tablets, MSD, Germany) in 14 healthy volunteers. Following oral dosing of a single tablet of each of test and standard products, as a randomized crossover design with 10-day washout intervals, the blood samples were collected in predetermined time points and using a synthetic substrate, Hippuryl-Histidy-Leucine (HHL), the release ...

  3. Risk and safety requirements for diagnostic and therapeutic procedures in allergology: World Allergy Organization Statement

    Directory of Open Access Journals (Sweden)

    Marek L. Kowalski

    2016-10-01

    Full Text Available Abstract One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing, deliberate induction in the office of allergic symptoms to offending compounds (provocation tests or intentional application of potentially dangerous substances (allergy vaccine to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO, representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established

  4. 21 CFR 111.16 - What are the requirements under this subpart C for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart C for written procedures? 111.16 Section 111.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  5. 21 CFR 111.103 - What are the requirements under this subpart F for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart F for written procedures? 111.103 Section 111.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  6. 21 CFR 111.503 - What are the requirements under this subpart N for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart N for written procedures? 111.503 Section 111.503 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  7. 21 CFR 111.403 - What are the requirements under this subpart L for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart L for written procedures? 111.403 Section 111.403 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  8. 21 CFR 111.353 - What are the requirements under this subpart K for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart K for written procedures? 111.353 Section 111.353 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  9. 21 CFR 111.453 - What are the requirements under this subpart for M written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart for M written procedures? 111.453 Section 111.453 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  10. 21 CFR 111.8 - What are the requirements under this subpart B for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart B for written procedures? 111.8 Section 111.8 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  11. 21 CFR 111.153 - What are the requirements under this subpart G for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart G for written procedures? 111.153 Section 111.153 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  12. 21 CFR 111.25 - What are the requirements under this subpart D for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart D for written procedures? 111.25 Section 111.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  13. 21 CFR 111.553 - What are the requirements under this subpart O for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart O for written procedures? 111.553 Section 111.553 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  14. 21 CFR 111.303 - What are the requirements under this subpart J for written procedures?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart J for written procedures? 111.303 Section 111.303 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

  15. 78 FR 79058 - Proposed Information Collection Request; Notice of New Requirements and Procedures for Grant...

    Science.gov (United States)

    2013-12-27

    ... system. Users must complete a user request form and provide the following information: full name, work... user will return the form to receive their login credentials. DOT Office of Financial Management... Information Collection Request; Notice of New Requirements and Procedures for Grant Payment Request Submission...

  16. 27 CFR 479.26 - Alternate methods or procedures; emergency variations from requirements.

    Science.gov (United States)

    2010-04-01

    ... AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN OTHER FIREARMS Administrative and Miscellaneous...) The alternate method or procedure will not be contrary to any provision of law and will not result in... provisions of law. Variations from requirements granted under this paragraph are conditioned on compliance...

  17. 7 CFR Appendix to Subpart C of... - Accounting Methods and Procedures Required of All Borrowers

    Science.gov (United States)

    2010-01-01

    ...—Accounting Methods and Procedures Required of All Borrowers All borrowers shall maintain and keep their books...), and (c) Expected long-term rate of return on plan assets. 7. The assumed health care cost trend rate(s... charges) and a general description of the direction and pattern of change in the assumed trend rates...

  18. 15 CFR 30.35 - Procedure for shipments exempt from filing requirements.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Procedure for shipments exempt from filing requirements. 30.35 Section 30.35 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Exemptions From the...

  19. Computer-Based Procedures for Field Workers in Nuclear Power Plants: Development of a Model of Procedure Usage and Identification of Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Katya Le Blanc; Johanna Oxstrand

    2012-04-01

    The nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. As a step toward the goal of improving procedure use performance, researchers, together with the nuclear industry, have been looking at replacing the current paper-based procedures with computer-based procedure systems. The concept of computer-based procedures is not new by any means; however most research has focused on procedures used in the main control room. Procedures reviewed in these efforts are mainly emergency operating procedures and normal operating procedures. Based on lessons learned for these previous efforts we are now exploring a more unknown application for computer based procedures - field procedures, i.e. procedures used by nuclear equipment operators and maintenance technicians. The Idaho National Laboratory and participants from the U.S. commercial nuclear industry are collaborating in an applied research effort with the objective of developing requirements and specifications for a computer-based procedure system to be used by field workers. The goal is to identify the types of human errors that can be mitigated by using computer-based procedures and how to best design the computer-based procedures to do so. This paper describes the development of a Model of Procedure Use and the qualitative study on which the model is based. The study was conducted in collaboration with four nuclear utilities and five research institutes. During the qualitative study and the model development requirements and for computer-based procedures were identified.

  20. On the Need / utility of Flexibilization Procedural by Judge of Procedure System in Brazil : An Analysis Required

    OpenAIRE

    Bruna Rocha Passos

    2016-01-01

    This study addresses the phenomenon of procedural flexibility, one of the innovations provided for in the New Civil Procedure Code, introduced in Brazil by Law No. 13,105 /2015. The study begins with the presentation of models of procedural systems and their characteristics. Breaks, then to the study of existing procedural flexibility models in other jurisdictions, with a special analysis of the main specificities of flexible models adopted by England, USA and Portugal. Then, it is the analys...

  1. Evaluation procedure of software requirements specification for digital I and C of KNGR

    International Nuclear Information System (INIS)

    Lee, Jang Soo; Park, Jong Kyun; Lee, Ki Young; Kim, Jang Yeol; Cheon, Se Woo

    2001-06-01

    The accuracy of the specification of requirements of a digital system is of prime importance to the acceptance and success of the system. The development, use, and regulation of computer systems in nuclear reactor Instrumentation and Control (I and C) systems to enhance reliability and safety is a complex issue. This report is one of a series of reports from the Korean Next Generation Reactor (KNGR) Software Safety Verification and Validation (SSVV) Task, Korea Atomic Energy Research Institute, which investigates different aspects of computer software in reactor I and C systems, and describes the engineering procedures for developing such a software. The purpose of this guideline is to give the software safety evaluator the trail map between the code and standards layer and the design methodology and documents layer for the software important to safety in nuclear power plants. Recently, the requirements specification of safety-critical software systems and safety analysis of them are being recognized as one of the important issues in the software life cycle, and being developed new regulatory positions and standards by the regulatory and the standardization organizations such as IAEA, IEC, and IEEE. We presented the procedure for evaluating the software requirements specifications of the KNGR protection systems. We believe it can be useful for both licenser and licensee to conduct an evaluation of the safety in the requirements phase of developing the software. The guideline consists of the requirements engineering for software of KNGR protection systems in chapter 1, the evaluation checklist of software requirements specification in chapter2.3, and the safety evaluation procedure of KNGR software requirements specification in chapter 2.4

  2. Defining System Requirements: a critical assessment of the Niam conceptual design procedure

    Directory of Open Access Journals (Sweden)

    Peta Darke

    1995-05-01

    Full Text Available Requirements definition is a fundamental activity within information systems development. Social and organisational issues are at the centre of many of the problems experienced during the development and implementation of information systems, and these need to be explored during requirements definition. The NIAM Conceptual Schema Design Procedure (CSDP is a method for identifying and describing information requirements using fact types. This paper discusses some limitations of the information requirements definition step of the CSDP which result from its lack of focus on the socio-organisational dimension of information systems development. Four different approaches to exploring the socio-organisational contexts of systems are discussed. It is proposed that one of these, viewpoint development, be incorporated into the NIAM CSDP to provide a means of exploring and understanding a system's socio organisational context and to ensure that contextual information is a major input to the requirements definition process. This results in an enhanced design procedure. Future and current research areas are identified.

  3. Bioequivalence of two misoprostol tablets in healthy Chinese female volunteers: a single-dose, two-period, double crossover study.

    Science.gov (United States)

    Huang, J; Chen, R; Li, R; Wei, C-M; Yuan, G-Y; Liu, X-Y; Wang, B-J; Guo, R-C

    2012-01-01

    To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Demonstrating comparative in vitro bioequivalence for animal drug products through chemistry and manufacturing controls and physicochemical characterization: a proposal.

    Science.gov (United States)

    Martinez, Marilyn N; Fahmy, Raafat

    2015-03-01

    The assessment of in vivo bioequivalence (BE) of nonsystemically absorbed drug products has been a longstanding challenge facing drug manufacturers and regulators of human or animal health products. Typically, in situations where blood level BE studies are not feasible, clinical endpoint BE trials have provided the only option for generating interproduct comparisons. Given the imprecision and logistic challenges associated with these studies, there has been an effort to identify alternative pathways that can reliably ensure the equivalence of product performance and quality. This commentary provides a proposal for an in vitro approach for evaluating the in vivo BE of veterinary drug products that are either nonsystemically absorbed or that act both locally and systemically but where the local site of action is proximal to the absorption window. The assumption underlying this approach is that equivalence in product physicochemical attributes and in vitro product performance translates to equivalence in product in vivo behavior. For sponsors with a right of reference to underlying safety and effectiveness data, this approach could be used to support pre and post-approval changes. When comparing a generic test product to the pioneer (reference listed new animal drug, RLNAD) product, a demonstration of sameness across a battery of in vitro test procedures could be used to confirm that the test and RLNAD products are bioequivalent.

  5. Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

    DEFF Research Database (Denmark)

    Sørensen, Nina Buus; Christiansen, Anders Tolstrup; Kjær, Troels Wesenberg

    2017-01-01

    PURPOSE: The time-dependent effect of anesthetics on the retinal function is debated. We hypothesize that in anesthetized animals there is a time-dependent decline that requires optimized multifocal electroretinogram (mfERG) recording procedures. METHODS: Conventional and four-frame global-flash mf...... by determining the necessary time-of-delay from intraocular injection of a drug to full effect. TRANSLATIONAL RELEVANCE: General anesthesia is a possible source of error in mfERG recordings. Therefore, it is important to investigate the translational relevance of the results to mfERG recordings in children...

  6. Topical bioequivalence of acyclovir creams using dermal microdialysis in pigs: a new model to evaluate bioequivalence for topical formulations.

    Science.gov (United States)

    Wei, Huilin; Wang, Shuqi; Xu, Feng; Xu, Lanfang; Zheng, Jiarun; Chen, Yun

    2012-07-01

    The aim was to evaluate the bioequivalence of topically applied Acyclovir (ACV) creams using dermal microdialysis (DMD) in a pig model. Three ACV creams (3%), ACV1, ACV2 and ACV3, were topically administrated on the dorsum of pigs, and the DMD sampling technique was used to continuously collect microdialysate. The concentration of ACV in microdialysate was measured by HPLC and the concentration-time profiles were used to calculate pharmacokinetic parameters. The results showed that 90% confidence interval (CI) of the ratio of AUC(0-4 h) of ACV2 and ACV3 was between 88.2 and 105.7%, which was within the acceptance range (80-125%). Ninety percent CI of the ratio of C(max) of ACV2 and ACV3 was between 87.4 and 124.4%, which was within the acceptance range (80-125%). These data indicate that ACV2 and ACV3 used in this study were bioequivalent. This study demonstrates that the pig model coupled with DMD sampling can potentially provide a cost-effective strategy to evaluate topical drug delivery and its associated pharmacokinetic studies.

  7. Development of utility generic functional requirements for electronic work packages and computer-based procedures

    Energy Technology Data Exchange (ETDEWEB)

    Oxstrand, Johanna [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-06-01

    The Nuclear Electronic Work Packages - Enterprise Requirements (NEWPER) initiative is a step toward a vision of implementing an eWP framework that includes many types of eWPs. This will enable immediate paper-related cost savings in work management and provide a path to future labor efficiency gains through enhanced integration and process improvement in support of the Nuclear Promise (Nuclear Energy Institute 2016). The NEWPER initiative was organized by the Nuclear Information Technology Strategic Leadership (NITSL) group, which is an organization that brings together leaders from the nuclear utility industry and regulatory agencies to address issues involved with information technology used in nuclear-power utilities. NITSL strives to maintain awareness of industry information technology-related initiatives and events and communicates those events to its membership. NITSL and LWRS Program researchers have been coordinating activities, including joint organization of NEWPER-related meetings and report development. The main goal of the NEWPER initiative was to develop a set of utility generic functional requirements for eWP systems. This set of requirements will support each utility in their process of identifying plant-specific functional and non-functional requirements. The NEWPER initiative has 140 members where the largest group of members consists of 19 commercial U.S. nuclear utilities and eleven of the most prominent vendors of eWP solutions. Through the NEWPER initiative two sets of functional requirements were developed; functional requirements for electronic work packages and functional requirements for computer-based procedures. This paper will describe the development process as well as a summary of the requirements.

  8. Study of the trial subjects’ protection aspects in Phase I clinical trials and bioequivalence studies

    Directory of Open Access Journals (Sweden)

    K. O. Zupanets

    2016-03-01

    Full Text Available Protection of rights, health and well-being of persons who are taking the drug during the trial (trial subjects is one of the basic principles of clinical trials (CT management. Aim. In order to study key aspects of volunteer protection, determine factors that influence these indicators and estimate the importance of ensuring their proper implementation on the clinical site (CS three survey of 135 trial subjects were carried out to evaluate the importance of assessing the impact of factors such as the procedure of signing the informed consent (IC at the CS and testing procedures for HIV / AIDS, hepatitis and others. Assessment of the quality of life of trial subjects as indirect indicator of the quality of clinical trials that ensures the proper protection of their life was the subject of the third survey. Methods and results. The general model of the relationship between the key aspects of the trial subjects protection and the factors which are providing them during the clinical trials of drugs management was substantiated, which included the main aspects of the trial subjects’ protection, protective factors and basic CT management procedures, the impact of the above factors on the possibility of providing protection aspects depends on their implementation quality. It was found that trial subjects’ protection improvement can be achieved during the IC signing process. It is necessary to ensure a higher level of volunteers understanding of the terms that could be used in the IC form. Regarding the procedure of compulsory testing for HIV/AIDS in the course of screening, we can conclude that the majority of the trial subjects believe that this procedure is an additional factor in their health protection and do not consider it as an excessive psychological pressure on them. Conclusion. Assessing the quality of life during the bioequivalence study at the CS makes possible to reach a conclusion on general well-being and satisfaction with those

  9. 78 FR 46965 - Draft Guidance for Industry on Bioequivalence Recommendations for Mesalamine Rectal Suppositories...

    Science.gov (United States)

    2013-08-02

    ...] Draft Guidance for Industry on Bioequivalence Recommendations for Mesalamine Rectal Suppositories... (BE) studies to support abbreviated new drug applications (ANDAs) for mesalamine rectal suppositories... the availability of a draft guidance on mesalamine (Draft Mesalamine Rectal Suppository BE...

  10. 77 FR 10535 - Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations...

    Science.gov (United States)

    2012-02-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369] Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations; Availability... drug products containing the following active ingredients: A Acetaminophen; Caffeine; Dihydrocodeine...

  11. 78 FR 73200 - Draft Guidance for Industry on Bioequivalence Recommendations for Paliperidone Palmitate Extended...

    Science.gov (United States)

    2013-12-05

    ... Paliperidone Palmitate Extended-Release Injectable Suspension; Availability AGENCY: Food and Drug... Paliperidone Palmitate.'' The guidance provides specific recommendations on the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs) for paliperidone palmitate extended-release...

  12. Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

    Science.gov (United States)

    Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

    2015-06-01

    Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

  13. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

    Science.gov (United States)

    Pai, Amy Barton

    2017-11-01

    Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

  14. The basic regulatory considerations and prospects for conducting bioavailability/bioequivalence (BA/BE studies – an overview

    Directory of Open Access Journals (Sweden)

    Shaik Mastan

    2011-03-01

    Full Text Available Shaik Mastan1, Thirunagari Bhavya Latha2, Sathe Ajay11Cytel Statistical Software and Services Pvt Ltd, Pune, Maharashtra, India; 2Business Development, Bioserve Clinical Research Pvt Ltd, Hyderabad, Andhra Pradesh, IndiaAbstract: Bioavailability (BA and bioequivalence (BE studies play a major role in the drug development phase for both new drug products and their generic equivalents, and thus attract considerable attention globally. BE is a strategy to introduce generic equivalents of brand-name drugs (innovator drugs to lower the cost of medication through proper assessment as directed by the international regulatory authorities. There are several approaches to assess BE and each regulatory authority has its own regulations/guidance for conducting BA/BE studies before approving generic products for marketing in their country. Therefore, a thorough understanding is required of these BA/BE concepts and basic regulatory considerations for conducting BA/BE studies. This article briefly reviews the BA/BE concepts, approaches, designs, and various basic regulatory considerations and prospects for conducting BA/BE studies. Keywords: bioavailability, bioequivalence, generic drugs, regulatory authority, pharmacokinetics, pharmacodynamics 

  15. Bioavailability and bioequivalence: focus on physiological factors and variability.

    Science.gov (United States)

    Karalis, Vangelis; Macheras, Panos; Van Peer, Achiel; Shah, Vinod P

    2008-08-01

    This is a summary report of the EUFEPS & COST B25 conference on Bioavailability and Bioequivalence which focused on physiological factors and variability. This conference was held at The Royal Olympic Hotel in the centre of Athens (Greece) during the 1-2 of October in 2007. The issues discussed in the conference involved physiological factors affecting drug absorption, the role of pre-systemic effects on bioavailability (BA), the impact of variability in bioequivalence (BE) studies, and a final closing panel session on unresolved issues in BA/BE regulations. Several important aspects of drug absorption were highlighted. It was presented how the complexity of gastrointestinal (GI) physiology and the site dependent absorption can impact on drug BA. Similarly, the effects of food and formulation were also studied. The second session focused on integrating the complexities of GI into modeling the inter-individual variability of absorption and the prediction of first-pass metabolism from in-vitro data. The necessity to measure metabolites, the value of Biopharmaceutical Classification System (BCS), and the more recently proposed Biopharmaceutical Drug Disposition Classification System (BDDCS) were assessed as well. This session closed with presentations of pharmacokinetic software delegates. In the second day of the conference, the problem of high intra-subject variability in BE studies was analyzed. Study design considerations, the use of multiple-dose studies and the role of statistics in BE were also highlighted. Finally, the current thinking of regulatory authorities (EMEA and US-FDA) was presented. The conference closed with a last session on unresolved issues in the regulatory level.

  16. Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs: current state and future perspectives

    DEFF Research Database (Denmark)

    Holmgaard, R; Nielsen, J B; Benfeldt, E

    2010-01-01

    of instrumentation, calibration and experimental procedures are discussed along with the analytical considerations necessary for successful sampling. Clinical MD studies in the skin are reviewed with emphasis on pharmacokinetic studies of topically applied drugs with or without impairment of skin barrier function...... development, improvement and validation during the last decade and has proved to be a versatile, safe and valuable tool for pharmacokinetic and pharmacodynamic studies. This review gives an overview of the current state and future perspectives of dermal MD sampling. Methodological issues such as choice...... is concluded by the current regulatory point of view. The future perspective includes further expansion and validation of the use of MD in the experimental and clinical setting as well as in the optimization of the method for regulatory purposes, i.e. the commercialization of bioequivalent, generic drug...

  17. Electronic Nose Testing Procedure for the Definition of Minimum Performance Requirements for Environmental Odor Monitoring.

    Science.gov (United States)

    Eusebio, Lidia; Capelli, Laura; Sironi, Selena

    2016-09-21

    Despite initial enthusiasm towards electronic noses and their possible application in different fields, and quite a lot of promising results, several criticalities emerge from most published research studies, and, as a matter of fact, the diffusion of electronic noses in real-life applications is still very limited. In general, a first step towards large-scale-diffusion of an analysis method, is standardization. The aim of this paper is describing the experimental procedure adopted in order to evaluate electronic nose performances, with the final purpose of establishing minimum performance requirements, which is considered to be a first crucial step towards standardization of the specific case of electronic nose application for environmental odor monitoring at receptors. Based on the experimental results of the performance testing of a commercialized electronic nose type with respect to three criteria (i.e., response invariability to variable atmospheric conditions, instrumental detection limit, and odor classification accuracy), it was possible to hypothesize a logic that could be adopted for the definition of minimum performance requirements, according to the idea that these are technologically achievable.

  18. Electronic Nose Testing Procedure for the Definition of Minimum Performance Requirements for Environmental Odor Monitoring

    Directory of Open Access Journals (Sweden)

    Lidia Eusebio

    2016-09-01

    Full Text Available Despite initial enthusiasm towards electronic noses and their possible application in different fields, and quite a lot of promising results, several criticalities emerge from most published research studies, and, as a matter of fact, the diffusion of electronic noses in real-life applications is still very limited. In general, a first step towards large-scale-diffusion of an analysis method, is standardization. The aim of this paper is describing the experimental procedure adopted in order to evaluate electronic nose performances, with the final purpose of establishing minimum performance requirements, which is considered to be a first crucial step towards standardization of the specific case of electronic nose application for environmental odor monitoring at receptors. Based on the experimental results of the performance testing of a commercialized electronic nose type with respect to three criteria (i.e., response invariability to variable atmospheric conditions, instrumental detection limit, and odor classification accuracy, it was possible to hypothesize a logic that could be adopted for the definition of minimum performance requirements, according to the idea that these are technologically achievable.

  19. Survey of international regulatory bioequivalence recommendations for approval of generic topical dermatological drug products.

    Science.gov (United States)

    Braddy, April C; Davit, Barbara M; Stier, Ethan M; Conner, Dale P

    2015-01-01

    The objective of this article is to discuss the similarities and differences in accepted bioequivalence (BE) approaches for generic topical dermatological drug products between international regulatory authorities and organizations. These drug products are locally applied and not intended for systemic absorption. Therefore, the BE approaches which serve as surrogates to establish safety and efficacy for topical dosage forms tend to differ from the traditional solid oral dosage forms. We focused on 15 different international jurisdictions and organizations that currently participate in the International Generic Drug Regulators Pilot Project. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association (EMA), Japan, Mexico, New Zealand, Singapore (a member of the Association of Southeast Asian Nations), South Africa, South Korea, Switzerland, the USA and the World Health Organization (WHO). Upon evaluation, we observed that currently only Canada, the EMA, Japan, and the USA have specific guidance documents for topical drug products. Across all jurisdictions and organizations, the three approaches consistently required are (1) BE studies with clinical endpoints for most topical drug products; (2) in vivo pharmacodynamic studies, in particular the vasoconstrictor assay for topical corticosteroids; and (3) waivers from BE study requirements for topical solutions. Japan, South Africa, the USA, and the WHO are also making strides to accept other BE approaches such as in vivo pharmacokinetic studies for BE assessment, in vivo dermatopharmacokinetic studies and/or BE studies with in vitro endpoints.

  20. Bioequivalence evaluation of two brands of amoxicillin/clavulanic acid 250/125 mg combination tablets in healthy human volunteers: use of replicate design approach.

    Science.gov (United States)

    Idkaidek, Nasir M; Al-Ghazawi, Ahmad; Najib, Naji M

    2004-12-01

    The purpose of this study was to apply a replicate design approach to a bioequivalence study of amoxicillin/clavulanic acid combination following a 250/125 mg oral dose to 23 subjects, and to compare the analysis of individual bioequivalence with average bioequivalence. This was conducted as a 2-treatment 2-sequence 4-period crossover study. Average bioequivalence was shown, while the results from the individual bioequivalence approach had no success in showing bioequivalence. In conclusion, the individual bioequivalence approach is a strong statistical tool to test for intra-subject variances and also subject-by-formulation interaction variance compared with the average bioequivalence approach. copyright (c) 2004 John Wiley & Sons, Ltd.

  1. Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.

    Science.gov (United States)

    Slingerland, Marije; Guchelaar, Henk-Jan; Rosing, Hilde; Scheulen, Max E; van Warmerdam, Laurence J C; Beijnen, Jos H; Gelderblom, Hans

    2013-12-01

    Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties. Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration. Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa. Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia. At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  2. Use of performance curves in estimating number of procedures required to achieve proficiency in coronary angiography

    DEFF Research Database (Denmark)

    Räder, Sune B E W; Jørgensen, Erik; Bech, Bo

    2011-01-01

    .001 for all parameters. To approach the experts' level of DAP and contrast media use, trainees need 394 and 588 procedures, respectively. Performance curves showed large individual differences in the development of competence. Conclusion: On average, trainees needed 300 procedures to reach sufficient level...... needed for trainees to reach recommended reference levels was estimated as 226 and 353, for DAP and use of contrast media, respectively. After 300 procedures, trainees' procedure time, fluoroscopy time, DAP, and contrast media volume were significantly higher compared with experts' performance, P ...Background: Current guidelines in cardiology training programs recommend 100-300 coronary angiography procedures for certification. We aimed to assess the number of procedures needed to reach sufficient proficiency. Methods: Procedure time, fluoroscopy time, dose area product (DAP), and contrast...

  3. Requirements for Control Room Computer-Based Procedures for use in Hybrid Control Rooms

    Energy Technology Data Exchange (ETDEWEB)

    Le Blanc, Katya Lee [Idaho National Lab. (INL), Idaho Falls, ID (United States); Oxstrand, Johanna Helene [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey Clark [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-05-01

    Many plants in the U.S. are currently undergoing control room modernization. The main drivers for modernization are the aging and obsolescence of existing equipment, which typically results in a like-for-like replacement of analogue equipment with digital systems. However, the modernization efforts present an opportunity to employ advanced technology that would not only extend the life, but enhance the efficiency and cost competitiveness of nuclear power. Computer-based procedures (CBPs) are one example of near-term advanced technology that may provide enhanced efficiencies above and beyond like for like replacements of analog systems. Researchers in the LWRS program are investigating the benefits of advanced technologies such as CBPs, with the goal of assisting utilities in decision making during modernization projects. This report will describe the existing research on CBPs, discuss the unique issues related to using CBPs in hybrid control rooms (i.e., partially modernized analog control rooms), and define the requirements of CBPs for hybrid control rooms.

  4. Bioequivalence study of two enalapril maleate tablet formulations in healthy male volunteers. Pharmacokinetic versus pharmacodynamic approach.

    Science.gov (United States)

    Ribeiro, W; Muscará, M N; Martins, A R; Moreno, H; Mendes, G B; de Nucci, G

    1996-01-01

    Two different conventional release enalapril maleate tablet formulations were evaluated for their relative bioavailability (Eupressin tablets 10 mg, Biosintética as the test formulation vs Renitec tablets 10 mg Merck Sharp & Dhome, as the reference formulation). A single 20 mg oral dose of each preparation was administered to 18 healthy male adult volunteers and their bioequivalence was assessed by comparing the serum enalaprilat and total enalapril (enalaprilat plus enalapril maleate) concentration-time curves. Angiotensin converting enzyme (ACE) activity was also quantified in each serum sample. The pharmacokinetic parameters obtained for each formation were the area under the time-concentration curve from 0 to 24 h (AUC[0-24]), maximum concentration Cmax and the time at which it occurred (tmax). When serum enalaprilat concentration-time curves were employed to assess bioequivalence, the formulations were bioequivalent in the extent but not in the rate of absorption. However, no difference in either the extent or the rate of absorption were observed when serum total enalapril vs time curves were analysed. ACE activity-time curves were similar for both formulations and showed that ACE was 90% inhibited for 3-5 h after enalapril administration, and till approximately 50% after 24 h. At that time, circulating enalaprilat and total enalapril levels were less than the tenth of Cmax. The results show that complete bioequivalence of the two formulations can be concluded from serum total enalapril concentration data, and that serum ACE activity is not a suitable pharmacodynamic variable for assessing bioequivalence.

  5. Topical safety and vasoconstrictive assay-based bioequivalence of a new reformulated mometasone cream.

    Science.gov (United States)

    Krishna, Rajesh; Horowitz, Ann; Larson, Patrick; Bolognese, James; Marcantonio, Eugene E

    2017-07-01

    A new improved mometasone furoate (Elocon™) cream with an emulsification system that produces a stable emulsion has been developed. In order to register the product in various markets, it was essential to ensure the cream was topically well tolerated and that it was bioequivalent to the reference product. Phase I clinical studies were performed to assess the local safety and tolerability upon multiple dosing of this new cream as well as to assess the single-dose bioequivalence relative to the marketed product. Bioequivalence was assessed using a vasoconstrictive assay (VCA) after a dose-duration pilot study was completed with the marketed Elocon cream. The new mometasone cream and its vehicle were nonirritating in healthy subjects during 21-day patch application (MCII cream in various markets.

  6. 75 FR 31334 - Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's “Required Use...

    Science.gov (United States)

    2010-06-03

    ... by those in a position to refer settlement business (such as builders, real estate agents, and...-A178 Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's ``Required Use... referral fees, kickbacks, and unearned fees for real estate settlement services.\\1\\ \\1\\ In July 2008...

  7. 26 CFR 1.852-9 - Special procedural requirements applicable to designation under section 852(b)(3)(D).

    Science.gov (United States)

    2010-04-01

    ... notice by the Internal Revenue Service that the regulated investment company has failed to comply with... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Special procedural requirements applicable to designation under section 852(b)(3)(D). 1.852-9 Section 1.852-9 Internal Revenue INTERNAL REVENUE SERVICE...

  8. Risk and safety requirements for diagnostic and therapeutic procedures in allergology

    DEFF Research Database (Denmark)

    Kowalski, Marek L; Ansotegui, Ignacio; Aberer, Werner

    2016-01-01

    One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin...

  9. 49 CFR 192.711 - Transmission lines: General requirements for repair procedures.

    Science.gov (United States)

    2010-10-01

    ... time of discovery. (b) Permanent repairs. An operator must make permanent repairs on its pipeline... repair procedures. 192.711 Section 192.711 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED...

  10. [Radiation protection in medical research : Licensing requirement for the use of radiation and advice for the application procedure].

    Science.gov (United States)

    Minkov, V; Klammer, H; Brix, G

    2017-07-01

    In Germany, persons who are to be exposed to radiation for medical research purposes are protected by a licensing requirement. However, there are considerable uncertainties on the part of the applicants as to whether licensing by the competent Federal Office for Radiation Protection is necessary, and regarding the choice of application procedure. The article provides explanatory notes and practical assistance for applicants and an outlook on the forthcoming new regulations concerning the law on radiation protection of persons in the field of medical research. Questions and typical mistakes in the application process were identified and evaluated. The qualified physicians involved in a study are responsible for deciding whether a license is required for the intended application of radiation. The decision can be guided by answering the key question whether the study participants would undergo the same exposures regarding type and extent if they had not taken part in the study. When physicians are still unsure about their decision, they can seek the advisory service provided by the professional medical societies. Certain groups of people are particularly protected through the prohibition or restriction of radiation exposure. A simplified licensing procedure is used for a proportion of diagnostic procedures involving radiation when all related requirements are met; otherwise, the regular licensing procedure should be used. The new radiation protection law, which will enter into force on the 31st of december 2018, provides a notification procedure in addition to deadlines for both the notification and the licensing procedures. In the article, the authors consider how eligible studies involving applications of radiation that are legally not admissible at present may be feasible in the future, while still ensuring a high protection level for study participants.

  11. 78 FR 66745 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

    Science.gov (United States)

    2013-11-06

    ... provide product-specific guidance on the design of BE studies to support abbreviated new drug applications... industry entitled ``Bioequivalence Recommendations for Specific Products,'' which explained the process...,'' which explained the process that would be used to make product-specific BE recommendations available to...

  12. 77 FR 56851 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

    Science.gov (United States)

    2012-09-14

    ... provide product-specific guidance on the design of BE studies to support abbreviated new drug applications... industry entitled ``Bioequivalence Recommendations for Specific Products,'' which explained the process...,'' which explained the process that would be used to make product-specific BE recommendations available to...

  13. 75 FR 33311 - Guidance for Industry on Bioequivalence Recommendations for Specific Products; Availability

    Science.gov (United States)

    2010-06-11

    ... describes a new process for making available recommendations on how to design product- specific... guidance describes a new process for making available recommendations on how to design product-specific BE... guidance on how to design product-specific bioequivalence studies to support ANDAs. It does not create or...

  14. 77 FR 16842 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

    Science.gov (United States)

    2012-03-22

    ... provide product-specific guidance on the design of BE studies to support abbreviated new drug applications... industry entitled ``Bioequivalence Recommendations for Specific Products,'' which explained the process...,'' which explained the process that would be used to make product-specific BE recommendations available to...

  15. 78 FR 52777 - Draft Guidance for Industry on Bioequivalence Recommendations for Risperidone Injection...

    Science.gov (United States)

    2013-08-26

    ... on Bioequivalence Recommendations for Risperidone Injection; Availability AGENCY: Food and Drug... availability of a revised draft guidance for industry entitled ``Draft Guidance on Risperidone.'' The guidance... drug applications (ANDAs) for risperidone injection. DATES: Although you can comment on any guidance at...

  16. Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel

    DEFF Research Database (Denmark)

    Tettey-Amlalo, Ralph Nii Okai; Kanfer, Isadore; Skinner, Michael F

    2008-01-01

    The purpose was to investigate dermal microdialysis (DMD) for the assessment of the bioavailability of a ketoprofen topical gel formulation and to evaluate this technique as a tool for the determination of bioequivalence. Four microdialysis probes were inserted into the dermis on the volar aspect...

  17. Assessment of topical bioequivalence using dermal microdialysis and tape stripping methods.

    Science.gov (United States)

    Incecayir, Tuba; Agabeyoglu, Ilbeyi; Derici, Ulver; Sindel, Sukru

    2011-09-01

    To assess the bioequivalence of two commercial topical formulations of oxytetracycline HCl by tape stripping and microdialysis in healthy volunteers. Tape stripping study was conducted on 12 healthy volunteers. After a 30-minute application of the formulations, adhesive tapes were used to sample stratum corneum at 0.25, 0.5, 1, 1.5, 2, 3, 4 hr. Ten of these volunteers were included in the microdialysis study with a period of 4 weeks between the experiments. Microdialysis probes were inserted into the dermis of the forearm. Following the application of the test and reference simultaneously, dialysates were collected in 30-minute sampling intervals up to 4 hr. Pharmacokinetic evaluation by microdialysis yielded that the test could not be said to be bioequivalent to the reference at 90% CI. The intersubject variability of oxytetracycline content in stratum corneum was moderate when it was compared to the dermal levels. The test was found to be bioequivalent to reference according to the dermatopharmacokinetic evaluation by tape stripping. No significant correlations were found between microdialysis and tape stripping methods as regarding the topical bioequivalence of oxytetracycline HCl formulations.

  18. Determination of bioequivalence of lomefloxacin tablets using urinary excretion data.

    Science.gov (United States)

    Shah, Shailesh A; Rathod, Ishwarsinh S; Savale, Shrinivas S; Patel, Dharmesh B

    2002-11-07

    The present study describes development of a sensitive and simple HPTLC method for estimation of lomefloxacin (LMF) in human urine. The drug was extracted using chloroform after adjusting the pH of urine to 7.0. Chloroform extract was spotted on silica gel 60 F(254) TLC plate and was developed in a mixture of n-butanol-methanol-ethyl acetate-6 M ammonia (4:2:3:2, v/v/v/v) as the mobile phase and scanned at 290 nm. The peak for LMF resolved at R(F) of 0.40+/-0.02. The method was validated in terms of linearity (50-600 microgram/ml), precision, specificity and accuracy. The limit of detection and limit of quantification for LMF in urine were found to be 20 and 50 microgram/ml, respectively. The average recovery of LMF from urine was 91.93%. The proposed method was applied to generate urinary excretion data for LMF after administration of two market LMF tablet formulations (400 mg, Formulation R and Formulation T) to six healthy human volunteers in a two-treatment, open, crossover design. Various pharmacokinetic parameters like peak excretion rate ((dAU/dt)(max)), time for peak excretion rate (t(max)), AUC(0-48), AUC(0- infinity ), cumulative amount and % cumulative amount of LMF excreted, elimination half-life (t(1/2)), terminal elimination rate constant (k(el)) and overall elimination rate constant (K), were calculated for both the formulations. The average cumulative amounts of LMF excreted in urine after administration of Formulation R and Formulation T were found to be 321.60 mg (80.40% of dose) and 296.51 mg (74.13% of dose), respectively. The urinary excretion profiles of LMF upto 48 h for both the formulations were found to be similar. Statistical comparison (90% confidence intervals of ratio) of various pharmacokinetic parameters of Formulation T with that of Formulation R revealed that Formulation T is bioequivalent with Formulation R.

  19. A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers

    Directory of Open Access Journals (Sweden)

    Suyan Tian

    2016-01-01

    Full Text Available In order to test if two chemically or pharmaceutically equivalent products have the same efficacy and/or toxicity, a bioequivalence (BE study is conducted. The 80%/125% rule is the most commonly used criteria for BE and states that BE cannot be claimed unless the 90% CIs for the ratio of selected pharmacokinetics (PK parameters of the tested to the reference drug are within 0.8 to 1.25. Considering that estimates of these PK parameters are derived from the concentration-versus-time curves, a direct comparison between these curves motivates an alternative and more flexible approach to test BE. Here, we propose to frame the BE test in terms of an equivalence of concentration-versus-time curves which are constructed using local polynomial smoother (LPS. A metric is presented to quantify the distance between the curves and its 90% CIs are calculated via bootstrapping. Then, we applied the proposed procedures to data from an animal study and found that BE between a generic drug and its brand name cannot be concluded, which was consistent with the results by applying the 80%/125% rule. However, the proposed procedure has the advantage of testing only on a single metric, instead of all PK parameters.

  20. Requirements for Computer Based-Procedures for Nuclear Power Plant Field Operators Results from a Qualitative Study

    Energy Technology Data Exchange (ETDEWEB)

    Katya Le Blanc; Johanna Oxstrand

    2012-05-01

    Although computer-based procedures (CBPs) have been investigated as a way to enhance operator performance on procedural tasks in the nuclear industry for almost thirty years, they are not currently widely deployed at United States utilities. One of the barriers to the wide scale deployment of CBPs is the lack of operational experience with CBPs that could serve as a sound basis for justifying the use of CBPs for nuclear utilities. Utilities are hesitant to adopt CBPs because of concern over potential costs of implementation, and concern over regulatory approval. Regulators require a sound technical basis for the use of any procedure at the utilities; without operating experience to support the use CBPs, it is difficult to establish such a technical basis. In an effort to begin the process of developing a technical basis for CBPs, researchers at Idaho National Laboratory are partnering with industry to explore CBPs with the objective of defining requirements for CBPs and developing an industry-wide vision and path forward for the use of CBPs. This paper describes the results from a qualitative study aimed at defining requirements for CBPs to be used by field operators and maintenance technicians.

  1. Requirements for Computer Based-Procedures for Nuclear Power Plant Field Operators. Results from a Qualitative Study

    International Nuclear Information System (INIS)

    Le Blanc, Katya; Oxstrand, J.H.; Waicosky, T.

    2012-01-01

    Although computer-based procedures (CBPs) have been investigated as a way to enhance operator performance on procedural tasks in the nuclear industry for almost thirty years, they are not currently widely deployed at United States utilities. One of the barriers to the wide scale deployment of CBPs is the lack of operational experience with CBPs that could serve as a sound basis for justifying the use of CBPs for nuclear utilities. Utilities are hesitant to adopt CBPs because of concern over potential costs of implementation, and concern over regulatory approval. Regulators require a sound technical basis for the use of any procedure at the utilities; without operating experience to support the use CBPs, it is difficult to establish such a technical basis. In an effort to begin the process of developing a technical basis for CBPs, researchers at Idaho National Laboratory are partnering with industry to explore CBPs with the objective of defining requirements for CBPs and developing an industry-wide vision and path forward for the use of CBPs. This paper describes the results from a qualitative study aimed at defining requirements for CBPs to be used by field operators and maintenance technicians. (author)

  2. Procedure 5 Quality Assurance Requirements For Vapor Phase Mercury Continuous Emissions Monitoring Systems And Sorbent Trap Monitoring Systems Used For Compliance Determination At Stationary Sources

    Science.gov (United States)

    Promulgated quality assurance Procedure 5 Quality Assurance Requirements For Vapor Phase Mercury Continuous Emissions Monitoring Systems And Sorbent Trap Monitoring Systems Used For Compliance Determination At Stationary Sources

  3. Remote maintenance systems requirements are being developed to provide design guidelines for machine components, to define maintenance interfaces, and to quantify maintenance equipment and procedures needed

    International Nuclear Information System (INIS)

    Spampinato, P.T.; Tabor, M.A.

    1988-01-01

    Remote maintenance systems requirements are being developed to provide design guidelines for machine components, to define maintenance interfaces, and to quantify maintenance equipment and procedures needed

  4. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Science.gov (United States)

    2010-04-01

    ... requirements under HUD building products certification program for solid fuel type room heaters and fireplace... type room heaters and fireplace stoves. (a) Applicable standards. Solid fuel type room heaters and fireplace stoves certified under the HUD Building Products Certification Program shall be designed...

  5. Restrictive Behaviour Management Procedures with People with Intellectual Disabilities Who Require Dental Treatment

    Science.gov (United States)

    Newton, J. T.

    2009-01-01

    Background: Dental disease is more common among people with intellectual disabilities than in the general population. Improvements in oral health require individuals to engage in daily oral hygiene and regular visits to a dental practitioner; both may be challenging for the individual with intellectual impairment. Materials and Methods: A review…

  6. 36 CFR 251.54 - Proposal and application requirements and procedures.

    Science.gov (United States)

    2010-07-01

    ... radioactive or other hazardous substances. (2) Results of initial screening. Any proposed use other than a... lands, the proponent is required to contact the Forest Service office(s) responsible for the management... with the State Office, Bureau of Land Management, pursuant to regulations at 43 CFR part 2882. (c...

  7. 48 CFR 8.405-2 - Ordering procedures for services requiring a statement of work.

    Science.gov (United States)

    2010-10-01

    ... clearances, travel, special knowledge). To the maximum extent practicable, agency requirements shall be... that contractors submit firm-fixed prices to perform the services identified in the statement of work... price reductions. (4) The ordering activity shall provide the RFQ (including the statement of work and...

  8. 77 FR 44235 - Forms and Procedures for Submitting Compliance Reports: Requirements Pertaining to Reformulated...

    Science.gov (United States)

    2012-07-27

    ... Pending; DSF0900: Motor Vehicle Diesel Fuel Sulfur Pre-Compliance Report, OMB Control Number 2060-0308... information; Diesel fuel; Fuel additives; Gasoline; Imports; Motor vehicle pollution; Reporting and... requirements pertaining to reformulated gasoline, anti-dumping, gasoline sulfur, ultra-low sulfur diesel...

  9. 75 FR 76254 - Official Performance and Procedural Requirements for Grain Weighing Equipment and Related Grain...

    Science.gov (United States)

    2010-12-08

    ...: Section 1.10 General Code Section 2.20 Scales Section 2.22 Automatic Bulk Weighing Systems Section 2.23... Weighing Handbook, the General Code, the Scales Code, the Automatic Bulk Weighing Systems Code, and the... requirements are not incorporated by reference: Scales (2.20) S.1.8. Computing Scales S.1.8.2. Money-Value...

  10. Peculiarities of practical application of offset of counter homogeneous requirements in the liquidation procedure

    OpenAIRE

    Чубар, Тетяна

    2017-01-01

    The article is devoted to the peculiarities of practical application of uniform admission counter claims in the liquidation proceedings. The author of the essence, main content and implications of the liquidation proceedings in respect of an insolvent debtor. Analyzed the sequence of creditors' claims based on the principle of proportionality satisfaction of one stage and the full satisfaction of the previous turn.The analysis of the category «redeemed requirements» and explored grounds for t...

  11. Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

    Science.gov (United States)

    Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

    2017-09-01

    Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

  12. A simple procedure eliminating multiple optimization steps required in developing multiplex PCR reactions

    Energy Technology Data Exchange (ETDEWEB)

    Grondin, V.; Roskey, M.; Klinger, K.; Shuber, T. [Integrated Genetics, Framingham, MA (United States)

    1994-09-01

    The PCR technique is one of the most powerful tools in modern molecular genetics and has achieved widespread use in the analysis of genetic diseases. Typically, a region of interest is amplified from genomic DNA or cDNA and examined by various methods of analysis for mutations or polymorphisms. In cases of small genes and transcripts, amplification of single, small regions of DNA are sufficient for analysis. However, when analyzing large genes and transcripts, multiple PCRs may be required to identify the specific mutation or polymorphism of interest. Ever since it has been shown that PCR could simultaneously amplify multiple loci in the human dystrophin gene, multiplex PCR has been established as a general technique. The properities of multiplex PCR make it a useful tool and preferable to simultaneous uniplex PCR in many instances. However, the steps for developing a multiplex PCR can be laborious, with significant difficulty in achieving equimolar amounts of several different amplicons. We have developed a simple method of primer design that has enabled us to eliminate a number of the standard optimization steps required in developing a multiplex PCR. Sequence-specific oligonucleotide pairs were synthesized for the simultaneous amplification of multiple exons within the CFTR gene. A common non-complementary 20 nucleotide sequence was attached to each primer, thus creating a mixture of primer pairs all containing a universal primer sequence. Multiplex PCR reactions were carried out containing target DNA, a mixture of several chimeric primer pairs and primers complementary to only the universal portion of the chimeric primers. Following optimization of conditions for the universal primer, limited optimization was needed for successful multiplex PCR. In contrast, significant optimization of the PCR conditions were needed when pairs of sequence specific primers were used together without the universal sequence.

  13. The significance of pharmacodynamic measurements in the assessment of bioavailability and bioequivalence of psychotropic drugs using CEEG and dynamic brain mapping.

    Science.gov (United States)

    Itil, T M; Itil, K Z

    1986-09-01

    There are a variety of problems in evaluating the bioavailability of psychotropic drugs. Psychotropics have many metabolites; there are discrepancies between peripheral plasma levels and therapeutic effects, and psychotropics must penetrate the blood-brain barrier to have an effect on their target organ. Therefore, "classical" pharmacokinetic evaluation may not be sufficient to determine the bioavailability and bioequivalence of these drugs. Additional and more precise information may be obtained by adding pharmacodynamic procedures to these evaluations. Quantitative pharmaco-EEG (QPEEG), which uses the computer-analyzed electroencephalogram (CEEG), may be the method of choice for determining the pharmacodynamic profiles of psychotropic drugs at the central nervous system (CNS) level. The difficulties in evaluating the bioavailability of psychotropics, as well as the results of several studies that confirm the significance of CEEG as a pharmacodynamic measure, are discussed.

  14. Complete dataset for 2-treatment, 2-sequence, 2-period efavirenz bioequivalence study conducted with nightly dosing

    Directory of Open Access Journals (Sweden)

    Manuel Ibarra

    2016-06-01

    Full Text Available The efavirenz pharmacokinetic raw data presented in this article was obtained in an average bioequivalence study between a local brand and Stocrin (Merck Sharp & Dohme, purchased from Australia, batch H009175, expiration date November 2013. Dose was administered at night (9:00 p.m. two hours after food intake. Fourteen healthy subjects, 8 women and 6 men, completed the study. For each subject, 15 data points until 96 h post-administration are included. Subject demographic characteristics and sequences of administration are provided along with individual pharmacokinetic profiles of efavirenz obtained for both formulations after a single oral dose of 600 mg. This data provides information in support of the research article “Sex-by-formulation interaction assessed through a bioequivalence study of efavirenz tablets” [1].

  15. Constraints on LISA Pathfinder's Self-Gravity: Design Requirements, Estimates and Testing Procedures

    Science.gov (United States)

    Armano, M.; Audley, H.; Auger, G.; Baird, J.; Binetruy, P.; Born, M.; Bortoluzzi, M.; Brandt, Nico; Bursi, Alessandro; Slutsky. J.; hide

    2016-01-01

    LISA Pathfinder satellite was launched on 3 December 2015 toward the Sun Earth first Lagrangian point (L1) where the LISA Technology Package (LTP), which is the main science payload, will be tested. LTP achieves measurements of differential acceleration of free-falling test masses (TMs) with sensitivity below 3 x 10(exp -14) m s(exp -2) Hz(exp - 1/2) within the 130 mHz frequency band in one dimension. The spacecraft itself is responsible for the dominant differential gravitational field acting on the two TMs. Such a force interaction could contribute a significant amount of noise and thus threaten the achievement of the targeted free-fall level. We prevented this by balancing the gravitational forces to the sub nm s(exp -2) level, guided by a protocol based on measurements of the position and the mass of all parts that constitute the satellite, via finite element calculation tool estimates. In this paper, we will introduce the gravitational balance requirements and design, and then discuss our predictions for the balance that will be achieved in flight.

  16. In vitro bioequivalence study of nine brands of artesunate tablets marketed in Nigeria.

    Science.gov (United States)

    Esimone, C O; Okoye, F B C; Onah, B U; Nworu, C S; Omeje, E O

    2008-03-01

    The availability of numerous brands of artesunate in our drug market today places clinicians and pharmacists in a difficult situation of choice of a suitable brand or the possibility of alternative use. The aim of the present study was to predict the bioequivalence of nine brands of artesunate tablets marketed in Nigeria using in vitro tests. The in vitro dissolution study was carried out on the nine brands of artesunate tablets using the basket method according to US Pharmacopoeia (USP) guidelines. Other general quality assessment tests like hardness and disintegration time were also determined. All the brands tested passed the British Pharmacopoeia (BP) standard for disintegration time. Only AT2, AT4, AT6 and AT9 passed the standard for hardness. There were significant differences in the dissolution profiles of the nine brands. All the brands except AT1, however, released >70% of artesunate within 30 min. Four of the brands AT5, AT6, AT7 and AT8 exhibited >90% dissolution in AT9 (innovator brand) have calculated similarity factors of 23.8, 59.8, 50, 54.8 and 100. Based on the in vitro tests, AT5, AT6, AT7 and AT8 are considered bioequivalent and interchangeable, while AT2, AT3 and AT4 are considered bioequivalent and interchangeable with the innovator brand (AT9). AT1 has very low dissolution rate, which will likely result in poor bioavailability. The results show the need for constant monitoring of new brands of artesunate introduced into the drug market to ascertain bioequivalence and conformity with pharmacopoeia standards.

  17. From drug delivery systems to drug release, dissolution, IVIVC, BCS, BDDCS, bioequivalence and biowaivers.

    Science.gov (United States)

    Karalis, Vangelis; Magklara, Eleni; Shah, Vinod P; Macheras, Panos

    2010-09-01

    This is a summary report of the conference on drug absorption and bioequivalence issues held in Titania Hotel in Athens (Greece) from the 28(th) to the 30(th) of May 2009. The conference included presentations which were mainly divided into three sections. The first section focused on modern drug delivery systems such as polymer nanotechnology, cell immobilization techniques to deliver drugs into the brain, nanosized liposomes used in drug eluting stents, encapsulation of drug implants in biocompatible polymers, and application of differential scanning calorimetry as a tool to study liposomal stability. The importance of drug release and dissolution were also discussed by placing special emphasis on camptothecins and oral prolonged release formulations. The complexity of the luminal environment and the value of dissolution in lyophilized products were also highlighted. The second session of the conference included presentations on the Biopharmaceutics Classification Scheme (BCS), the Biopharmaceutics Drug Disposition Classification System (BDDCS), and the role of transporters in the classification of drugs. The current status of biowaivers and a modern view on non-linear in vitro-in vivo (IVIVC) correlations were also addressed. Finally, this section ended with a special topic on biorelevant dissolution media and methods. The third day of the conference was dedicated to bioequivalence. Emphasis was placed on high within-subject variability and its impact on study design. Two unresolved issues of bioequivalence were also discussed: the use of generic antiepileptic drugs and the role of metabolites in bioequivalence assessment. Finally, the conference closed with a presentation of the current regulatory status of WHO and EMEA.

  18. Bioequivalence of eslicarbazepine acetate from two different sources of its active product ingredient in healthy subjects.

    Science.gov (United States)

    Falcão, Amílcar; Lima, Ricardo; Sousa, Rui; Nunes, Teresa; Soares-da-Silva, Patrício

    2013-06-01

    To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions--either a single oral tablet of MF or a single oral tablet of TBM--separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90% confidence intervals (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were within the predetermined range of 80-125%. Test/reference GMR (90% CI) for the Cmax and AUC was respectively 100% (94-109%) and 96% (94-98%) following 400 mg ESL and 100% (95-105%) and 100% (97-103%) following 800 mg ESL. Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix® formulation according to the regulatory definition of bioequivalence.

  19. Development of novel bepotastine salicylate salt bioequivalent to the commercial bepotastine besilate in beagle dogs.

    Science.gov (United States)

    Cho, Kwan Hyung; Choi, Han-Gon

    2013-06-01

    To develop a novel salt form of bepotastine with bioequivalent to the commericial bepostastine besilate, bepostastine salicylate was prepared and its physicochemical properties were investigated. Furthermore, the bepotastine salicylate-loaded tablet was prepared by the wet granulation method, and the dissolution and bioavailability in beagle dogs were evaluated compared to the bepotastine besilate-loaded commercial product. Bepotastine salicylate improved the solubility of bepotastine, and the extent of solubility improvement by salicylate form was similar to that by besilate form. However, this novel salt exhibited negligible hygroscopicity similar to besilate form, and showed slightly higher melting point than besilate form. It was stable in various pH solutions. Furthermore, the bepotastine salicylate-loaded tablet composed of bepotastine salicylate, microcrystalline cellulose, D-mannitol, povidone, sodium starch glycolate and sodium stearyl fumarate at the weight ratio of 9.63/60.97/38/3.6/6/1.8 showed similar dissolution to the bepotastine besilate-loaded commercial product in water, pH 1.2, pH 4.0 and pH 6.8 and was bioequivalent to the commercial product in beagle dogs. Thus, this bepotastine salicylate-loaded tablet would be a promising candidate with bioequivalence to the bepotastine besilate-loaded commercial product.

  20. Bioequivalence Study of Pantoprazole Sodium-HPBCD and Conventional Pantoprazole Sodium Enteric-Coated Tablet Formulations

    Science.gov (United States)

    Kamdi, Sandesh P.; Palkar, Prashant J.

    2013-01-01

    The objective of this study was to investigate the bioequivalence of two formulations of 40 mg pantoprazole sodium enteric-coated tablets: Tripepsa as the test and Pantocid as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 1-month washout period in 25 healthy Indian volunteers. After drug administration, serial blood samples were collected over a period of 30 hours. Plasma pantoprazole concentrations were measured by high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0−∞ and C max were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0−∞ and C max values of the test product over those of the reference product were 90.21 (83.69–97.24) and 108.68 (100.21–117.86), respectively (within the bioequivalence range of 80–125%). On the basis of pharmacokinetic parameters including AUC0−∞, AUC0−t, and C max values, both the formulations were bioequivalent. PMID:23476803

  1. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

  2. Bioequivalence study of two formulations of candesartan cilexetil tablet in healthy subjects under fasting conditions

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2013-08-01

    Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Danang Agung Yunaidi,2 Ronal Simanjuntak,2 Iwan Dwi Santoso,2 Liana W Susanto1 1Dexa Laboratories of Biomolecular Sciences (DLBS, Cikarang, Indonesia; 2Bioavailability and Bioequivalence Laboratory, PT Equilab International, Jakarta, Indonesia Introduction: The present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations. Materials and methods: This study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7, using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week, a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax, time to achieve the Cmax, and the elimination half-life. Results: The geometric mean ratios (90% confidence interval of the test drug/reference drug for candesartan were 100.92% (92.15%–110.52% for the AUC from 0 hours to 24 hours, 100.24% (92.24%–108.95% for the AUC from time zero to infinity, and 106.71% (93.20%–122.18% for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study. Conclusion: It was concluded that the two candesartan tablet

  3. Juvenile osteochondritis dissecans in the lateral femoral condyle requiring osteochondral autograft as a revision procedure: a case report.

    Science.gov (United States)

    Kanto, Ryo; Nakayama, Hiroshi; Iseki, Tomoya; Yoshiya, Shinichi

    2016-01-14

    The optimal treatment option for osteochondritis dissecans of the knee is still controversial. We report the case of a boy who developed osteochondritis dissecans in the lateral femoral condyles of his bilateral knees requiring repeat surgical procedures. There has been no literature reporting juvenile osteochondritis dissecans of bilateral knees requiring repeat surgical procedures. A 6-year-old Japanese boy presented with pain in his bilateral knees. Although conservative treatment with prohibition of sports activities was continued for 6 months, healing could not be attained. Conservative treatment consisting of prohibition of sports activities that included running and jumping and use of a brace with a locking mechanism at full extension was applied. He was instructed to walk with the brace. Since his lateral femoral osteochondritis dissecans lesion was located at the contact area during flexion, weight bearing with the use of the brace could effectively unload the lesion. Surgery was subsequently conducted on his left knee which had a more advanced stage lesion. Transchondral drilling was performed because the articular surface maintained its smooth continuity. At 9 months after the surgery, no appreciable healing was observed in the follow-up radiographs. Moreover, during the postoperative time course, lesions suggestive of osteochondritis dissecans in his contralateral right knee had become more evident. Based on the diagnosis of delayed union of bilateral osteochondritis dissecans lesions, a second surgery was attempted. The preceding arthroscopic observation of his left knee showed preserved surface continuity with softening and suspected partial detachment. Considering the delayed healing process observed in this patient, autogenous cylindrical osteochondral graft transplantation (8 mm in diameter) was performed as a revision procedure, while transchondral drilling was performed for the stable osteochondritis dissecans lesion in his right knee

  4. Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

    Energy Technology Data Exchange (ETDEWEB)

    Szebeni, Janos, E-mail: jszebeni2@gmail.com [Nanomedicine Research and Education Center, Semmelweis University, Budapest & SeroScience Ltd, Budapest (Hungary); Storm, Gert [Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht (Netherlands)

    2015-12-18

    Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

  5. When Bioequivalence in Healthy Volunteers May not Translate to Bioequivalence in Patients: Differential Effects of Increased Gastric pH on the Pharmacokinetics of Levothyroxine Capsules and Tablets.

    Science.gov (United States)

    Seng Yue, Corinne; Benvenga, Salvatore; Scarsi, Claudia; Loprete, Luca; Ducharme, Murray P

    2015-01-01

    Clinical studies have suggested that proton pump inhibitors may decrease levothyroxine absorption and an in vitro study suggested that the effect of pH on dissolution may differ with formulation. To determine the impact of formulation on the pharmacokinetics of levothyroxine in altered gastric pH conditions, this study compared the pharmacokinetics of levothyroxine capsules and tablets, two formulations deemed bioequivalent in healthy volunteers under fasting conditions, when taken with or without esomeprazole. Two clinical studies were conducted in healthy volunteers given single dose levothyroxine (600 mg) with a 45-day washout period. In Study 1 (parallel-design/two-way crossover), 16 subjects received either levothyroxine capsules or tablets, each group with or without prior administration of intravenous esomeprazole (maximum dose of 80 mg). In Study 2 (two-way crossover), 16 subjects received both capsules or tablets after intravenous esomeprazole. Blood samples were collected pre-dose and up to 24 hours post-dose. Baseline-adjusted pharmacokinetic parameters were calculated: Cmax (maximal concentration), Tmax (time to Cmax), AUC0-t (area under the concentration-time curve from 0 to the last detectable concentration), AUC0-6 and AUC0-12 (areas under the curve from 0 to 6 and 12 hours, respectively). Analyses of variance were conducted to compare ln-transformed Cmax and AUC. Non-parametric Tmax analyses were done. In Study 1, esomeprazole caused a greater decrease in overall levothyroxine exposure of tablets vs. capsules (13% vs 6% for Cmax, 18% vs. 14% for AUC(0-6), 17% vs. 5% for AUC(0-12) and 10% vs. 8% for AUC(0-t)). In Study 2 esomeprazole administration resulted in a 16% smaller levothyroxine exposure with tablets vs. capsules. No statistically significant differences in Tmax were found. Although both formulations are considered "bioequivalent" in healthy volunteers, they may not necessarily be bioequivalent in patients with impaired gastric pH conditions

  6. 49 CFR 40.209 - What procedural problems do not result in the cancellation of a test and do not require correction?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What procedural problems do not result in the cancellation of a test and do not require correction? 40.209 Section 40.209 Transportation Office of the... Problems in Drug Tests § 40.209 What procedural problems do not result in the cancellation of a test and do...

  7. Integration of in vitro biorelevant dissolution and in silico PBPK model of carvedilol to predict bioequivalence of oral drug products.

    Science.gov (United States)

    Ibarra, Manuel; Valiante, Cristian; Sopeña, Patricia; Schiavo, Alejandra; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

    2018-06-15

    Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment. By coupling in vitro biorelevant dissolution testing in USP-4 Apparatus (flow-through cell) with physiologically-based pharmacokinetic (PBPK) modeling in PK-Sim® software (Bayer, Germany), the performance of seven similar products of carvedilol tablets containing 25 mg available in the Uruguayan market were compared with the brand-name drug Dilatrend®. In silico simulations for Dilatrend® were compared with published results of bioequivalence studies performed in fasting conditions allowing model development through a learning and confirming process. Single-dose pharmacokinetic profiles were then simulated for the brand-name drug and two similar drug products selected according to in vitro observations, in a virtual Caucasian population of 1000 subjects (50% male, aged between 18 and 50 years with standard body-weights). Population bioequivalence ratios were estimated revealing that in vitro differences in drug release would have a major impact in carvedilol maximum plasma concentration, leading to a non-bioequivalence outcome. Predictions support the need to perform in vivo bioequivalence for these products of extensive use. Application of the in vitro-in silico-in vivo approach stands as an interesting alternative to tackle and reduce drug product variability in biopharmaceutical quality. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Sensitivity of empirical metrics of rate of absorption in bioequivalence studies.

    Science.gov (United States)

    Ring, A; Tothfalusi, L; Endrenyi, L; Weiss, M

    2000-05-01

    The sensitivity and effectiveness of indirect metrics proposed for the assessment of comparative absorption rates in bioequivalence studies [Cmax, Tmax, partial AUC (AUCp), feathered slope (SLf), intercept metric (I)] were originally tested by assuming first-order absorption. The present study re-evaluates their sensitivity performances using the more realistic inverse Gaussian (IG) model characterizing the input process for oral drug administration. Simulations were performed for both the first-order or exponential model (EX) which is determined by only one parameter, the mean absorption time (MAT = 1/k(a)), and the IG model, which additionally contains a shape parameter, the relative dispersion of absorption time distribution (CV2A). Kinetic sensitivities (KS) of the indirect metrics were evaluated from bioequivalence trials (error free data) generated with various ratios of the true parameters (MAT and CV2A) of the two formulations. The behavior of the metrics was similar with respect to changes in MAT ratios with both models: KS was low with Cmax, moderate with SLf and AUCp, and high with I and Tmax following correction for apparent lag time (Tlag). Changes of the shape parameter CV2A, however, were not detectable by Cmax, Tmax, SLf, and AUCp. Changes in both MAT and CV2A were well reflected by I with CV2A - ratio > 1. I exhibited approximately full KS also with CV2A - ratio correction was first applied for the apparent lag time. The time profile of absorption rates is insufficiently characterized by only one parameter (MAT). Indirect metrics which are sensitive enough to detect changes in the scale and shape of the input profile could be useful for bioequivalence testing. Among the tested measures, I is particularly promising when a correction is applied for Tlag.

  9. Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

    KAUST Repository

    Al-Talla, Zeyad

    2011-01-01

    Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. Methods: A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC0-∞, AUC 0-t, Cmax, Ke, tmax and t 1/2 were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. Results: 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19-45 years); height, 175.8 (10.6) cm (range 159.0-192.0 cm); weight, 75.6 (11.0) kg (range 58-101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3-28 kg/m2)) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. Conclusion: The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra. ©2011 Dustri-Verlag Dr. K. Feistle.

  10. Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin.

    Science.gov (United States)

    Al-Talla, Z A; Akrawi, S H; Emwas, A-H M

    2011-07-01

    The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC(0-∞), AUC(0-t), C(max), K(e), tmax and t(1/2) were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19 - 45 years); height, 175.8 (10.6) cm (range 159.0 - 192.0 cm); weight, 75.6 (11.0) kg (range 58 - 101 kg); and body mass index, 24.4 (1.8) kg/m² (range 21.3 - 28 kg/m²) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra.

  11. Pharmacokinetic bioequivalence studies of a fixed-dose combination of tamsulosin and dutasteride in healthy volunteers.

    Science.gov (United States)

    Fossler, Michael J; Collins, David A; Thompson, Meg M; Nino, Antonio; Bianco, Joseph J; Chetty, Dushen

    2014-05-01

    The combination of dutasteride and tamsulosin may be more effective for the treatment of symptomatic benign prostatic hyperplasia than either treatment alone. We report the results of three pharmacokinetics and tolerability studies, which used a dutasteride/tamsulosin HCl (0.5 mg/0.2 mg) fixed-dose combination (FDC) capsules containing a small dutasteride soft gelatin capsule (smaller than commercial Avodart™) and modified-release tamsulosin pellets that have different amounts of enteric coating. These studies compared the test products to commercial Avodart™ (dutasteride 0.5 mg) and two different commercial tamsulosin HCl 0.2 mg products, Harnal™ Capsules or Harnal-D™ Tablets, which are reportedly bioequivalent to each other. All three studies were randomized single-dose studies in healthy male adults. Study 1 [N = 86 (NCT01254071)] was a two-period crossover study of a dutasteride/tamsulosin HCl FDC versus coadministered Avodart™ and Harnal-D™ Tablets. The pharmacokinetics of both dutasteride and tamsulosin were studied. Study 2 [N = 27 (NCT01471678)] was a four-period crossover study of dutasteride/tamsulosin HCl FDC formulations versus Avodart™ and Harnal™ Capsules or Harnal-D™ Tablets. Only the pharmacokinetics of tamsulosin were studied. Study 3 [N = 40 (NCT01495026)] was a two-period study of dutasteride/tamsulosin HCl FDC formulations versus coadministered Avodart™ and Harnal-D™ Tablets. In this study, only the pharmacokinetics of tamsulosin were studied. Study 2 assessed fed-state pharmacokinetics. Studies 1 and 3 assessed fed- and fasted-state pharmacokinetics. All dutasteride/tamsulosin HCl FDC formulations and coadministered treatments were well-tolerated. In Study 1, the FDC dutasteride was bioequivalent to Avodart™ coadministered with tamsulosin under fed and fasted conditions. In Study 1, the FDC tamsulosin had a slower release than commercial Harnal-D™ Tablets coadministered with dutasteride (fed and fasted

  12. Pharmacokinetic comparison and bioequivalence evaluation of losartan/ hydrochlorothiazide tablet between Asian Indian and Japanese volunteers.

    Science.gov (United States)

    Kumar, Sudershan; Monif, Tausif; Khuroo, Arshad; Reyar, Simrit; Jain, Rakesh; Singla, Ajay K; Kurachi, Kazuya

    2014-01-01

    To demonstrate the bioequivalence between the test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablet and evaluate the effect of ethnicity on pharmacokinetics properties of losartan, losartan carboxylic acid and hydrochlorothiazide on healthy Asian Indian and Japanese volunteers. Randomized, open-label, crossover, bioavailability studies were conducted separately in healthy Asian Indian and Japanese volunteers. One tablet either of test or of reference product was administered after 10 hours of overnight fasting. After dosing, serial blood samples were collected for a period of 48 hours for both the studies. Plasma samples were analyzed for losartan, losartan carboxylic acid and hydrochlorothiazide by a validated liquid chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic parameters AUC0-t, AUC0-∞, Cmax, tmax, and other pharmacokinetics parameters were determined from plasma concentration-time profiles for both test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablets. Statistical evaluations were done to evaluate bioequivalence between generic test formulation (EPR0001) and Japanese reference product (Preminent®). Losartan, losartan carboxylic acid and hydrochlorothiazide were well tolerated by subjects in all periods of each study under fasted conditions. No serious adverse events were observed. The ratios of least square means for AUC0-t and Cmax and the affiliated 90% confidence intervals were within acceptance range recommended by PMDA. Marginal differences were observed in pharmacokinetic values of Asian Indian and Japanese volunteers. The results of these bioavailability studies indicate that the test formulation of losartan/hydrochlorothiazide 50 + 12.5 mg (EPR0001) tablets is bioequivalent to marketed Preminent® reference formulation in Asian Indian and Japanese volunteers, when administered under fasting conditions. Both test and reference formulations were well tolerated

  13. 77 FR 75439 - Guidances for Industry and Investigators on Safety Reporting Requirements for Investigational New...

    Science.gov (United States)

    2012-12-20

    ...] Guidances for Industry and Investigators on Safety Reporting Requirements for Investigational New Drug Applications and Bioavailability/Bioequivalence Studies, and a Small Entity Compliance Guide; Availability... Reporting Requirements for INDs and BA/BE Studies'' and ``Safety Reporting Requirements for INDs and BA/BE...

  14. A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

    Science.gov (United States)

    Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

    2011-06-01

    The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

  15. Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation.

    Science.gov (United States)

    Kurczewski, Renee; Bowen, Chet; Collins, David; Zhu, John; Serbest, Gulyeter; Manyak, Michael

    2017-09-01

    A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart ® ) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration-vs-time data, a noncompartmental method was used to calculate the maximum observed serum concentration (C max ) and area under the serum concentration-time curve (AUC 0-t ) for dutasteride and tamsulosin, and AUC 0-∞ for tamsulosin. The 90% confidence intervals for the ratios of the C max and AUC 0-t (for dutasteride and tamsulosin) and for AUC 0-∞ (for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states. © 2017, The American College of Clinical Pharmacology.

  16. Percutaneous penetration of methyl nicotinate from ointments using the laser Doppler technique: bioequivalence and enhancer effects.

    Science.gov (United States)

    Remane, Yvonne; Leopold, Claudia S; Maibach, Howard I

    2006-12-01

    Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increased cutaneous microcirculation induced by methyl nicotinate (MN). Bioequivalence of a test and a standard preparation (vehicles: light mineral oil and medium chain triglycerides, respectively) was confirmed according to the pilot study of the FDA Guidance for Industry "Topical dermatologic corticosteroids: In Vivo bioequivalence" applying the staggered application and synchronized removal method for one defined concentration. Furthermore, the influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w diethylene glycol monoethyl ether) on MN penetration was investigated. It was shown that DMSO and diethylene glycol monoethyl ether altered cutaneous microcirculation and thus MN penetration in comparison to the standard formulation. However, true penetration enhancement could only be proved with diethylene glycol monoethyl ether resulting from an improved drug solubility in the skin which was confirmed by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.

  17. Evaluation of statistical power function for various diclofenac bioequivalence trials with different subject numbers.

    Science.gov (United States)

    Popović, Jovan; Mikov, Momir; Sabo, Ana; Jakovljević, Vida

    2009-01-01

    This study presents application of statistical power function for the t-test and ANOVA F-test on the evaluation of diclofenac bioequivalence in trials with the wide variations in sample sizes (N = 12, 18 and 24). The power function, together with appropriate equations tables and figures, is used to calculate the power of the ANOVA for crossover design, the number of subjects for a given value of power and the minimum detectable difference in treatment means for different pharmacokinetic parameters of the formulations. The power of the trial with a small, sample size (N = 12) to detect 20% differences between diclofenac formulations is shown to be more than 0.9 and almost the same as the power of the trial with a large sample size (N = 24). In all trials for all pharmacokinetic parameters the power to detect 20% difference is shown to be more than 0.8. For the power of 0.8, the needed subject number to detect 20% difference in treatment means is the same or smaller than used and the minimum detectable difference is smaller than 20% in all our trials. This investigation shows that bioequivalence studies with small number of subjects (N = 12) may be quite adequate for valid conclusions.

  18. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

    Directory of Open Access Journals (Sweden)

    Rita R Alloway

    2017-11-01

    Full Text Available Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand" product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant.From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35 or liver transplant (n = 36. Abbreviated New Drug Applications (ANDA data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug

  19. Pharmacogenetic relevance of the CYP2C9*3 allele in a tenoxicam bioequivalence study performed on Spaniards.

    Science.gov (United States)

    Peiró, A M; Novalbos, J; Zapater, P; Moreu, R; López-Rodríguez, R; Rodríguez, V; Abad-Santos, F; Horga, J F

    2009-01-01

    We performed a study to quantify CYP2C9 and CYP2C8 alleles influence on the variability observed in tenoxicam pharmacokinetic (PK) and implication in a bioequivalence study design performed on Spaniards. Eighteen healthy volunteers were included in an open, randomized, crossover, phase I bioequivalence study. Significant increases were found in CYP2C9*3 alleles vs. *1 and *2 in AUC(0-infinity) (median (min-max)): 256 (230-516) vs. 150 (100-268) and 169 (124-197) microg h/mL (p<0.01) and half-life time (t1/2) 102 (79-36) vs. 56 (45-94) and 64 (60-80)h (p<0.01). Non-significant differences were observed in C(max) 1.9 (1.8-2.9) vs. 2.4 (1.7-3.4), 2.5 (1.6-2.9) microg/mL or in according to CYP2C8 alleles presence. CYP2C9*3 allele is associated to a longer elimination time of tenoxicam. PK parameters calculated in bioequivalence studies (AUC(0-infinity), t1/2) may be influenced by the presence of CYP2C9*3 allele resulting in a high variability. Thus, bioequivalence studies of tenoxicam formulations should be designed considering genotype profile.

  20. Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Kemme, M J; Burggraaf, J

    2001-01-01

    The aim of the study was to investigate the cutaneous bioequivalence of a lipophilic model drug (lidocaine) applied in a novel topical microemulsion vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a pharmacokinetics microdialysis model and a pharmacodynamic method....

  1. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

    Directory of Open Access Journals (Sweden)

    Zhou X

    2015-02-01

    Full Text Available Xiao Zhou, Ji Liu Department of Anesthesia, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Abstract: This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4% for the area under the plasma concentration–time curve (AUC from time zero to the last measurable concentration, 99.6% (94.2%–102.7% for the AUC from administration to infinite time, and 100.8% (93.1%–106.4% for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules were bioequivalent. Keywords: tramadol hydrochloride, in vitro release, pharmacokinetic, bioequivalence, fluorescence detector

  2. Manual for best practice for emergency response procedures, part 4: a checklist of best practice requirements for the prevention and management of inrushes, fires, explosions and other emergencies.

    CSIR Research Space (South Africa)

    Spencer, KC

    2000-02-01

    Full Text Available PRACTICE FOR EMERGENCY RESPONSE PROCEDURES PART 4 A CHECKLIST OF BEST PRACTICE REQUIREMENTS FOR THE PREVENTION AND MANAGEMENT OF INRUSHES, FIRES, EXPLOSIONS AND OTHER EMERGENCIES Authors: K C Spencer, D M Walters, T P T Page and A G du Plessis... CHECKLIST FOR BEST PRACTICES PAGE 1 Part 1 Prevention of inrushes, fires, explosions and other emergencies Ref. ISSUE Y/N/? ACTION 1 Control mechanism for administration of CoPs, procedures & standards. 2 Introduction of hazards...

  3. A study on Requirements of Data Base Translator for APR1400 Computerized Procedure System at Shin-Hanul unit 1 and 2

    International Nuclear Information System (INIS)

    Seong, Nokyu; Lee, Sungjin

    2015-01-01

    The CPS is one of the Man Machine Interface (MMI) resources and the CPS can directly display plant graphic objects which are in the Digital Control System (DCS). And the CPS can send a request to DCS to provide DCS screen which is called step support display through DCS link button on a computerized procedure. The procedure writers can insert DCS graphic information to computerized procedure through data base which is provided by CPS Editing System (CPSES). The data base which is provided by CPSES conforms to the naming rule of DCS graphic objects. The naming rule of DCS graphic objects is defined by vendor thus status of DCS graphic objects which are in computerized procedure at Shin-Kori plant cannot be displayed on CPS at Shin-Hanul plant. To use computerized procedure which is written by other plant procedure writer, DCS graphic objects shall be translated by its plant data base. This paper introduces requirements of data base translator to reduce translation and re-inserting graphic objects burden. This paper introduces the requirements of data base translator of CPSES for APR1400 CPS at Shin-Hanul unit 1 and 2. The translator algorithms shall be tested to update data base of CPSES effectively. The prototype of translator is implemented and is being tested using real plant DB. This translator can be applied to Shin- Hanul unit1 and 2 through software V and V

  4. [Pharmacokinetics and bioequivalence of atorvastatin calcium tablets in healthy male Chinese volunteers].

    Science.gov (United States)

    Shen, Yi; Zhang, Yi-fan; Chen, Xiao-yan; Guo, Li-xia; Zhong, Da-fang

    2012-03-01

    To compare the bioequivalence and pharmacokinetics of national made and imported atorvastatin in healthy male Chinese volunteers after single oral administration. This randomized sequence, open-label, two-period crossover study with a one-week washout period between doses was performed in 24 fasting healthy Chinese males. They were randomly assigned to receive 20 mg of either the test (national made) or reference (imported) formulation orally. The blood samples were collected over a 72-hour period. Plasma concentrations of parent atorvastatin (AT), ortho-hydroxy-atorvastatin (o-OAT) and para-hydroxy-atorvastatin (p-OAT) were simultaneously determined using the validated liquid chromatography-tandem mass spectrometry method, the bioequivalence was also evaluated throughout the study. The main pharmacokinetic parameters of test and reference formulations were as follows: the values of C(max) for AT were (10.6 ± 11.9) µg/L and (10.6 ± 9.8) µg/L, t(1/2z) were (11.4 ± 3.9) h and (11.4 ± 5.3) h, AUC(0-t) were (54.2 ± 37.4) µg×h(-1)×L(-1) and (51.7 ± 34.1) µg×h(-1)×L(-1), respectively. The values of C(max) for o-OAT were (7.8 ± 4.5) µg/L and (7.6 ± 4.3) µg/L, t(1/2z) were (12.3 ± 4.2) h and (11.9 ± 3.4) h, AUC(0-t) were (96.8 ± 48.2) µg×h(-1)×L(-1) and (92.3 ± 44.4) µg×h(-1)×L(-1), respectively. The values of C(max) for p-OAT were (0.5 ± 0.4) µg/L and (0.4 ± 0.3) µg/L, t(1/2z) were (18.4 ± 12.4) h and (23.3 ± 17.8) h, AUC(0-t) were (15.9 ± 12.3) µg×h(-1)×L(-1) and (13.8 ± 8.11) µg×h(-1)×L(-1), respectively. The relative bioavailability of AT and o-OAT in test formulation were (105.3 ± 20.7)% and (107.8 ± 23.2)%, respectively. The 90% confidence interval of the test/reference geometric mean ratios of AUC(0-t) for AT and o-OAT were (97.7 - 110.5)% and (98.3 - 111.3)%, C(max) for AT and o-OAT were (75.8 - 114.0)% and (90.6 - 122.9)%, they were all located within the bioequivalence criteria range (80% - 125% for AUC, and 70% - 143

  5. Pharmacokinetics and bioequivalence study of aniracetam after single-dose administration in healthy Chinese male volunteers.

    Science.gov (United States)

    Tian, Yuan; Zhang, Jing-Jing; Feng, Shu-Dan; Zhang, Zun-Jian; Chen, Yun

    2008-01-01

    The pharmacokinetics of aniracetam (CAS 72432-10-1) in Chinese healthy male volunteers was investigated for the first time. Twenty male volunteers were enrolled into this open, randomized, single blind two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg (2 x 200 mg/capsule) aniracetam as a test or reference formulation with a 3-day washout period between the two preparations. The plasma concentrations of aniracetam were analyzed by a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters of the test and reference formulations were estimated as follows: The maximum plasma concentrations (Cmax) were 8.75 +/- 7.82 and 8.65 +/- 8.70 ng/mL, Tmax were 0.4 +/- 0.1 and 0.4 +/- 0.1 h, and plasma elimination half-lives (t(1/2)) were 0.47 +/- 0.16 and 0.49 +/- 0.24 h, respectively. The AUC(0-t) values demonstrated nearly identical bioavailability of aniracetam from the examined formulations. AUC(0-2.5) values were 4.53 +/- 6.62 and 4.76 +/- 6.65 ng h/mL, the areas under the plasma concentration-time curve (AUC(0-infinity) were 4.62 +/- 6.66 and 4.85 +/- 6.71 ng h/mL for the test and reference formulation, respectively. No statistical differences were observed for Cmax, and AUC(0-infinity) for aniracetam. The 90% confidence limits calculated for AUC and Cmax of aniracetam were within the standard bioequivalence range (80%-125% for AUC and Cmax). Therefore, the aniracetam test formulation can be regarded as bioequivalent to the aniracetam reference formulation.

  6. Bioequivalence and adhesion evaluation of transdermal clonidine following a change in excipient supplier.

    Science.gov (United States)

    Ehrlich, Jerome; Beck, Bonnie; Thiedmann, Ralf; Marzin, Kristell; MacGregor, Thomas

    2016-10-01

    To evaluate the bioequivalence (BE), safety, tolerability, and adhesion of Oppanol® polyisobutylene (PIB)-containing transdermal therapeutic system (TTS) formulation (test treatment, T) with VistanexTM PIB-containing TTS formulation (reference treatment, R) of clonidine. This randomized, double-blind, 2-way crossover study comprised a 7-day treatment with 0.3 mg clonidine/24 h (T1/R1), a 7-day washout, and another 7-day treatment (R1/T1) period. After a 3-day washout period, subjects used T2 and R2 (each 0.1 mg clonidine/24 h) simultaneously in the 7-day adhesion phase. Primary endpoints were AUC0-168 and Cavg. Secondary endpoints were AUC0-∞ and Cmax. Additional endpoints included adhesion properties for all phases. For the primary endpoint, the geometric mean (gMean) ratios for test/reference treatment were calculated with BE defined as 90% confidence interval (CI) between 80 and 125%. 58 subjects (mean age, 41.3 years) received treatment (T1/R1, n = 29; R1/T1, n = 29); 55 completed the adhesion phase. BE criteria were met for the primary and secondary endpoints. Adjusted gMean ratios for T1/R1 were 102.3% (90% CI: 95.7%, 109.4%) for AUC0-168; 104.3% (90% CI: 98.4%, 110.5%) for Cavg; 102.8% (90% CI: 97.3%, 108.6%) for AUC0-∞; and 104.0% (90% CI: 98.2%, 110.3%) for Cmax. Mean adhesion was greater than 90% for all four patch types when data from all assessment times were included. Most frequently reported adverse events were general disorders and local irritation. Clonidine Oppanol® PIB-containing TTS formulation was bioequivalent to VistanexTM PIB-containing TTS formulation and had similar adhesive properties. Both doses and formulations of clonidine-TTS were well tolerated.

  7. Bioequivalence evaluation of two brands of aceclofenac 100 mg tablets (Aceclofar and Bristaflam) in healthy human volunteers.

    Science.gov (United States)

    Najib, Naji; Idkaidek, Nasir; Beshtawi, M; Bader, Mohammed; Admour, Isra'; Alam, S Mahmood; Zaman, Q; Dham, Ruwayda

    2004-04-01

    A randomized, two-way, crossover, bioequivalence study in 24 fasting, healthy, male volunteers was conducted to compare two brands of aceclofenac 100 mg tablets, Aceclofar (Julphar, UAE) as test and Bristaflam (Bristol Myers Squibb, Egypt) as the reference product. The drug was administered with 240 ml of water after a 10 h overnight fast on two treatment days separated by 1 week washout period. After dosing, serial blood samples were collected for a period of 24 h. Plasma harvested from blood was analysed for aceclofenac by a validated HPLC method with UV-visible detection capable of detecting aceclofenac in the range 0.2-8.0 microg/ml with the limit of quantitation as 0.2 microg/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0- infinity ), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations for both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0- infinity), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval (100.0%-106.4% for AUC(0-t), 100.2%-106.8% for AUC(0- infinity ); 83.3%-102.8% for C(max)) of test/reference ratio for these parameters were found to be within the bioequivalence acceptance range of 80%-125%. Based on these statistical inferences, it was concluded that Aceclofar is bioequivalent to Bristaflam. Copyright 2004 John Wiley & Sons, Ltd.

  8. Bioequivalence evaluation of two brands of fluoxetine 20 mg capsules (Flutin and Prozac) in healthy human volunteers.

    Science.gov (United States)

    Najib, Naji M; Idkaidek, Nasir; Beshtawi, Muntaser; Mohammed, B; Admour, Isra; Alam, S Mahmood; Dham, Ruwayda; Qumaruzaman

    2005-09-01

    A bioequivalence study of two oral formulations of 20 mg fluoxetine was carried out in 24 healthy volunteers following a single dose, two-sequence, crossover randomized design at International Pharmaceutical Research Centre (IPRC), Amman, Jordan. The two formulations were Flutin capsules (Julphar, UAE) as test and Prozac capsules (Eli Lilly, UK) as reference product. Test and reference capsules were administered to each subject after an overnight fasting on two treatment days separated by a 28 day washout period. After dosing, serial blood samples were collected for a period of 360 h. Plasma harvested from blood was analysed for fluoxetine by a sensitive, reproducible and accurate LC-MS method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations for both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval (94.60%-106.41% for AUC(0-t), 94.6%-108.14% for AUC(0-infinity); 91.88%-103.65% for C(max)) for test/reference ratio of these parameters were found within FDA acceptance range of 80%-125%. Based on these statistical inferences, it was concluded that Flutin is bioequivalent to Prozac and can be used interchangeably in medical practice. Copyright 2005 John Wiley & Sons, Ltd

  9. A pharmacokinetic and bioequivalence study of Contiflo ICON 400 µg tablets in healthy Indian subjects.

    Science.gov (United States)

    Monif, T; Arora, V; Madan, S; Arora, R; Balaji, A; Jha, D; Thudi, N R

    2010-12-01

    Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in human prostate. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of benign prostatic hypertrophy. A new formulation Contiflo ICON 400 µg has been developed by Ranbaxy Laboratories Limited, India similar to Flomaxtra XL 400 µg of Astellas Pharma Limited, United Kingdom. This product is specifically designed to achieve a more consistent plasma concentration over a period of 24-h, a lower maximum plasma concentration (Cmax) and an independence of pharmacokinetics (PKs) on food intake. The objective of the present study was to evaluate the pharmacokinetics and bioequivalence of the new formulation Contiflo ICON 400 µg of Ranbaxy Laboratories Limited, India and Flomaxtra XL 400 µg prolonged release tablets (containing tamsulosin hydrochloride prolonged release 400 µg) of Astellas Pharma Limited, United Kingdom. Study was conducted as an open label, balanced, randomized, two-treatment, two-period, two-sequence, cross over, single-dose bioequivalence study in 32 adult male human subjects under fed conditions. The mean (range) age, weight and height of the study subjects were 27.03 years (19 - 40 years), 57.19 kg (48 - 72 kg) and 166.81 cm (154 - 181 cm) respectively. Blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 20, 24, 36, 48, 72, and 96 h post dose in each period. Plasma samples were analyzed for tamsulosin by using validated liquid chromatographic mass spectrometry (LC-MS/MS) method. The Mean ± SD of pharmacokinetic parameters tmax, Cmax, AUC24, AUClast and AUCinf for Tamsulosin were 11.741 ± 4.7201 and 12.155 ± 6.3077 h, 10.7614 ± 4.76709 and 10.4954 ± 5.08979 ng/ml, 171.4674 ± 77.39695 and 160.6738 ± 77.98628 ng.h/ml, 262.7771 ± 150.21432 and 250.6854 ± 156.75581 ng

  10. RELAP-7 Software Verification and Validation Plan - Requirements Traceability Matrix (RTM) Part 2: Code Assessment Strategy, Procedure, and RTM Update

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jun Soo [Idaho National Lab. (INL), Idaho Falls, ID (United States); Choi, Yong Joon [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis Lee [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-09-01

    This document addresses two subjects involved with the RELAP-7 Software Verification and Validation Plan (SVVP): (i) the principles and plan to assure the independence of RELAP-7 assessment through the code development process, and (ii) the work performed to establish the RELAP-7 assessment plan, i.e., the assessment strategy, literature review, and identification of RELAP-7 requirements. Then, the Requirements Traceability Matrices (RTMs) proposed in previous document (INL-EXT-15-36684) are updated. These RTMs provide an efficient way to evaluate the RELAP-7 development status as well as the maturity of RELAP-7 assessment through the development process.

  11. Bioequivalence study of a generic Risperidone (Iperdal® in healthy Thai male volunteers

    Directory of Open Access Journals (Sweden)

    Werawath Mahatthanatrakul

    2008-05-01

    Full Text Available The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal® with a reference formulation (Risperdal® when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC-UV method modified from Avenosoet al. (2000. Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by “Two Way Analysis of Variance” (ANOVA. Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78 and 32.58±19.77 (range 5.29-84.56 ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48 of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32 and 144.03±127.37 (range 16.27-456.0 ng.hr/ml, respectively. The time to maximum concentration (Tmax of theinnovator and the generic product were 0.97±0.41(range 0.5-2 and 1.02±0.32 (range 0.5-1.5 hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.

  12. 45 CFR 264.30 - What procedures exist to ensure cooperation with the child support enforcement requirements?

    Science.gov (United States)

    2010-10-01

    ... the child support enforcement requirements? 264.30 Section 264.30 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES OTHER ACCOUNTABILITY PROVISIONS What Specific Rules Apply...

  13. Comparison of the Number of Image Acquisitions and Procedural Time Required for Transarterial Chemoembolization of Hepatocellular Carcinoma with and without Tumor-Feeder Detection Software.

    Science.gov (United States)

    Iwazawa, Jin; Ohue, Shoichi; Hashimoto, Naoko; Mitani, Takashi

    2013-01-01

    Purpose. To compare the number of image acquisitions and procedural time required for transarterial chemoembolization (TACE) with and without tumor-feeder detection software in cases of hepatocellular carcinoma (HCC). Materials and Methods. We retrospectively reviewed 50 cases involving software-assisted TACE (September 2011-February 2013) and 84 cases involving TACE without software assistance (January 2010-August 2011). We compared the number of image acquisitions, the overall procedural time, and the therapeutic efficacy in both groups. Results. Angiography acquisition per session reduced from 6.6 times to 4.6 times with software assistance (P acquisition significantly decreased from 10.4 times to 8.7 times with software usage (P = 0.004). The mean procedural time required for a single session with software-assisted TACE (103 min) was significantly lower than that for a session without software (116 min, P = 0.021). For TACE with and without software usage, the complete (68% versus 63%, resp.) and objective (78% versus 80%, resp.) response rates did not differ significantly. Conclusion. In comparison with software-unassisted TACE, automated feeder-vessel detection software-assisted TACE for HCC involved fewer image acquisitions and could be completed faster while maintaining a comparable treatment response.

  14. Meta-analysis for bioequivalence studies: interchangeability of generic drugs and similar containing Hydrochlorothiazide is possible but not with Enalapril Maleate.

    Science.gov (United States)

    Lopes, Renato Almeida; Neves, Francisco de Assis Rocha

    2010-01-01

    The generic drugs program provided a better population's access to medicines. To ensure interchangeability between a brand-name and generic or similar drugs is necessary that they are bioequivalent. With the growing number of generic drugs, it is common for patients to replace a generic to another or one similar. However, this exchange can not guarantee the maintenance of bioequivalence. To evaluate the safety interchangeability between different generic and similar drugs with Hydrochlorothiazide and Enalapril Maleate, a meta-analysis was carried out with several bioequivalence studies with these drugs. Data from bioequivalence of generic and similar drugs approved by the National Health Surveillance Agency (Anvisa) (drug regulatory agency in Brazil) were used. The compatibility of data from each study was analyzed and the determination of a confidence interval for the differences between the means of pharmacokinetic parameters, area under the curve (ASC0-t) and maximum plasma concentration (Cmax), was made for each study by meta-analysis. The interchangeability between the combinations of the three products with Hydrochlorothiazide was confirmed based on the obtained confidence intervals. For the drugs studied with Enalapril Maleate interchangeability has not been confirmed for 50% of the product comparisons. The exchange was established between the three products with hydrochlorothiazide. However, for the Enalapril Maleate half of the products studied are not interchangeable, considering they do not match the established intervals for bioequivalence tests, so the pharmacokinetics behavior and thus the effectiveness of the product may be changed.

  15. Evaluation of some properties of individual bioequivalence (IBE) from replicate-design studies.

    Science.gov (United States)

    Tothfalusi, L; Endrenyi, L

    2001-04-01

    One of the claimed benefits of the individual bioequivalence (IBE) approach has been that the aggregate regulatory model rewards a test formulation when it has a within-subject variation smaller than the reference product. Hauck et al. [1996] demonstrated that, in the absence of random variations, this property of IBE was due to the tradeoff between the difference of the means and the deviation between the intrasubject variances of the two formulations. The tradeoff was a consequence of the aggregate regulatory model. However, calculations of Endrenyi and Hao [1998] showed that, in the presence of random variations, not only rewards but also penalties can arise due to chance alone. A data set of 55 investigations made public by the FDA in 1999 and containing replicate crossover designs was analyzed. Two parameters, AUC and Cmax, were determined in each investigation. The analyses of the FDA data indicate that: rewards and penalties occur at similar frequencies, large rewards and penalties are recorded quite often, and the aggregate IBE model is rather insensitive to the difference between the estimated means and is compatible with the frequent occurrence of large deviations. Rewards and penalties, apparently arising from random variations, can affect regulatory decisions on the acceptance of IBE and can lead to incorrect conclusions.

  16. Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats.

    Science.gov (United States)

    Baracho, Nilo César do Vale; Arruda, Guilherme D'Andréa Saba; Alves, Lidinei José; Carneiro, Márcio Felipe Salomon; Siqueira, Matheus Teodoro Grilo; Arango, Héctor Gustavo; Marcos dos Reis, José

    2008-01-01

    High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR). Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. The use of generic drug and similars (A and B) drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.

  17. An evaluation of the procedures required to ensure consistent material supply in the Eastern Cape automotive industry

    Directory of Open Access Journals (Sweden)

    GS Horn

    2014-07-01

    Full Text Available There is a common perception that logistics practice and supply chain management have not yet reached the required international standards among all the supply chain members in the South African automotive industry. This article is based on a research study that investigated possible reasons for the inconsistent supply of materials in the Eastern Cape automotive industry specifically. Problems identified include the fact that suppliers are not evaluated on a regular basis and do not receive sufficient logistics training, while a commitment and will to development local suppliers is lacking. Recommendations made to the South African automotive industry include the improvement of development programmes to assist local suppliers in becoming world-class suppliers, better logistics training, more regular supplier assessments, as well as improved mutual communication among suppliers and motor vehicle assemblers.

  18. Pharmacokinetics and bioequivalence evaluation of two different atorvastatin calcium 10-mg tablets: A single-dose, randomized-sequence, open-label, two-period crossover study in healthy fasted Chinese adult males.

    Science.gov (United States)

    Liu, Yan-Mei; Pu, Hua-Hua; Liu, Gang-Yi; Jia, Jing-Ying; Weng, Li-Ping; Xu, Rong-Jing; Li, Guo-Xiu; Wang, Wei; Zhang, Meng-Qi; Lu, Chuan; Yu, Chen

    2010-07-01

    Atorvastatin calcium is a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor indicated for the prevention of cardiovascular disease and for the treatment of dyslipidemia. Information on the pharmacokinetics of atorvastatin in a Chinese population is lacking, and regulatory requirements necessitate a bioequivalence study for the marketing of a generic product in China. The aim of the present study was to assess the pharmacokinetics and bioequivalence of a test and branded reference formulation of atorvastatin calcium 10-mg tablets in healthy fasted Chinese male volunteers. This was a single-dose, randomized-sequence, open-label, 2-period crossover study with a 2-week washout period between doses. Healthy Chinese males were randomly assigned to receive 20 mg of either the test or reference formulation, and 13 blood samples were obtained over a 48-hour interval. Plasma concentrations of parent atorvastatin and ortho-hydroxy-atorvastatin (primary active metabolite) were simultaneously determined using a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters, including C(max), T(max), t((1/2)), AUC(0-t), and AUC(0-infinity)), were calculated. The 2 formulations were to be considered bioequivalent if 90% CIs for the log transformed ratios of AUC and C(max) of atorvastatin were within the predetermined bioequivalence range (0.80-1.25 for AUC and 0.70-1.43 for C(max)) as established by the State Food and Drug Administration of China. Tolerability was evaluated throughout the study by vital signs monitoring, physical examinations, 12-lead ECGs, and subject interviews on adverse events (AEs). A total of 66 subjects were assessed for inclusion; 20 were excluded prior to study initiation. Of the 46 healthy subjects (mean [SD] age, 24.1 [2.5] years; height, 170.8 [5.1] cm; weight, 64.6 [6.4] kg; body mass index (BMI), 22.1 [1.7] kg/m(2)) who completed the study, 45 subjects (mean [SD] age, 24.1 [2.5] years; height, 171.1 [4

  19. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

    Science.gov (United States)

    Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

    2017-02-01

    The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
.

  20. Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults.

    Directory of Open Access Journals (Sweden)

    Jayne Byakika-Tusiime

    Full Text Available Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune or the corresponding brand formulations (Epivir, Zerit, and Viramune.An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg, stavudine (40 mg, and nevirapine (200 mg in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC(0-12h and C(max. Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8-1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine C(max, 1.3 (0.99-1.71 and AUC(0-12h, 1.1 (0.87-1.38; lamivudine C(max, 0.8 (0.63-0.98 and AUC(0-12h, 0.8 (0.65-0.99; and nevirapine C(max, 1.1 (0.95-1.23 and AUC(0-12h, 1.1 (0.95-1.31. The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters.These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical.

  1. Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and equivalent doses of repaglinide and metformin tablets
.

    Science.gov (United States)

    Cho, Hea-Young; Ngo, Lien; Kim, Sang-Ki; Choi, Yoonho; Lee, Yong-Bok

    2018-04-12

    This study was conducted to determine whether a fixed-dose combination (FDC) tablet of repaglinide/metformin (2/500 mg) is equivalent to coadministration of equivalent doses of individual (EDI) tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. This study was conducted as an open-label, randomized, single-dose, two-period, two-sequence crossover design in 50 healthy Korean male subjects who received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and metformin were determined for up to 24 hours using a validated UPLC-MS/MS method. Bioequivalence was assessed according to current guidelines issued by the U.S. Food and Drug Administration (FDA) and Korean legislation. Tolerability was also evaluated throughout the study via subject interview, vital signs, and blood sampling. Point estimates (90% CIs) for AUC0-t, AUC0-∞, and Cmax based on EDI tablets were 110.07 (102.25 - 118.49), 109.90 (101.70 - 118.39), and 112.60 (101.49 - 124.85), respectively, for repaglinide. They were 95.18 (89.62 - 101.05), 95.00 (89.74 - 100.65), and 98.44 (92.72 - 104.50), respectively, for metformin. These results satisfied the bioequivalence criteria of 80.00 - 125.00% proposed by the FDA and Korean legislation. Results of pharmacokinetic analysis suggested that repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. Both formulations appeared to be well tolerated.
.

  2. Psychological Profile of Children Who Require Repetitive Surgical Procedures for Early Onset Scoliosis: Is a Poorer Quality of Life the Cost of a Straighter Spine?

    Science.gov (United States)

    Aslan, Cihan; Olgun, Z Deniz; Ertas, Erkan Sabri; Ozusta, Seniz; Demirkiran, Gokhan; Unal, Fatih; Yazici, Muharrem

    2017-09-01

    Cross-sectional study. Assess the psychosocial status of children with early-onset scoliosis (EOS) undergoing multiple procedures and evaluate associations with other variables. EOS may require repetitive surgical procedures to control deformity and preserve growth. These procedures impact patients' psychosocial status because of the repetitive surgeries. EOS patients 6-18 years, undergoing traditional growing rod treatment with more than 5 surgical procedures, and neurologically/mentally intact were included. Patients were screened for psychiatric disorders before inclusion. The Quality of Life Scale for Children (PedsQL), Strengths and Difficulties Questionnaire (SDQ) self-report form, Beck Depression Inventory, Children Depression Inventory (CDI), Beck Anxiety Inventory (BAI), and the Self-Report for Childhood Anxiety Related Disorders (SCARED) were completed by the children. PedsQL Parental Form and SDQ Parent Form were completed by their parents. Twenty-one patients (9 male, 12 female) met the inclusion criteria. Average age was 6.4 years (4-10.5) at index surgery, and 13.5 years (8-17) at final follow-up. The mean number of procedures was 13 (6-18). Mean follow-up was 83.9 months (36-122). Depression was observed in 23.8% of patients, and generalized anxiety disorder in 42.8%. Patients in the study group were more likely than the general population to have a psychiatric diagnosis. Number of procedures undergone was found to correlate negatively with BAI, SCARED, and the behavioral difficulties domain of SDQ parent form score and positively with emotional functioning, psychosocial health summary score, PedsQL total score, and increased social and physical functioning. Nonidiopathic etiology was found to be related to increased behavioral difficulties and lower functioning. A higher prevalence of depressive and anxiety symptoms was observed in patients with EOS along with dysfunctional areas of daily life. Other comorbidities may also contribute to dysfunction

  3. Bioequivalencia entre dos formulaciones comerciales de gliclazida en Colombia Bioequivalence between two commercial formulations of gliclazide in Colombia

    Directory of Open Access Journals (Sweden)

    Gloria Holguín Martínez

    2001-01-01

    Full Text Available Los formulaciones comerciales de Gliclazida de 80 mg – tabletas, los productos Glidiab® de Tecnoquímicas y Diamicron® de Euroetika-Elsevier, fueron sometidos a estudio para evaluar la equivalencia farmacéutica y la equivalencia biológica. Después de comprobar la equivalencia farmacéutica se llevó a cabo el estudio de la equivalencia biológica en 14 voluntarios sanos; la cuantificación de Gliclazida en plasma se realizó por la técnica de cromatografía líquida de alta resolución (HPLC. Los parámetros farmacocinéticos evaluados fueron: área bajo la curva (AUC de 0-60 horas, concentración máxima (Cmáx y el tiempo máximo (tmáx los cuales se analizaron estadísticamente con intervalos de confianza del 90.0% y un rango de aceptación para bioequivalencia del 80.0% al 125.0% para AUC y Cmáx y del 80.0% al 120.0% para el tmáx. Ambas formulaciones presentaron alta variabilidad inter e intrasujeto y se encontró que son bioequivalentes con respecto a AUC, pero no lo son con respecto a Cmáx y tmáx. Two commercial formulations of Gliclazide 80 mg tablets were studied in order to evaluate both pharmaceutical and biological equivalence, Glidiab® Tecnoquímicas Laboratories and Diamicron® Euroetika-Elsevier Laboratories. After proving the pharmaceutical equivalence, a bioequivalence was tested in 14 healthy volunteers and the determination of gliclazide in plasma was carried out by high-performance liquid chromatography (HPLC. The evaluated pharmacokinetic parameters were: area under the curve (AUC from 0 to 60 hours, maximum concentration (Cmax and time to maximum concentration (Tmax. In statistical analysis the 90.0% confidence intervals for AUC, Cmax and Tmax, and acceptance range for bioequivalence of 80.0%-125.0% to AUC and Cmax and acceptance range of 80:0%-120.0% to Tmax, were applied. Both formulations presented inter and intra subject high variability and it was found that they are bioequivalent in relation to AUC but

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

    Science.gov (United States)

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

    2017-01-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled “Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation.”1 The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole‐body framework.2 PMID:28571121

  5. Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence.

    Science.gov (United States)

    García-Arieta, Alfredo

    2014-12-18

    The aim of the present paper is to illustrate the impact that excipients may have on the bioavailability of drugs and to review existing US-FDA, WHO and EMA regulatory guidelines on this topic. The first examples illustrate that small amounts of sorbitol (7, 50 or 60mg) affect the bioavailability of risperidone, a class I drug, oral solution, in contrast to what is stated in the US-FDA guidance. Another example suggests, in contrast to what is stated in the US-FDA BCS biowaivers guideline, that a small amount of sodium lauryl sulphate (SLS) (3.64mg) affects the bioavailability of risperidone tablets, although the reference product also includes SLS in an amount within the normal range for that type of dosage form. These factors are considered sufficient to ensure that excipients do not affect bioavailability according to the WHO guideline. The alternative criterion, defined in the WHO guideline and used in the FIP BCS biowaivers monographs, that asserts that excipients present in generic products of the ICH countries do not affect bioavailability if used in normal amounts, is shown to be incorrect with an example of alendronate (a class III drug) tablets, where 4mg of SLS increases bioavailability more than 5-fold, although a generic product in the USA contains SLS. Finally, another example illustrates that a 2mg difference in SLS may affect bioavailability of a generic product of a class II drug, even if SLS is contained in the comparator product, and in all cases its amount was within the normal range. Therefore, waivers of in vivo bioequivalence studies (e.g., BCS biowaivers, waivers of certain dosage forms in solution at the time of administration and variations in the excipient composition) should be assessed more cautiously. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy.

    Science.gov (United States)

    Zarifpour, Mona; Andersson, Karl-Erik; Kelkar, Sneha S; Mohs, Aaron; Mendelsohn, Cathy; Schneider, Kerry; Marini, Frank; Christ, George J

    2017-01-01

    Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC) in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T 2 -weighted magnetic resonance imaging (MRI). Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC) following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks) post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume), consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers) of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

  7. Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

    Science.gov (United States)

    Estepp, Jeremie H; Melloni, Chiara; Thornburg, Courtney D; Wiczling, Paweł; Rogers, Zora; Rothman, Jennifer A; Green, Nancy S; Liem, Robert; Brandow, Amanda M; Crary, Shelley E; Howard, Thomas H; Morris, Maurine H; Lewandowski, Andrew; Garg, Uttam; Jusko, William J; Neville, Kathleen A

    2016-03-01

    Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA. © 2015, The American College of Clinical Pharmacology.

  8. Inclusion of service robots in the daily lives of frail older users: A step-by-step definition procedure on users' requirements.

    Science.gov (United States)

    García-Soler, Álvaro; Facal, David; Díaz-Orueta, Unai; Pigini, Lucia; Blasi, Lorenzo; Qiu, Renxi

    2018-01-01

    The implications for the inclusion of robots in the daily lives of frail older adults, especially in relation to these population needs, have not been extensively studied. The "Multi-Role Shadow Robotic System for Independent Living" (SRS) project has developed a remotely-controlled, semi-autonomous robotic system to be used in domestic environments. The objective of this paper is to document the iterative procedure used to identify, select and prioritize user requirements. Seventy-four requirements were identified by means of focus groups, individual interviews and scenario-based interviews. The list of user requirements, ordered according to impact, number and transnational criteria, revealed a high number of requirements related to basic and instrumental activities of daily living, cognitive and social support and monitorization, and also involving privacy, safety and adaptation issues. Analysing and understanding older users' perceptions and needs when interacting with technological devices adds value to assistive technology and ensures that the systems address currently unmet needs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

    Science.gov (United States)

    Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

    2013-03-01

    Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

  10. In vitro Approaches to Support Bioequivalence and Substitutability of Generic Proton Pump Inhibitors via Nasogastric Tube Administration.

    Science.gov (United States)

    Ren, Ping; Cui, Minglei; Anand, Om; Xia, Li; Zhao, Zhuojun J; Sun, Dajun; Sharp, Trueman; Conner, Dale P; Peters, John; Jiang, Wenlei; Stier, Ethan; Jiang, Xiaojian

    2017-11-01

    Administration of proton pump inhibitors (PPIs) through nasogastric tubes may present risks. If the PPI drug products are not prepared properly, clogging or obstruction of nasogastric tubes can pose a safety concern. In addition, the integrity of the enteric coating of the drug product may be damaged resulting in reduced bioavailability of the active moiety. From the perspective of administration of generic PPIs when compared to the reference drug product, differences in formulation can potentially result in a greater relative risk for the generic drug product. As part of the assessment of bioequivalence, the Office of Generic Drugs (OGD) has developed a suite of in vitro testing to compare the delivery of the generic and reference products via nasogastric tubes. These in vitro tests assess essential attributes associated with the likelihood of clogging and maintenance of the enteric coating. These in vitro tests include studies evaluating sedimentation, granule size distribution, drug recovery, and acid resistance. One of the challenges is that while the administration of PPIs through nasogastric tubes is common in clinical practice, this issue is not uniformly addressed in the FDA approved label of the reference drug products. This paper discusses the design and rationale for in vitro testing of PPI formulations with respect to bioequivalence via nasogastric tube administration and in addition, it summarizes commonly occurring deficiencies in the in vitro nasogastric tube testing of 14 recent Abbreviated New Drug Applications (ANDA) submitted for five generic PPI drug products.

  11. Concepts and procedures required for successful reduction of tensor magnetic gradiometer data obtained from an unexploded ordnance detection demonstration at Yuma Proving Grounds, Arizona

    Science.gov (United States)

    Bracken, Robert E.; Brown, Philip J.

    2006-01-01

    On March 12, 2003, data were gathered at Yuma Proving Grounds, in Arizona, using a Tensor Magnetic Gradiometer System (TMGS). This report shows how these data were processed and explains concepts required for successful TMGS data reduction. Important concepts discussed include extreme attitudinal sensitivity of vector measurements, low attitudinal sensitivity of gradient measurements, leakage of the common-mode field into gradient measurements, consequences of thermal drift, and effects of field curvature. Spatial-data collection procedures and a spin-calibration method are addressed. Discussions of data-reduction procedures include tracking of axial data by mathematically matching transfer functions among the axes, derivation and application of calibration coefficients, calculation of sensor-pair gradients, thermal-drift corrections, and gradient collocation. For presentation, the magnetic tensor at each data station is converted to a scalar quantity, the I2 tensor invariant, which is easily found by calculating the determinant of the tensor. At important processing junctures, the determinants for all stations in the mapped area are shown in shaded relief map-view. Final processed results are compared to a mathematical model to show the validity of the assumptions made during processing and the reasonableness of the ultimate answer obtained.

  12. Extended acclimatization is required to eliminate stress effects of periodic blood-sampling procedures on vasoactive hormones and blood volume in beagle dogs.

    Science.gov (United States)

    Slaughter, M R; Birmingham, J M; Patel, B; Whelan, G A; Krebs-Brown, A J; Hockings, P D; Osborne, J A

    2002-10-01

    Important in all experimental animal studies is the need to control stress stimuli associated with environmental change and experimental procedures. As the stress response involves alterations in levels of vasoactive hormones, ensuing changes in cardiovascular parameters may confound experimental outcomes. Accordingly, we evaluated the duration required for dogs (n = 4) to acclimatized to frequent blood sampling that involved different procedures. On each sampling occasion during a 6-week period, dogs were removed from their pen to a laboratory area and blood was collected either by venepuncture (days 2, 15, 34, 41) for plasma renin activity (PRA), epinephrine (EPI), norepinephrine, aldosterone, insulin, and atrial natriuretic peptide, or by cannulation (dogs restrained in slings; days 1, 8, 14, 22, 30, 33, 37, 40) for determination of haematocrit (HCT) alone (days 1 to 22) or HCT with plasma volume (PV; days 30 to 40). PRA was higher on days 2 and 15 compared with days 34 and 41 and had decreased by up to 48% by the end of the study (day 41 vs day 15; mean/SEM: 1.18/0.27 vs 2.88/0.79 ng ANG I/ml/h, respectively). EPI showed a time-related decrease from days 2 to 34, during which mean values had decreased by 51% (mean/SEM: 279/29 vs 134/20.9 pg/ml for days 2 and 34, respectively), but appeared stable from then on. None of the other hormones showed any significant variability throughout the course of the study. HCT was relatively variable between days 1 to 22 but stabilized from day 30, after which all mean values were approximately 6% lower than those between days 1 and 8. We conclude that an acclimatization period of at least 4 weeks is required to eliminate stress-related effects in dogs associated with periodic blood sampling.

  13. Bioequivalence assessment of Lovrak (Julphar, UAE) compared with Zovirax (Glaxo Wellcome, UK)--Two brands of Acyclovir--in healthy human volunteers.

    Science.gov (United States)

    Najib, Naji M; Idkaidek, Nasir; Beshtawi, Muntaser; Mohammed, B; Admour, Isra'; Alam, S Mahmood; Dham, Ruwayda

    2005-01-01

    Two studies were performed to assess the relative bioavailability of Lovrak (Julphar, UAE) compared with Zovirax (Glaxo Wellcome, UK) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved acyclovir tablets and the other acyclovir suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of acyclovir were administered as a single dose on 2 treatment days separated by 1 week washout period. After dosing, serial blood samples were collected for a period of 16 h. Plasma harvested from blood, was analysed for acyclovir by an HPLC method with UV detection. Various pharmacokinetic parameters including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2 and Kelm were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC0-t, AUC(0-proportional to), and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratio of these parameters were found within the bioequivalence acceptance range 80%-125%. Based on these statistical inferences it was concluded that a Lovrak tablet is bioequivalent to a Zovirax tablet and that Lovrak suspension is bioequivalent to Zovirax suspension. 2004 John Wiley & Sons, Ltd.

  14. A randomized, single-blind, Phase I trial (INVICTAN-1) assessing the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy subjects.

    Science.gov (United States)

    Hettema, Willem; Wynne, Christopher; Lang, Benjamin; Altendorfer, Mario; Czeloth, Niklas; Lohmann, Ragna; Athalye, Sandeep; Schliephake, Dorothee

    2017-08-01

    This Phase I trial (INVICTAN®-1) evaluated three-way bioequivalence and safety of BI 695502 a bevacizumab biosimilar candidate, and reference product bevacizumab from two sources (US-approved Avastin®, Genentech; EU-approved Avastin, Roche). Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early. The primary end point was area under the concentration-time curve (AUC) of the analyte in plasma from time zero extrapolated to infinity (AUC 0-∞ ). Other pharmacokinetic (PK) parameters, safety, and in vitro binding affinity were also evaluated. The interim analysis demonstrated three-way bioequivalence for all comparisons. The confidence intervals around the geometric mean ratios of the primary and secondary PK parameters were within the predefined acceptance ranges. Study drugs were well tolerated with no clinically relevant differences in safety. BI 695502 and US- and EU-approved Avastin showed three-way bioequivalence with similar safety profile. NCT01608087.

  15. A comparative analysis of biopharmaceutics classification system and biopharmaceutics drug disposition classification system: a cross-sectional survey with 500 bioequivalence studies.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Chiann, Chang; Dressman, Jennifer B; Storpirtis, Silvia

    2013-09-01

    Although policies of waiving bioequivalence studies are part of the legal framework of various regulatory agencies, there is no harmonization with regard to extension of the biowaiver to drugs other than those with high solubility and high permeability, nor is there any consensus or official endorsement of the biopharmaceutics drug disposition classification system (BDDCS). To better understand the applicability of the biowaiver, we carried out a cross-sectional survey to estimate the relative risk of obtaining nonbioequivalent (non-BE) or bioinequivalent (BIE) results for drug products containing drugs belonging to each of the biopharmaceutics classification system (BCS) and BDDCS classes. Five hundred bioequivalence studies were randomly sampled from a database of the Brazilian Health Surveillance Agency (ANVISA). The drugs were classified according to the BCS and BDDCS, to evaluate how characteristics related to drug and dosage form influence the outcome of bioequivalence studies. The relative risk of obtaining a non-BE result was approximately four times lower for drugs in classes 1 and 3 of BCS or BDDCS when compared with class 2 drugs. Thus, it seems that the final outcome of a bioequivalence study is strongly influenced by the solubility of the drug, but not by its intestinal permeability or extent of metabolism. Copyright © 2013 Wiley Periodicals, Inc.

  16. Quantitative analysis of valsartan by two-dimensional liquid chromatography (2D-HPLC) and its application in a bioequivalence study in Chinese volunteers
.

    Science.gov (United States)

    Zhang, Min; Deng, Yang; Cai, Hua-Lin; Fang, Ping-Fei; Yan, Miao; Zhang, Bi-Kui; Wu, Yan-Qin

    2017-04-01

    To develop a sensitive, two-dimensional liquid chromatography (2D-LC) method for determination of valsartan, applied to investigate bioequivalence of two valsartan tablets in Chinese volunteers under fasting condition. A full automatic 2D-HPLC system was used to quantify valsartan in human plasma. The analytes were extracted by protein precipitation, using telmisartan as internal standard. The analytical method was applied in a randomized, crossover bioequivalence study of valsartan tablets; the study enrolled 18 Chinese volunteers (12 were men and 6 were women). The subjects received a single 160-mg dose of test or reference preparation with 7-days of washout under fasting state. Plasma samples were collected, pharmacokinetic parameters were obtained and the bioequivalence was evaluated. The calibration range was 9.2 - 4213.8 ng×mL-1. Inter- and intraprecision was less than 7.0%, and accuracies ranged from 99.5 to 103.8%. The extraction recovery for valsartan varied between 89.3 and 97.8%, and the stability in all conditions was excellent. The 90% CI of AUC0→36h and Cmax were 96.5 - 109.4% and 94.2 - 108.6%, respectively. The relative bioavailability was 103.9 ± 15.7%. No gender difference was observed in pharmacokinetic parameters. A sensitive 2D-HPLC method was established for the estimation of valsartan in human plasma and successfully applied in a bioequivalence study of valsartan, which suggests that these two formulations can be assumed to be bioequivalent.
.

  17. Bioequivalence of diclofenac sodium 2% and 1.5% topical solutions relative to oral diclofenac sodium in healthy volunteers.

    Science.gov (United States)

    Holt, Robert J; Taiwo, Tolu; Kent, Jeffrey D

    2015-08-01

    Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption. We conducted randomized, crossover studies that compared the pharmacokinetics (PK), bioequivalence and safety of topical diclofenac sodium 2% twice daily (BID), diclofenac sodium 1.5% four times daily (QID) and oral diclofenac sodium in healthy subjects. The results of three bioequivalence studies are reviewed. Healthy adult subjects (n = 76) applied topical diclofenac sodium 2% solution (40.4 mg/2 mL) BID; or 1.5% solution (19.3 mg/40 drops) QID to each knee for 7.5 consecutive days separated by a washout period. Subjects (n = 22) in one study also received oral diclofenac sodium 75 mg BID for 7.5 days. Plasma diclofenac concentrations were determined from serial blood samples collected on Days 1 and 8 (steady state), and diclofenac PK parameters were estimated by noncompartmental methods. The studies demonstrated comparable bioequivalence between the 2% and 1.5% topical solutions as well as lower systemic exposure compared to oral dosing (approximately 93% less). Daily systemic exposure was comparable between the two formulations with only a 12% difference in the AUCss(0-24) (p = 0.140). Furthermore, both topical solutions demonstrated delayed elimination with a t(1/2) of 4- to 6-fold longer, as compared to oral diclofenac. The 2% solution provided more consistent dosing relative to the 1.5% solution when comparing AUCss(0-24) and Cmaxss across studies. Mild application site reactions were the most common treatment-emergent adverse event reported with topical diclofenac. The steady-state PK profile of topical diclofenac 2% solution administered BID is similar to that of the 1.5% solution administered QID. Systemic exposure to diclofenac is substantially lower after topical application as compared to oral administration. (Study 2 was registered with ClinicalTrials.gov; NCT01202799; https

  18. The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.

    Science.gov (United States)

    Ölçer, A; Ölçer, M; İnce, I; Karasulu, E

    2016-03-01

    Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

  19. Bioequivalent UV detectors based on cholesteric liquid crystals: effects of spectral composition and quantitative account for intensity of UV radiation

    Science.gov (United States)

    Lisetski, Longin N.; Panikarskaya, Valentina D.; Kasyan, Natalya A.; Grishchenko, Leonid V.; Terenetskaya, Irina P.

    2005-11-01

    Response of cholesteric sensor materials to biologically active UV radiation has been studied. The sensor mixture comprised a cholesteric liquid crystalline matrix doped with provitamin D, and changes in the maximum selective reflection wavelength λ max caused by the photochemical reaction of provitamin D --> vitamin D transformation were recorded. Using a UV source (DRT-240 lamp) calibrated accounting for the specific irradiation geometry, λ max shifts were obtained as function of UV illuminance dose (in J/cm2). Using a set of optical filters cutting off specified parts of the provitamin D absorption spectrum, effects of the spectral composition of UV radiation upon the response characteristics of sensor were determined. The results obtained support our earlier considerations of the developed sensor material as "bioequivalent".

  20. Pharmacokinetic properties and bioequivalence of two irbesartan/ hydrochlorothiazide fixed-dose combination tablets in healthy male Chinese volunteers.

    Science.gov (United States)

    Liu, Jian; Wu, Lihua; Hu, Xingjiang; Wu, Guolan; Zheng, Yunliang; Zhou, Huili; Zhai, You; Zhu, Meixiang; ShenTu, Jianzhong

    2015-07-01

    The aim of the present study was to compare the pharmacokinetic profiles between a new generic and a branded reference formulation of irbesartan/ hydrochlorothiazide FDC tablets, and to assess the bioequivalence of the two products in healthy Chinese male volunteers. 24 male healthy volunteers participated in the open-label, single-dose, randomized-sequence, 2-way crossover study. Eligible subjects were randomly assigned (1:1) to receive a single 300/12.5-mg dose of either the test or reference formulation followed by a 1-week washout. Blood samples were obtained before (0 hours) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours after dosing. Plasma concentrations of irbesartan and hydrochlorothiazide were analyzed by two separate validated liquid chromatography/tandem mass spectrometric (LC-MS/MS) methods. For irbesartan, the 90% confidence intervals (CIs) of AUC0-t, AUC0-∞, and Cmax were 103.27-116.71%, 105.01-121.47%, and 84.15-96.88%, respectively. For hydrochlorothiazide, the 90% CIs of AUC0-t, AUC0-∞, and Cmax were 96.11-109.02%, 95.15-107.35%, and 91.66-101.40%, respectively. A total of 3 mild AEs were reported in 3 subjects (12.5%). In this study, a single dose (300/12.5-mg) of the test formulation of irbesartan and hydrochlorothiazide FDC tablet in fasting healthy Chinese male volunteers met WHO's and China's FDA regulatory criteria for assumption of bioequivalence to the reference formulation based on AUC and Cmax. Both formulations were well tolerated.

  1. Plug-In Hybrid Electric Vehicle Value Proposition Study: Phase 1, Task 3: Technical Requirements and Procedure for Evaluation of One Scenario

    Energy Technology Data Exchange (ETDEWEB)

    Sikes, Karen R [ORNL; Hinds, Shaun [Sentech, Inc.; Hadley, Stanton W [ORNL; McGill, Ralph N [ORNL; Markel, Lawrence C [ORNL; Ziegler, Richard E [ORNL; Smith, David E [ORNL; Smith, Richard L [ORNL; Greene, David L [ORNL; Brooks, Daniel L [ORNL; Wiegman, Herman [GE Global Research; Miller, Nicholas [GE; Marano, Dr. Vincenzo [Ohio State University

    2008-07-01

    In Task 2, the project team designed the Phase 1 case study to represent the 'baseline' plug-in hybrid electric vehicle (PHEV) fleet of 2030 that investigates the effects of seventeen (17) value propositions (see Table 1 for complete list). By creating a 'baseline' scenario, a consistent set of assumptions and model parameters can be established for use in more elaborate Phase 2 case studies. The project team chose southern California as the Phase 1 case study location because the economic, environmental, social, and regulatory conditions are conducive to the advantages of PHEVs. Assuming steady growth of PHEV sales over the next two decades, PHEVs are postulated to comprise approximately 10% of the area's private vehicles (about 1,000,000 vehicles) in 2030. New PHEV models introduced in 2030 are anticipated to contain lithium-ion batteries and be classified by a blended mileage description (e.g., 100 mpg, 150 mpg) that demonstrates a battery size equivalence of a PHEV-30. Task 3 includes the determination of data, models, and analysis procedures required to evaluate the Phase 1 case study scenario. Some existing models have been adapted to accommodate the analysis of the business model and establish relationships between costs and value to the respective consumers. Other data, such as the anticipated California generation mix and southern California drive cycles, have also been gathered for use as inputs. The collection of models that encompasses the technical, economic, and financial aspects of Phase 1 analysis has been chosen and is described in this deliverable. The role of PHEV owners, utilities (distribution systems, generators, independent system operators (ISO), aggregators, or regional transmission operators (RTO)), facility owners, financing institutions, and other third parties are also defined.

  2. Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

    Science.gov (United States)

    Hu, Danqing; Flick, Randall P; Zaccariello, Michael J; Colligan, Robert C; Katusic, Slavica K; Schroeder, Darrell R; Hanson, Andrew C; Buenvenida, Shonie L; Gleich, Stephen J; Wilder, Robert T; Sprung, Juraj; Warner, David O

    2017-08-01

    Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes. A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models. For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability. These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

  3. Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects

    Directory of Open Access Journals (Sweden)

    Lee SY

    2015-06-01

    Full Text Available Soo-Yun Lee,1 Jung-Ryul Kim,2,3 Jin Ah Jung,4 Wooseong Huh,2,5 Mi Young Bahng,6 Jae-Wook Ko1,2 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; 2Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea; 3Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; 4Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 6Dong-A ST Co., Ltd., Seoul, Republic of Korea Abstract: A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg. Keywords: amlodipine orotate, amlodipine besylate, olmesartan medoxomil, fixed-dose combination, bioequivalence

  4. Postoperative pain medication requirements in patients undergoing computer-assisted (“Robotic”) and standard laparoscopic procedures for newly diagnosed endometrial cancer.

    Science.gov (United States)

    Leitao, Mario M; Malhotra, Vivek; Briscoe, Gabriel; Suidan, Rudy; Dholakiya, Priyal; Santos, Kevin; Jewell, Elizabeth L; Brown, Carol L; Sonoda, Yukio; Abu-Rustum, Nadeem R; Barakat, Richard R; Gardner, Ginger J

    2013-10-01

    patients who had undergone an RBT hysterectomy compared to a standard total LSC hysterectomy for benign indications.13 A recent cost analysis suggested that patients experienced less pain and required less pain medication use after RBT procedures compared to LSC for endometrial cancer.14 Based on these reports, we sought to analyze postoperative pain and the use of pain medication in patients undergoing RBT compared to standard transperitoneal LSC procedures for newly diagnosed endometrial cancer during a concurrent time period. Of note, current RBT surgery is not truly robotic in that it is not autonomous. A more appropriate term is “computer-assisted surgery,” but to satisfy current convention, we refer to it as “robotic surgery” in this manuscript.

  5. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  6. A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults.

    Science.gov (United States)

    Sikes, Carolyn; Stark, Jeffrey G; McMahen, Russ; Engelking, Dorothy

    2017-11-01

    The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d- and l-amphetamine concentrations, and pharmacokinetic parameters C max , AUC 0-5 , AUC 5-last , and AUC inf were calculated to determine bioequivalence. Safety was monitored throughout the study. The 90% confidence intervals (CIs) for the log-transformed C max , AUC 0-5 , AUC 5-last , and AUC inf fell within the accepted 80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The most common adverse events were nausea and decreased appetite. AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

  7. Human factoring administrative procedures

    International Nuclear Information System (INIS)

    Grider, D.A.; Sturdivant, M.H.

    1991-01-01

    In nonnuclear business, administrative procedures bring to mind such mundane topics as filing correspondence and scheduling vacation time. In the nuclear industry, on the other hand, administrative procedures play a vital role in assuring the safe operation of a facility. For some time now, industry focus has been on improving technical procedures. Significant efforts are under way to produce technical procedure requires that a validated technical, regulatory, and administrative basis be developed and that the technical process be established for each procedure. Producing usable technical procedures requires that procedure presentation be engineered to the same human factors principles used in control room design. The vital safety role of administrative procedures requires that they be just as sound, just a rigorously formulated, and documented as technical procedures. Procedure programs at the Tennessee Valley Authority and at Boston Edison's Pilgrim Station demonstrate that human factors engineering techniques can be applied effectively to technical procedures. With a few modifications, those same techniques can be used to produce more effective administrative procedures. Efforts are under way at the US Department of Energy Nuclear Weapons Complex and at some utilities (Boston Edison, for instance) to apply human factors engineering to administrative procedures: The techniques being adapted include the following

  8. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

    Science.gov (United States)

    Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

    2018-01-01

    A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to

  9. Bioequivalence of a biosimilar enoxaparin sodium to Clexane®after single 100 mg subcutaneous dose: results of a randomized, double-blind, crossover study in healthy volunteers.

    Science.gov (United States)

    Martínez González, Javier; Monreal, Mayte; Ayani Almagia, Ignacio; Llaudó Garín, Jordi; Ochoa Díaz de Monasterioguren, Lourdes; Gutierro Adúriz, Ibón

    2018-01-01

    To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence of a biosimilar enoxaparin to the reference drug, and to assess its safety and tolerability in healthy volunteers. A randomized, double-blind, crossover, 2-sequence, single-dose study was conducted in healthy volunteers of both sexes. Participants were sequentially and randomly administered single subcutaneous injections of enoxaparin 100 mg manufactured by Rovi (test; Madrid, Spain) and Clexane ® (enoxaparin 100 mg manufactured by Sanofi, reference) separated by a 1-week washout period. The primary PK/PD variables were maximum activity (A max ) and area under the effect curve from time 0 to the last measured activity (T) (AUEC 0-T ) and AUEC from time 0 to infinity (AUEC 0-inf ) of anti-FXa activity, and A max and AUEC 0-T of anti-FIIa activity. Secondary variables were A max and AUEC 0-T , AUEC 0-inf of tissue factor pathway inhibitor, and the ratio of AUEC 0-T anti-FXa to anti-FIIa activity. Biosimilarity would be shown when the 95% CI of the ratio of geometric least squares means (95% CI RGLSMs) of primary PK/PD parameters fell within the standard range of bioequivalence, ie, 80%-125%. The study sample consisted of 46 volunteers (33 males) aged 18-44 years and with body mass index ranging from 19.0 to 31.1 kg/m 2 . Three subjects did not complete the study. The curves of anti-FXa, anti-FIIa and tissue factor pathway inhibitor activities corresponding to administration of the test and reference products were comparable. The 95% CI RGLSMs of A max , AUEC 0-T and AUEC 0-inf for anti-FXa activity were 94.6%-105.9%, 99.8%-108.0% and 100.0%-108.6% respectively; A max and AUEC 0-T for anti-FIIa activity were 94.7%-112.6% and 90.9%-117.9% respectively. In addition, the 95% CI RGLSMs of all secondary variables fell within the range 80%-125%. The incidence and types of adverse events after administration of the test and reference drugs were similar. The results conclusively showed that the enoxaparin

  10. Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency.

    Science.gov (United States)

    Barker, Alan F; Campos, Michael A; Brantly, Mark L; Stocks, James M; Sandhaus, Robert A; Lee, Douglas; Steinmann, Kimberly; Lin, Jiang; Sorrells, Susan

    2017-12-01

    This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha 1 -proteinase inhibitor, Liquid Alpha 1 -PI, compared with the Lyophilized Alpha 1 -PI formulation (Prolastin®-C), for augmentation therapy in patients with alpha 1 -antitrypsin deficiency (AATD). In this double-blind, randomized, 20-week crossover study, 32 subjects with AATD were randomized to receive 8 weekly infusions of 60 mg/kg of Liquid Alpha 1 -PI or Lyophilized Alpha 1 -PI. Serial blood samples were drawn for 7 days after the last dose followed by 8 weeks of the alternative treatment. The primary endpoint was bioequivalence at steady state, as measured by area under the concentration versus time curve from 0 to 7 days (AUC 0-7 days ) postdose using an antigenic content assay. Bioequivalence was defined as 90% confidence interval (CI) for the ratio of the geometric least squares (LS) mean of AUC 0-7 days for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha 1 -PI concentration versus time curves for both formulations were superimposable. Mean AUC 0-7 days was 20 320 versus 19 838 mg × h/dl for Liquid Alpha 1 -PI and Lyophilized Alpha 1 -PI, respectively. The LS mean ratio of AUC 0-7 days (90% CI) for Liquid Alpha 1 -PI versus Lyophilized Alpha 1 -PI was 1.05 (1.03-1.08), indicating bioequivalence. Liquid Alpha 1 -PI was well tolerated and adverse events were consistent with Lyophilized Alpha 1 -PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha 1 -PI is bioequivalent to Lyophilized Alpha 1 -PI, with a similar safety profile. The liquid formulation would eliminate the need for reconstitution and shorten preparation time for patients receiving augmentation therapy for AATD.

  11. The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

    Science.gov (United States)

    Tsume, Yasuhiro; Amidon, Gordon L

    2010-08-02

    The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

  12. Bioequivalence study of two formulations of flupirtine maleate capsules in healthy male Chinese volunteers under fasting and fed conditions

    Directory of Open Access Journals (Sweden)

    Liu YF

    2017-12-01

    Full Text Available Yanfang Liu, Hua Huo, Zhibo Zhao, Wenli Hu, Yujia Sun, Yunbiao Tang Technical Center for Clinical Pharmacy, Department of Drug Clinical Trail Management Agency, General Hospital of Shenyang Military Area Command, Shenyang, China Aim: This study developed a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine the concentrations of flupirtine and its major active metabolite D-13223 in human plasma in order to assess the bioequivalence (BE of two flupirtine maleate capsules among healthy male Chinese volunteers under fasting and fed conditions. Materials and methods: There were two single-center, randomized, single-dose, open-label, laboratory-blinded, two-period, cross-over studies which included 24 healthy male Chinese volunteers under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 48 h after dosing. The concentrations of flupirtine and its major active metabolite D-13223 in plasma samples were determined by a validated method, that is, high-performance liquid chromatography coupled with a tandem mass spectrometry detector. Pharmacokinetic metrics of area from time zero to the last measurable concentration (AUC0-t, area under the plasma concentration–time curve from administration to infinite time (AUC0-∞, and Cmax were used for BE assessment. Results: Forty-eight healthy volunteers who met the criteria were enrolled and completed the study. According to the observation of vital signs and laboratory measurement, no volunteers had any adverse reactions. Under fasting condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 103.0% (98.1%–108.2% for AUC0-t, 102.9% (98.2%–107.9% for AUC0-∞, and 97.0% (85.9%–109.5% for Cmax. Under fed condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 101.7% (98.4%–105.1% for AUC0-t, 101.6% (98.5%–104.8% for AUC0-∞, and 103.5% (94.7%

  13. Procedures Manual: A Guide to Uniform Grant and Contract Management Standards and The Common Rule for Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments.

    Science.gov (United States)

    Conable, Sharon R.

    This manual has been compiled to provide consistent grant application and administrative procedures for state agencies which award grants or contracts to local governments. It provides a conceptual framework of information concerning the reporting, financial, contractual, and auditing requirements for recipients of Texas State Library grants…

  14. The Fundamental Right to Public Security and the Untermassverbot Principle: A Required Review of The Article #152 of the Brazilian Procedural Criminal Code

    Directory of Open Access Journals (Sweden)

    Marcial Duarte Coêlho

    2017-02-01

    Full Text Available The increasing of violence in Brazil affects the fundamental right to public security. When the State does not sufficiently protects a fundamental right there is a violation of the so-called untermassverbot principle. This paper aims to explore the interpretation of the article #152 of the brazilian procedural criminal code under the untermassverbot principle. The traditional interpretation understands that the criminal procedure will be stopped, but the prescription penal period is not equally interrupted. It is proposed a new reading of that article, under the approaches of the proportionality principle and the integral penal guaranteeism.

  15. Operating characteristics of a partial-block randomized crossover bioequivalence study for dutasteride, a drug with a long half-life: investigation through simulation and comparison with final results.

    Science.gov (United States)

    Cai, Gengqian; Thiessen, Jake J; Baidoo, Charlotte A; Fossler, Michael J

    2010-10-01

    Studies to establish bioequivalence (BE) of a drug are important elements in support of drug applications. A typical BE study is conducted as a single dose, randomized, 2-period crossover design. For drugs with long half lives (≥ 48 hours) and evaluation of multiple BE objectives in 1 trial, this design may not be adequate. A parallel design may then be a more appropriate choice. However, parallel designs require increased sample size, which can become substantial. One option that is a compromise between the complete randomized block design and the parallel design is a partial-block crossover design. This approach came about during the development of a combination of dutasteride and tamsulosin. Previous experience with performing single-dose dutasteride studies suggested that 28 days of washout is needed between treatments because of its half-life of 7-9 days. Simulations were performed to assess the operating characteristics of this design using a previously developed PK model. Four scenarios were developed, and each scenario was simulated 500 times. The results showed that this design demonstrated acceptable consumer and producer risk. Partial-block crossover designs should be considered for studies when the half-life of the drug is long and there are more than 2 periods.

  16. Quantification of strontium in human serum by ICP-MS using alternate analyte-free matrix and its application to a pilot bioequivalence study of two strontium ranelate oral formulations in healthy Chinese subjects.

    Science.gov (United States)

    Zhang, Dan; Wang, Xiaolin; Liu, Man; Zhang, Lina; Deng, Ming; Liu, Huichen

    2015-01-01

    A rapid, sensitive and accurate ICP-MS method using alternate analyte-free matrix for calibration standards preparation and a rapid direct dilution procedure for sample preparation was developed and validated for the quantification of exogenous strontium (Sr) from the drug in human serum. Serum was prepared by direct dilution (1:29, v/v) in an acidic solution consisting of nitric acid (0.1%) and germanium (Ge) added as internal standard (IS), to obtain simple and high-throughput preparation procedure with minimized matrix effect, and good repeatability. ICP-MS analysis was performed using collision cell technology (CCT) mode. Alternate matrix method by using distilled water as an alternate analyte-free matrix for the preparation of calibration standards (CS) was used to avoid the influence of endogenous Sr in serum on the quantification. The method was validated in terms of selectivity, carry-over, matrix effects, lower limit of quantification (LLOQ), linearity, precision and accuracy, and stability. Instrumental linearity was verified in the range of 1.00-500ng/mL, corresponding to a concentration range of 0.0300-15.0μg/mL in 50μL sample of serum matrix and alternate matrix. Intra- and inter-day precision as relative standard deviation (RSD) were less than 8.0% and accuracy as relative error (RE) was within ±3.0%. The method allowed a high sample throughput, and was sensitive and accurate enough for a pilot bioequivalence study in healthy male Chinese subjects following single oral administration of two strontium ranelate formulations containing 2g strontium ranelate. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. LC–MS/MS assay for olanzapine in human plasma and its application to a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Dinesh S. Patel

    2012-10-01

    Full Text Available This paper describes a selective and sensitive assay for the determination of olanzapine (OLZ in human plasma based on liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analyte and quetiapine as internal standard (IS were extracted from 200 μL plasma via solid phase extraction on Waters Oasis HLB cartridges. Chromatographic separation was achieved on an ACE 5C18-300 column (100 mm×4.6 mm, 5 μm under isocratic conditions in a run time of 3.5 min. Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring (MRM of the transitions at m/z 313/256 for OLZ and m/z 384/253 for the IS. The assay was linear in the range 0.10–40.0 ng/mL with a lower limit of quantitation and limit of detection of 0.10 and 0.012 ng/mL, respectively. Intra- and inter-day precision (as coefficient of variation and relative recovery were 90%, respectively. The method was successfully applied to a bioequivalence study of 5 and 10 mg OLZ disintegrating tablets in 40 healthy Indian males with reproducibility by incurred sample reanalysis in the range −7.43 to 8.07%.

  18. Developing policies and procedures.

    Science.gov (United States)

    Randolph, Susan A

    2006-11-01

    The development of policies and procedures is an integral part of the occupational health nurse's role. Policies and procedures serve as the foundation for the occupational health service and are based on its vision, mission, culture, and values. The design and layout selected for the policies and procedures should be simple, consistent, and easy to use. The same format should be used for all existing and new policies and procedures. Policies and procedures should be reviewed periodically based on a specified time frame (i.e., annually). However, some policies may require a more frequent review if they involve rapidly changing external standards, ethical issues, or emerging exposures.

  19. Procedural Issues regarding the Audit of the Management and Control of EU Funds, in Terms of Specific Key Requirements of the New Funding Period 2014 - 2020

    Directory of Open Access Journals (Sweden)

    Stelian Selișteanu

    2016-11-01

    Full Text Available In practice, planning the audit of management and control for each operational program and for the whole programming period, will perform during substantiation audit strategy, based on analysis and risk assessment, made at the entities involved in implementing the operational program. In what follows, we propose an assessment guidelines for the 2014- 2020 programming period, especially in terms of explanation addressed key requirements that must be used, explaining the evaluation criteria for each key requirement, providing guidance for drawing conclusions for each key requirement by each authority and finally making recommendations for establishing general conclusions regarding the management and control.

  20. 21 CFR 320.27 - Guidelines on the design of a multiple-dose in vivo bioavailability study.

    Science.gov (United States)

    2010-04-01

    ... vivo bioavailability study. 320.27 Section 320.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.27...

  1. 21 CFR 320.38 - Retention of bioavailability samples.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Retention of bioavailability samples. 320.38... (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.38 Retention of bioavailability samples...

  2. Harmine treatment enhances short-term memory in old rats: Dissociation of cognition and the ability to perform the procedural requirements of maze testing.

    Science.gov (United States)

    Mennenga, Sarah E; Gerson, Julia E; Dunckley, Travis; Bimonte-Nelson, Heather A

    2015-01-01

    Harmine is a naturally occurring monoamine oxidase inhibitor that has recently been shown to selectively inhibit the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A). We investigated the cognitive effects of 1mg (low) Harmine and 5mg (high) Harmine using the delayed-match-to-sample (DMS) asymmetrical 3-choice water maze task to evaluate spatial working and recent memory, and the Morris water maze task (MM) to test spatial reference memory. Animals were also tested on the visible platform task, a water-escape task with the same motor, motivational, and reinforcement components as the other tasks used to evaluate cognition, but differing in its greater simplicity and that the platform was visible above the surface of the water. A subset of the Harmine-high treated animals showed clear motor impairments on all behavioral tasks, and the visible platform task confirmed a lack of competence to perform the procedural components of water maze testing. After excluding animals from the high dose group that could not perform the procedural components of a swim task, it was revealed that both high- and low-dose treatment with Harmine enhanced performance on the latter portion of DMS testing, but had no effect on MM performance. Thus, this study demonstrates the importance of confirming motor and visual competence when studying animal cognition, and verifies the one-day visible platform task as a reliable measure of ability to perform the procedural components necessary for completion of a swim task. Copyright © 2014. Published by Elsevier Inc.

  3. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  4. Bioequivalence of lamotrigine 50-mg tablets in healthy male volunteers: a randomized, single-dose, 2-period, 2-sequence crossover study.

    Science.gov (United States)

    Perez-Lloret, S; Olmos, L; de Mena, F; Pieczanski, P; Rodriguez Moncalvo, J J

    2012-10-01

    OBEJCTIVE: To compare the bioavailability of two 50-mg lamotrigine dispersible tablet formulations (Epilepax®, Ivax-TEVA Argentina Laboratories, Argentina, as a test formulation, and Lamictal®, GlaxoSmithKline, UK, as a reference formulation) in 24 healthy male volunteers. This study was a randomized, 2-period, 2-sequence crossover design that was open for subjects and investigators, but blind for the bioanalytical lab. Serum samples were obtained over a 120-h interval. A 9-day wash-out period was allowed between treatments. The concentrations of lamotrigine were analyzed by high-performance liquid chromatography followed by ultraviolet-visible detection. Lamotrigine time-concentrations curves were obtained and the following pharmacokinetic parameters were calculated: AUC0-t, AUC0-inf and Cmax. Bioequivalence was declared if the 90% confidence interval (CI) of the mean test/reference ratios for AUC0-t, AUC0-inf and Cmax were within 80.00-125.00%. The geometric mean and respective 90% CI of test/reference percent ratios were 100.83% (92.53-107.88%) for AUC0-t, 99.91% (93.79-108.40%) for AUC0-inf, and 95.62% (90.91-100.57%) for Cmax. No serious adverse events were observed. 1 patient reported a mild rash following the administration of each formulation. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in this sample of fasting healthy volunteers. These results suggest that bioequivalence studies evaluating 50-mg doses of Lamotrigine are feasible and recommended, since such doses may minimize the risk of severe rash or Stevens-Johnson Syndrome. This study was registered at the Argentinean Clinical Trials National Registry (www.anmat.gov.ar), No 1666/2008. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Management of patients taking antiplatelet or anticoagulant medication requiring invasive breast procedures: United Kingdom survey of radiologists' and surgeons' current practice

    International Nuclear Information System (INIS)

    Pritchard, M.G.; Townend, J.N.; Lester, W.A.; England, D.W.; Kearins, O.; Bradley, S.A.

    2008-01-01

    Aim: To determine the current practice in the UK National Health Service Breast Screening Programme for invasive diagnostic procedures and surgery in patients taking anticoagulant and antiplatelet medication. Materials and methods: Lead radiologists and surgeons at each breast screening service were surveyed to determine current practice. One hundred and five respondents provided information regarding their services, protocols, and willingness to proceed with combinations of procedures and anti-haemostatic medications. Results: Between units there was wide variation in practice. Within 21 services providing more than one response, 10 (48%) disagreed on whether protocols existed. Decisions to perform biopsies were unrelated to professional group. The taking of a drug history was variable. Surgeons reported more adverse effects than radiologists [21 (48%) versus 12 (26%)], but no difference in self-assessment of knowledge. Conclusion: Both radiologists and surgeons have expressed uncertainty about their understanding of anticoagulant and antiplatelet treatment. This is reflected in a wide range of practice. Guidance regarding the management of these patients is suggested

  6. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  7. Determination of levodopa in human plasma by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS: application to a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Heliana F. Martins

    2013-01-01

    Full Text Available A sensitive, accurate and simple method using HPLC-MS/MS was developed and validated for levodopa quantitation in human plasma. Analysis was achieved on a pursuit® C18 analytical column (5 µm; 150 x 4.6 mm i.d. using a mobile phase (methanol and water , 90:10, v/v containing formic acid 0.5% v/v, after extracting the samples using a simple protein plasma precipitation with perchloric acid. The developed method was validated in accordance with ANVISA guidelines and was successfully applied to a bioequivalence study in 60 healthy volunteers demonstrating the feasibility and reliability of the proposed method.

  8. Rapid determination of telmisartan in human plasma by HPLC using a monolithic column with fluorescence detection and its application to a bioequivalence study.

    Science.gov (United States)

    Zhang, He; Jiang, Yunyun; Wen, Jun; Zhou, Tingting; Fan, Guorong; Wu, Yutian

    2009-11-01

    A rapid HPLC method using a monolithic column with fluorescence detection has been developed for determination of telmisartan in human plasma. Sample preparation was done by protein precipitation with acetonitrile and naproxen was used as IS. The compounds were detected by fluorescence detection, using an excitation wavelength of 300 nm and emission wavelength of 385 nm. Calibration curves of telmisartan were linear in the range of 1-200 ng/mL. The assay was high throughput, sensitive and precise, and it was successfully applied to a bioequivalence study of two formulations of telmisartan.

  9. Quantization Procedures

    International Nuclear Information System (INIS)

    Cabrera, J. A.; Martin, R.

    1976-01-01

    We present in this work a review of the conventional quantization procedure, the proposed by I.E. Segal and a new quantization procedure similar to this one for use in non linear problems. We apply this quantization procedures to different potentials and we obtain the appropriate equations of motion. It is shown that for the linear case the three procedures exposed are equivalent but for the non linear cases we obtain different equations of motion and different energy spectra. (Author) 16 refs

  10. Levothyroxine soft capsules demonstrate bioequivalent pharmacokinetic exposure with the European reference tablets in healthy volunteers under fasting conditions.

    Science.gov (United States)

    Al-Numani, Dina; Scarsi, Claudia; Ducharme, Murray P

    2016-02-01

    To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.

  11. Alternative Refractive Surgery Procedures

    Science.gov (United States)

    ... the epithelial cells. Once the epithelial flap is created and moved aside, the procedure is the same ... Sites EyeWiki International Society of Refractive Surgery * Required * First Name: * Last Name: Member ID: * Phone Number: * Email: * ...

  12. Bioequivalence of locally acting lozenges: Evaluation of critical in vivo parameters and first steps towards a bio-predictive in vitro test method.

    Science.gov (United States)

    Tietz, Katharina; Gutknecht, Sina I; Klein, Sandra

    2018-02-01

    Locally-acting lozenges are among the most common types of solid dosage forms applied in the oral cavity. Since no guidance on the in vitro demonstration of local bioequivalence is available, we wanted to develop a new bio-predictive test method for dissolution of lozenges based on a set of physiological parameters relevant to lozenge dissolution in the oral cavity. An in vivo sucking study determining the impact of different lozenge (candy) bases and flavours on sucking times, saliva osmolality and salivary flow rates was performed in 6 volunteers. In vivo sucking times were compared with in vitro dissolution times observed in experiments with official dissolution methods. In vitro dissolution times of all formulations were significantly longer than average in vivo sucking times (20-30 vs. hard palate during sucking. Results obtained in a first set of in vitro experiments came very close to those obtained in vivo. This novel in vitro approach is thus very promising in terms of predicting the bioequivalence of locally-acting lozenges. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Production Pathways and Separation Procedures for High-Diagnostic-Value Activation Species, Fission Products, and Actinides Required for Preparation of Realistic Synthetic Post-Detonation Nuclear Debris: Status Report and FY16 Project Plan

    Energy Technology Data Exchange (ETDEWEB)

    Faye, S. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Shaughnessy, D. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-08-19

    The objective of this project is to provide a comprehensive study on the production routes and chemical separation requirements for activation products, fission products, and actinides required for the creation of realistic post-detonation surrogate debris. Isotopes that have been prioritized by debris diagnosticians will be examined for their ability to be produced at existing irradiation sources, production rates, and availability of target materials, and chemical separation procedures required to rapidly remove the products from the bulk target matrix for subsequent addition into synthetic debris samples. The characteristics and implications of the irradiation facilities on the isotopes of interest will be addressed in addition to a summary of the isotopes that are already regularly produced. This is a planning document only.

  14. Improved national calculation procedures to assess energy requirements, nitrogen and VS excretions of dairy cows in the German emission model GAS-EM

    DEFF Research Database (Denmark)

    Dämmgen, Ulrich; Haenel, Hans-Dieter; Rösemann, Claus

    2009-01-01

    The calculation module for the assessment of feed intake and excretion rates of dairy cows in the German agricultural emission model GAS-EM is described in detail. The module includes the description of methane emissions from enteric fermentation as well as the assessment of volatile solids...... and (renal and faecal) nitrogen excretions responsible for carbon and nitrogen species emissions from manure management. Input parameters are milk yield and composition, weight and weight gain as well as feed properties. The model is based on the derivation of energy requirements and the limitation on dry...... for policy advice....

  15. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828 formulation and coadministered telmisartan and S-amlodipine in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kang WY

    2018-03-01

    Full Text Available Woo Youl Kang,1,2,* Sook Jin Seong,1,* Boram Ohk,1,2 Mi-Ri Gwon,1,3 Bo Kyung Kim,1,2 Sookie La,4 Hyun-Ju Kim,3 Seungil Cho,1 Young-Ran Yoon,1,2 Dong Heon Yang,5 Hae Won Lee1 1Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea; 3Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828 has been developed to increase convenience (as only one tablet is required per day and improve treatment compliance.Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t values of telmisartan were 522.29 ng/mL and 2,475.16 ng⋅h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng⋅h/mL for the individual agents

  16. Bioequivalence of a biosimilar enoxaparin sodium to Clexane® after single 100 mg subcutaneous dose: results of a randomized, double-blind, crossover study in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Martínez González J

    2018-03-01

    Full Text Available Javier Martínez González, Mayte Monreal, Ignacio Ayani Almagia, Jordi Llaudó Garín, Lourdes Ochoa Díaz de Monasterioguren, Ibón Gutierro Adúriz R&D Department, Laboratorios Farmacéuticos Rovi S.A., Madrid, Spain Purpose: To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD equivalence of a biosimilar enoxaparin to the reference drug, and to assess its safety and tolerability in healthy volunteers. Patients and methods: A randomized, double-blind, crossover, 2-sequence, single-dose study was conducted in healthy volunteers of both sexes. Participants were sequentially and randomly administered single subcutaneous injections of enoxaparin 100 mg manufactured by Rovi (test; Madrid, Spain and Clexane® (enoxaparin 100 mg manufactured by Sanofi, reference separated by a 1-week washout period. The primary PK/PD variables were maximum activity (Amax and area under the effect curve from time 0 to the last measured activity (T (AUEC0–T and AUEC from time 0 to infinity (AUEC0–inf of anti-FXa activity, and Amax and AUEC0–T of anti-FIIa activity. Secondary variables were Amax and AUEC0–T, AUEC0–inf of tissue factor pathway inhibitor, and the ratio of AUEC0–T anti-FXa to anti-FIIa activity. Biosimilarity would be shown when the 95% CI of the ratio of geometric least squares means (95% CI RGLSMs of primary PK/PD parameters fell within the standard range of bioequivalence, ie, 80%–125%.Results: The study sample consisted of 46 volunteers (33 males aged 18–44 years and with body mass index ranging from 19.0 to 31.1 kg/m2. Three subjects did not complete the study. The curves of anti-FXa, anti-FIIa and tissue factor pathway inhibitor activities corresponding to administration of the test and reference products were comparable. The 95% CI RGLSMs of Amax, AUEC0–T and AUEC0–inf for anti-FXa activity were 94.6%–105.9%, 99.8%–108.0% and 100.0%–108.6% respectively; Amax and AUEC0–T for anti-FIIa activity were 94.7%–112.6% and

  17. Tolerability, pharmacokinetics, and bioequivalence of the tablet and syrup formulations of lacosamide in plasma, saliva, and urine: saliva as a surrogate of pharmacokinetics in the central compartment.

    Science.gov (United States)

    Cawello, Willi; Bökens, Hilmar; Nickel, Brunhild; Andreas, Jens-Otto; Halabi, Atef

    2013-01-01

    To test for bioequivalence of 200 mg lacosamide oral tablet and syrup formulations. Additional objectives were to compare the pharmacokinetic profile of lacosamide in saliva and plasma, and to evaluate its tolerability. This open-label, randomized, two-way crossover trial was conducted in 16 healthy Caucasian male participants in Germany. The bioequivalence of 200 mg lacosamide tablet and syrup was evaluated using plasma to determine maximum measured concentration (C(max)) and area under the curve from zero to the last time point (AUC)(0-tz). Plasma and saliva samples for evaluation of pharmacokinetic parameters of lacosamide and the major metabolite O-desmethyl lacosamide (SPM 12809) were taken over 15 time points (0.5-72 h) and used to statistically compare bioavailability of the two. Urine samples were collected predose and over five time points (0-48 h) to evaluate the cumulative amount of unchanged drug and metabolite. Lacosamide median time to reach C(max) (t(max)) was 1 h for tablet and 0.5 h for syrup in plasma and saliva. Mean terminal half life (t(½)) for tablet and syrup was 12.5 and 12.4 h in plasma, and 13.1 and 13.3 h in saliva, respectively. Tablet and syrup mean plasma AUC(0-tz) was 84.5 and 83.3 μg/mL*h, respectively. Mean AUC(0-tz) in saliva was 93.2 μg/mL*h for tablet and syrup. Mean C(max) for tablet was 5.26 μg/mL in plasma and 5.63 μg/mL in saliva. Syrup mean C(max) was 5.14 and 8.32 μg/mL in plasma and saliva, respectively. Within 2 h of syrup administration, elevated lacosamide concentration in saliva compared to plasma was observed. The ratio of lacosamide syrup to tablet was 0.98 for C(max) and 0.99 for AUC(0-tz) in plasma, and 1.00 for AUC((0-tz)) in saliva; the 90% confidence intervals (CIs) for these parameters were within the range of 0.80-1.25, which meets accepted bioequivalence criteria. The syrup-to-tablet ratio for C(max) in saliva was 1.48, and the 90% CIs exceeded the accepted upper boundary for bioequivalence (1

  18. Bioequivalence and x-ray visibility of a radiopaque etonogestrel implant versus a non-radiopaque implant: a 3-year, randomized, double-blind study.

    Science.gov (United States)

    Schnabel, Peter; Merki-Feld, Gabriele S; Malvy, Alice; Duijkers, Ingrid; Mommers, Ellen; van den Heuvel, Michiel W

    2012-06-01

    The etonogestrel (ENG)-releasing implant is a subdermal progestogen-only contraceptive that provides coverage for up to 3 years. This long-acting hormonal contraceptive has been available in Europe since 1998 and in the US since 2006. To date, localization of non-palpable implants at insertion and before removal has been dependent on ultrasound or magnetic resonance imaging by an experienced clinician. To facilitate localization in rare cases of non-palpable implants using widely available equipment without the need for a specialist, a radiopaque ENG implant has been developed that is detectable by two-dimensional x-ray imaging. This study aimed to establish whether the radiopaque ENG implant is bioequivalent in situ compared with the original non-radiopaque ENG implant, and to assess x-ray visibility of the radiopaque ENG implant. This was a 3-year, randomized, double-blind, parallel-group study carried out in nine international clinical trial centres. Women aged 18-40 years at the time of screening, with menstrual cycles of a usual length of 24-35 days and a body mass index of between ≥18 and ≤29 kg/m(2) were included. Women were assigned to either the radiopaque or non-radiopaque ENG implant in a 1 : 1 ratio via a block randomization by centre. Bioequivalence testing was performed based on the peak ENG concentration (C(max)), and the area under the curve (AUC) for ENG at 6, 24 and 36 months (AUC(6 mo), AUC(24 mo) and AUC(36 mo)) after insertion. For this purpose, blood sampling for pharmacokinetic determination was performed prior to insertion and for up to 3 years afterwards. Bioequivalence was defined as the 90% confidence interval (CI) of the ratio radiopaque implant/non-radiopaque implant of the geometric means (GMR) within the acceptance range of 0.80-1.25. x-Ray visibility was assessed by two-dimensional x-ray imaging after insertion and before removal of the implant. The pharmacokinetic profiles of ENG indicated that the radiopaque and non

  19. Evaluation of two novel tablet formulations of artemether-lumefantrine (Coartem) for bioequivalence in a randomized, open-label, two-period study.

    Science.gov (United States)

    Lefèvre, Gilbert; Bhad, Prafulla; Jain, Jay Prakash; Kalluri, Sampath; Cheng, Yi; Dave, Hardik; Stein, Daniel S

    2013-09-08

    Artemether-lumefantrine (Coartem; AL) is a standard of care for malaria treatment as an oral six-dose regimen, given twice daily over three days with one to four tablets (20/120 mg) per dose, depending on patient body weight. In order to reduce the pill burden at each dose and potentially enhance compliance, two novel fixed-dose tablet formulations (80/480 mg and 60/360 mg) have been developed and tested in this study for bioequivalence with their respective number of standard tablets. A randomized, open-label, two-period, single-dose, within formulation crossover bioequivalence study comparing artemether and lumefantrine exposure between the novel 80/480 mg tablet and four standard tablets, and the novel 60/360 mg tablet and three standard tablets, was conducted in 120 healthy subjects under fed conditions. Artemether, dihydroartemisinin, and lumefantrine were measured in plasma by HPLC/UPLC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analyses. Adjusted geometric mean AUClast for artemether were 345 and 364 ng·h/mL (geometric mean ratio (GMR) 0.95; 90% CI 0.89-1.01) and for lumefantrine were 219 and 218 μg·h/mL (GMR 1.00; 90% CI 0.93-1.08) for 80/480 mg tablet versus four standard tablets, respectively. Corresponding Cmax for artemether were 96.8 and 99.7 ng/mL (GMR 0.97; 90% CI 0.89-1.06) and for lumefantrine were 8.42 and 8.71 μg/mL (GMR 0.97; 90% CI 0.89-1.05). For the 60/360 mg tablet versus three standard tablets, adjusted geometric mean AUClast for artemether were 235 and 231 ng·h/mL (GMR 1.02; 90% CI 0.94-1.10), and for lumefantrine were 160 and 180 μg·h/mL (GMR 0.89; 90% CI 0.83-0.96), respectively. Corresponding Cmax for artemether were 75.5 and 71.5 ng/mL (GMR 1.06; 90% CI 0.95-1.18), and for lumefantrine were 6.64 and 7.61 μg/mL (GMR 0.87; 90% CI 0.81-0.94), respectively. GMR for Cmax and AUClast for artemether and lumefantrine for all primary comparisons were within the bioequivalence acceptance criteria (0

  20. Pharmacokinetic properties and bioequivalence of two sulfadoxine/pyrimethamine fixed-dose combination tablets: a parallel-design study in healthy Chinese male volunteers.

    Science.gov (United States)

    Liu, Yan-Mei; Zhang, Kanyin E; Liu, Yun; Zhang, Hai-Chen; Song, Yun-Xiao; Pu, Hua-Hua; Lu, Chuan; Liu, Gang-Yi; Jia, Jing-Ying; Zheng, Qing-Si; Zhu, Jian-Min; Yu, Chen

    2012-11-01

    Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the long-acting portion of the antimalaria product Artecospe(®), coblister containing artesunate tablets plus sulfadoxine/pyrimethamine FDC tablets. This study was conducted to support the efficacy and tolerability of the sulfadoxine/pyrimethamine FDC tablet in the World Health Organization's (WHO) Prequalification of Medicines Programme, as well as to obtain marketing authorization in China. The aim of the present study was to compare the pharmacokinetic profiles between a new generic and the branded reference formulation of sulfadoxine/pyrimethamine FDC tablets, and to assess the bioequivalence of the 2 products in healthy Chinese volunteers. This single-dose, open-label, randomized, parallel-group study was conducted in healthy Chinese male volunteers who were randomly assigned (1:1) to receive a single 1500/75-mg dose (3 × 500/25-mg tablets) of either the test or reference formulation after a 12-hour overnight fast. Seventeen blood samples were obtained over a 168-hour interval, and plasma concentrations of sulfadoxine and pyrimethamine were determined by 2 separate validated liquid chromatography-isotopic dilution mass spectrometry methods. Pharmacokinetic properties (C(max), AUC(0-72), AUC(0-168), and T(max)) were calculated and analyzed statistically. The 2 formulations were to be considered bioequivalent if 90% CIs for the log-transformed ratios of C(max) and AUC(0-72) were within the predetermined bioequivalence range of 80% to 125%, in accordance with the guidelines of WHO and China's Food and Drug Administration (FDA). Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead ECGs, and subject interviews on adverse events (AEs). Forty-six healthy subjects completed the study. The mean values of sulfadoxine C(max) (183.07 and 165.15 mg/L), AUC(0-72) (11,036.52 and 10,536.78 mg/L/h), and AUC(0-168) (22,247.05 and 21,761.02 mg

  1. Quantas manobras são necessárias para abolir o nistagmo na vertigem posicional paroxística benigna? The number of procedures required to eliminate positioning nystagmus in benign paroxysmal positional vertigo

    Directory of Open Access Journals (Sweden)

    Ricardo Schaffeln Dorigueto

    2005-12-01

    selected according to each combination of canalithiasis or cupulolithiasis with semicircular canal involvement. Patients were treated by means of canalith repositioning procedures repeated weekly until the elimination of the positioning nystagmus. Analysis of Variance was used to verify differences between the variables. RESULTS: An average of 2.13 procedures (from 1 to 8 was needed to eliminate the positioning nystagmus. Canalithiasis required an average of 1.53 procedures, while cupulolithiasis needed 2.92 procedures (p=0.0002. An average of two procedures was needed to eliminate the positioning nystagmus in cases with posterior canal involvement, 2.39 procedures in cases with anterior canal involvement and 2.07 procedures in cases with lateral canal involvement (p=0.5213. CONCLUSIONS: From one to eight weekly canalith repositioning procedures were needed, with an average of two, to eliminate positioning nystagmus in benign paroxysmal positional vertigo. Cupulolithiasis requires a greater number of procedures than canalithiasis to eliminate positioning nystagmus. Semicircular canal involvement didn't influence the number of therapeutic maneuvers.

  2. Civil Procedure.

    Science.gov (United States)

    Byer, Robert

    1997-01-01

    Briefly reviews the historical development of civil procedure (the rules that dictate how a civil case can proceed through the courts) and identifies some of its main components. Discusses procedures such as subject matter jurisdiction, personal jurisdiction, venue, discovery, motions practice, pleadings, pretrial conference, and trials. (MJP)

  3. At-risk adolescents as experts in a new requirements elicitation procedure for the development of a smart phone psychoeducational trauma-informed care application.

    Science.gov (United States)

    Sockolow, Paulina; Schug, Seran; Zhu, Jichen; Smith, T J; Senathirajah, Yalini; Bloom, Sandra

    2017-01-01

    Adolescents from urban, socioeconomically disadvantaged communities of color encounter high rates of adverse childhood experiences. To address the resulting multidimensional problems, we developed an innovative approach, Experiential Participatory and Interactive Knowledge Elicitation (EPIKE), using remote experiential needs elicitation methods to generate design and content requirements for a mobile health (mHealth) psychoeducational intervention. At a community-based organization in a northeastern city, the research team developed EPIKE by incorporating elicitation of input on the graphics and conducting remotely recorded experiential meetings and iterative reviews of the design to produce an mHealth smartphone story application (app) prototype for the participants to critique. The 22 participants were 13- to 17-year-olds, predominantly African American and female, from underresourced communities. The four goals of the design process were attained: 1) story development from participant input; 2) needs-elicitation that reflected the patient-centered care approach; 3) interactive story game creation that accommodates the participants' emotional and cognitive developmental needs; 4) development of a game that adolescents can relate to and that which matches their comfort levels of emotional intensity. The EPIKE approach can be used successfully to identify the needs of adolescents across the digital divide to inform the design and development of mHealth apps.

  4. Proposal for geological site selection for L/ILW and HLW repositories. Statement of requirements, procedure and results. Technical report 08-03

    International Nuclear Information System (INIS)

    2008-10-01

    Important steps in the process of managing radioactive wastes have already been implemented in Switzerland. These include the handing and packaging of the waste, waste characterisation and documentation of waste inventories and interim storage along with associated transport. In terms of preparing for deep geological disposal, the necessary scientific and technical work is well advanced and the feasibility of constructing geological repositories that provide the required long-term safety has been successfully demonstrated for all waste types arising in Switzerland. Sufficient knowledge is available to allow the next steps in the selection of repository sites to be defined. The legal framework is also in place and organisational measures have been provided that will allow the tasks to be performed in the coming years to be implemented efficiently. The selection of geological siting regions and sites for repositories in Switzerland will be conducted in three stages. Stage 1 ends with the definition of geological siting regions within which the repository projects will be elaborated in more detail in stages 2 and 3. This report documents and justifies the siting proposals prepared by Nagra for the repositories for low- and intermediate-level waste (L/ILW) and high-level waste (HLW). Formulation of these proposals is conducted in five steps: 1) The waste inventory, which includes reserves for future developments, is allocated to the L/ILW and HLW repositories; 2) Based on this waste allocation, the second step involves defining the barrier and safety concepts for the two repositories. With a view to evaluating the geological siting possibilities, quantitative and qualitative guidelines and requirements on the geology are derived on the basis of these concepts. These relate to the time period to be considered, the space requirements for the repository, the properties of the host rock (depth, thickness, lateral extent, hydraulic conductivity), long-term stability

  5. Photodigitizing procedures

    Science.gov (United States)

    Kilgore, P. D.; Gottbrath, J. H.

    1984-02-01

    This report documents procedures and programs for efficiently running the Photo Digitizing System at the Naval Biodynamics Laboratory. Procedures have been tested and have been found to be effective. Any future acquisitions of programs or changes to current programs should be incorporated in these procedures. On-going research programs use high speed instrumentation cameras to record the motion of test subjects during biodynamic experiments. The films are digitized and the 3-dimensional motion is reconstructed and analyzed. Experimental research is performed to determine the effects of aircraft crashes, ship motion, vibration, aircraft ejection and parachute opening forces on the health and performance of Navy personnel.

  6. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Radicioni M

    2017-04-01

    Full Text Available Milko Radicioni,1 Chiara Castiglioni,1 Andrea Giori,2 Irma Cupone,3 Valeria Frangione,4 Stefano Rovati4 1CROSS Research S.A., Phase I Unit, Arzo, Switzerland; 2IBSA Farmaceutici Italia, Lodi, Italy; 3Bouty S.p.A., Strada Padana Superiore, Cassina De’ Pecchi, Italy; 4IBSA Institut Biochimique S.A., Pambio-Noranco, Switzerland Abstract: A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra® after single-dose administration to 53 healthy male volunteers (aged 18–51 years in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg

  7. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2015-09-01

    Full Text Available Abdel Naser Zaid,1 Murad N Abualhasan,1 David G Watson,2 Ayman Mousa,3 Nadia Ghazal,4 Rana Bustami5 1Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK; 3R&D Department, Avalon Pharma (Middle East Pharmaceutical Industries Co. Ltd., Riyadh, Kingdom of Saudi Arabia; 4Naratech Pharmaceutical Consultancy, 5Pharmaceutical Research Unit, Amman, Jordan Background: Montelukast (MT is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis.Objective: The aim of this study was to evaluate the bioequivalence (BE of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers.Methods: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products.Results: The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2 was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of

  8. Procedural semantic cities

    OpenAIRE

    Roglà Pujalt, Otger; Pelechano Gómez, Núria; Patow, Gustavo Ariel

    2017-01-01

    Procedural modeling of virtual cities has achieved high levels of realism with little effort from the user. One can rapidly obtain a large city using off-the-shelf software based on procedural techniques, such as the use of CGA. However in order to obtain realistic virtual cities it is necessary to include virtual humanoids that behave realistically adapting to such environment. The first step towards achieving this goal requires tagging the environment with semantics, which is a time consumi...

  9. Oculoplastic procedures

    Science.gov (United States)

    ... procedures may be done on the: Eyelids Eye sockets Eyebrows Cheeks Tear ducts Face or forehead These ... eyes. These lenses help protect your eyes and shield them from the bright lights of the surgical ...

  10. Radiation protection in medical research. Licensing requirement for the use of radiation and advice for the application procedure; Strahlenschutz in der medizinischen Forschung. Genehmigungsbeduerftigkeit von Strahlenanwendungen und Hinweise zum Antragsverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Minkov, V.; Klammer, H.; Brix, G. [Bundesamt fuer Strahlenschutz, Abteilung fuer medizinischen und beruflichen Strahlenschutz, Neuherberg (Germany)

    2017-07-15

    In Germany, persons who are to be exposed to radiation for medical research purposes are protected by a licensing requirement. However, there are considerable uncertainties on the part of the applicants as to whether licensing by the competent Federal Office for Radiation Protection is necessary, and regarding the choice of application procedure. The article provides explanatory notes and practical assistance for applicants and an outlook on the forthcoming new regulations concerning the law on radiation protection of persons in the field of medical research. Questions and typical mistakes in the application process were identified and evaluated. The qualified physicians involved in a study are responsible for deciding whether a license is required for the intended application of radiation. The decision can be guided by answering the key question whether the study participants would undergo the same exposures regarding type and extent if they had not taken part in the study. When physicians are still unsure about their decision, they can seek the advisory service provided by the professional medical societies. Certain groups of people are particularly protected through the prohibition or restriction of radiation exposure. A simplified licensing procedure is used for a proportion of diagnostic procedures involving radiation when all related requirements are met; otherwise, the regular licensing procedure should be used. The new radiation protection law, which will enter into force on the 31st of december 2018, provides a notification procedure in addition to deadlines for both the notification and the licensing procedures. In the article, the authors consider how eligible studies involving applications of radiation that are legally not admissible at present may be feasible in the future, while still ensuring a high protection level for study participants. (orig.) [German] Personen, bei denen Strahlenanwendungen zum Zweck der medizinischen Forschung durchgefuehrt

  11. A sensitive and robust lc-ms/ms method with monolithic column and electrospray ionization for the quantitation of efavirenz in human plasma: application to a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Danilo Cesar Galindo Bedor

    2011-01-01

    Full Text Available An LC-MS/MS method has been developed for the determination of efavirenz (EFZ in human plasma using hydrochlorothiazide as internal standard (I.S.. An ESI negative mode with multiple reaction-monitoring was used monitoring the transitions m/z 313.88→69.24 (EFZ and 296.02→204.76 (I.S.. Samples were extracted using liquid-liquid extraction. The total run time was 2.0 min. The separation was achieved with HPLC-RP using a monolithic column. The assay was linear in the concentration range of 100 - 5000 ng mL-1. The mean recovery was 83%. Intra- and inter-day precision were < 9.5% and < 8.9%, respectively and accuracy was in the range ± 8.33%. The method was successfully applied to a bioequivalence study.

  12. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    Science.gov (United States)

    Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

    2017-01-01

    A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

  13. Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers.

    Science.gov (United States)

    Weisfeld, Lori; Shu, Youyi; Shah, Tushar P

    2015-07-01

    Budesonide formoterol (BF) Spiromax® is a breath-actuated dry-powder inhaler designed to deliver similar combinations of budesonide and formoterol as Symbicort® Turbohaler®. We performed two studies to demonstrate pharmacokinetic (PK) equivalence of BF Spiromax with BF Turbohaler. Two single-center, open-label, randomized, 5-period crossover studies were performed. The first study compared BF Spiromax 160/4.5 μg with BF Turbohaler 200/6 μg, while the second study compared BF Spiromax 320/9 μg with BF Turbohaler 400/12 μg. All treatments were administered with and without charcoal. PK parameters were calculated by measuring plasma drug concentrations from blood samples taken pre-dose and up to 24 hours post-dose. In each study, 90 healthy volunteers were randomized. Bioequivalence of BF Spiromax with BF Turbohaler was demonstrated for budesonide and formoterol (AUC0-t and Cmax (90% confidence intervals of the geometric mean between-device ratios for both parameters were within the predefined range of 0.80-1.25 in both studies)). Equivalence was observed without use of charcoal (overall absorption post-inhalation) and with charcoal (pulmonary absorption). There were no major differences between treatments in tmax for either budesonide or formoterol. All study treatments were well tolerated (one treatment-emergent adverse event (TEAE) in the medium-dose study and four TEAEs in the high-dose study). These studies indicate that BF Spiromax (±charcoal block) is bioequivalent to BF Turbohaler with respect to the PK parameters assessed. Single doses of BF Spiromax were well tolerated; the overall safety profile of BF Spiromax and BF Turbohaler was similar.

  14. Randomized two-way cross-over bioequivalence study of two amoxicillin formulations and inter-ethnicity pharmacokinetic variation in healthy Malay volunteers.

    Science.gov (United States)

    Liew, Kai Bin; Loh, Gabriel Onn Kit; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2014-09-01

    The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations. Copyright © 2014 John Wiley & Sons, Ltd.

  15. The effect of food on the pharmacokinetic properties and bioequivalence of two formulations of pitavastatin calcium in healthy Chinese male subjects.

    Science.gov (United States)

    Shang, Dewei; Deng, Shuhua; Yao, Zhenhong; Wang, Zhanzhang; Ni, Xiaojia; Zhang, Ming; Hu, Jinqing; Lu, Haoyang; Zhu, Xiuqing; Huang, Wencan; Qiu, Chang; Wen, Yuguan

    2016-01-01

    1. Pitavastatin is an effective treatment for primary hyperlipidemia and mixed dyslipidemia. The aim of the present study was to investigate the effect of food on the pharmacokinetic properties and bioequivalence of the original, branded, formulation of pitavastatin calcium and a new generic formulation in healthy Chinese male subjects under fasting and fed conditions. 2. Under fasting and fed conditions, 90% CIs of the geometric mean of generic/branded AUC0-48 h ratios were 92.2-102.4%, 93.1-104.5%, the ratios of ln(AUC0-∞) were 92.6-103.7%, 93.2-103.5%, and ln(Cmax) ratios were 90.7-110.3%, 84.7-100.8%, respectively. The generic and branded formulations were bioequivalent in terms of rate and extent of absorption under both the conditions. The average values of AUC0-48 h, AUC0-∞ and Cmax decreased noticeably following a high-fat breakfast. Values for AUC0-48 h were 87.69% and 83.7%, values for AUC0-∞ were 87.5% and 84.6%, and values for Cmax were 45.0% and 50.4% in subjects given the generic and branded preparations, respectively. The absorption of pitavastatin calcium tablets was delayed following a high-fat meal, with Tmax increasing by up to 2.43-fold. 3. Both formulations were generally well tolerated, with no serious adverse reactions reported. The newly developed generic formulation may provide a reliable alternative to the branded tablets for patients with primary hyperlipidemia or mixed dyslipidemia.

  16. Improved simultaneous quantitation of candesartan and hydrochlorthiazide in human plasma by UPLC–MS/MS and its application in bioequivalence studies

    Directory of Open Access Journals (Sweden)

    Bhupinder Singh

    2014-04-01

    Full Text Available A validated ultra-performance liquid chromatography mass spectrometric method (UPLC–MS/MS was used for the simultaneous quantitation of candesartan (CN and hydrochlorothiazide (HCT in human plasma. The analysis was performed on UPLC–MS/MS system using turbo ion spray interface. Negative ions were measured in multiple reaction monitoring (MRM mode. The analytes were extracted using a liquid–liquid extraction (LLE method by using 0.1 mL of plasma volume. The lower limit of quantitation for CN and HCT was 1.00 ng/mL whereas the upper limit of quantitation was 499.15 ng/mL and 601.61 ng/mL for CN and HCT respectively. CN d4 and HCT-13Cd2 were used as the internal standards for CN and HCT respectively. The chromatography was achieved within 2.0 min run time using a C18 Phenomenex, Gemini NX (100 mm×4.6 mm, 5 µm column with organic mixture:buffer solution (80:20, v/v at a flow rate of 0.800 mL/min. The method has been successfully applied to establish the bioequivalence of candesartan cilexetil (CNC and HCT immediate release tablets with reference product in human subjects. Keywords: Candesartan cilexetil, Hydrochlorothiazide, UPLC–MS/MS, Bioequivalence, Candesartan cilexetil-hydrochlorothiazide (ATACAND HCT

  17. Bioequivalence studies for 2 different strengths of irbesartan/hydrochlorothiazide combination in healthy volunteers: 300/25 mg and 300/12.5 mg film-coated tablets.

    Science.gov (United States)

    Cánovas, M; Cabré, F; Polonio, F

    2014-05-01

    Two bioequivalence studies of irbesartan (CAS 138402-11-6) and hydrochlorothiazide (CAS 58-93-5) combination at 300/12.5 mg and 300/25 mg strengths were carried out in order to assess the bioequivalence of these film-coated tablet formulations in comparison with the marketed reference formulations.Both studies were performed with 30 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. In each study, test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 72 h following drug administration in case of irbesartan and up to 24 h in case of hydrochlorothiazide. Plasma concentrations of both analytes were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference).For both studies, the 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t [(irbesartan: 300/12.5 mgstrength: 95.33-111.74%. 300/25 mg strength: 91.27-103.93%) (hydrochlorothiazide: 300/12.5 mg strength: 99.63-107.50%. 300/25 mg strength: 95.72-102.24%)] and Cmax [(irbesartan: 300/12.5 mg strength: 98.73-115.03%. 300/25 mg strength: 97.27-112.12%) (hydrochlorothiazide: 300/12.5 mg strength: 97.34-112.06%. 300/25 mg strength: 93.29-106.38%)] were within the bio-equivalence acceptance range of 80-125%.According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that both test formulations are bioequivalent to the corresponding reference formulations. Overall, it was judged that both studies were conducted with a good tolerance of the subjects to study drugs. © Georg Thieme Verlag KG Stuttgart · New York.

  18. 12 CFR 575.13 - Procedural requirements.

    Science.gov (United States)

    2010-01-01

    ... Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY MUTUAL HOLDING COMPANIES... accountholder approval of a mutual holding company reorganization shall address in detail: (i) The reasons for the reorganization, including the relative advantages and disadvantages of undertaking the transaction...

  19. Environmental procedures

    International Nuclear Information System (INIS)

    1992-01-01

    The European Bank has pledged in its Agreement to place environmental management at the forefront of its operations to promote sustainable economic development in central and eastern Europe. The Bank's environmental policy is set out in the document titled, Environmental Management: The Bank's Policy Approach. This document, Environmental Procedures, presents the procedures which the European Bank has adopted to implement this policy approach with respect to its operations. The environmental procedures aim to: ensure that throughout the project approval process, those in positions of responsibility for approving projects are aware of the environmental implications of the project, and can take these into account when making decisions; avoid potential liabilities that could undermine the success of a project for its sponsors and the Bank; ensure that environmental costs are estimated along with other costs and liabilities; and identify opportunities for environmental enhancement associated with projects. The review of environmental aspects of projects is conducted by many Bank staff members throughout the project's life. This document defines the responsibilities of the people and groups involved in implementing the environmental procedures. Annexes contain Environmental Management: The Bank's Policy Approach, examples of environmental documentation for the project file and other ancillary information

  20. Anesthesia for radiologic procedures

    International Nuclear Information System (INIS)

    Forestner, J.E.

    1987-01-01

    Anesthetic techniques for neurodiagnostic studies and radiation therapy have been recently reviewed, but anesthetic involvement in thoracic and abdominal radiology has received little attention. Patient reactions to radiologic contrast media may be of concern to the anesthesiologist, who is often responsible for injecting these agents during diagnostic procedures, and thus is included in this discussion. Finally, the difficulties of administering anesthesia for magnetic resonance imaging (MRI) scans are outlined, in an effort to help anesthesiologist to anticipate problems with this new technologic development. Although there are very few indications for the use of general anesthesia for diagnostic radiologic studies in adults, most procedures performed with children, the mentally retarded, or the combative adult require either heavy sedation or general anesthesia. In selecting an anesthetic technique for a specific procedure, both the patient's disease process and the requirements of the radiologist must be carefully balanced

  1. Radiochemical procedures

    International Nuclear Information System (INIS)

    Lyon, W.S.

    1982-01-01

    The modern counting instrumentation has largely obviated the need for separation processes in the radiochemical analysis but problems in low-level radioactivity measurement, environmental-type analyses, and special situations caused in the last years a renaissance of the need for separation techniques. Most of the radiochemical procedures, based on the classic works of the Manhattan Project chemists of the 1940's, were published in the National Nuclear Energy Series (NNES). Improvements such as new solvent extraction and ion exchange separations have been added to these methods throughout the years. Recently the Los Alamos Group have reissued their collected Radiochemical Procedures containing a short summary and review of basic inorganic chemistry - 'Chemistry of the Elements on the Basis of Electronic Configuration'. (A.L.)

  2. Bioequivalence study between a fixed-dose single-pill formulation of nebivolol plus hydrochlorothiazide and separate formulations in healthy subjects using high-performance liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Vespasiano, Celso Francisco Pimentel; Laurito, Tiago Luders; Iwamoto, Renan Donomae; Moreno, Ronilson Agnaldo; Mendes, Gustavo D; De Nucci, Gilberto

    2017-05-01

    Systemic arterial hypertension is a major risk factor for cerebrovascular disease. Therefore, adequate control of blood pressure is of enormous importance. One of the many fixed-dose single-pill antihypertensive formulations available on the market is the combination of nebivolol and hydrochlorothiazide. The objective of this study was to develop two distinct high-performance liquid chromatography coupled to tandem mass spectrometry methods to simultaneously quantify nebivolol and hydrochlorothiazide in human plasma. The methods were employed in a bioequivalence study, the first assay involving a nebivolol fixed-dose single-pill formulation based on healthy Brazilian volunteers. Nebilet HCT™ (nebivolol 5 mg + hydrochlorothiazide 12.5 mg tablet, manufactured by Menarini) was the test formulation. The reference formulations were Nebilet™ (nebivolol 5 mg tablet, manufactured by Menarini) and Clorana™ (hydrochlorothiazide 25 mg tablet, manufactured by Sanofi). For both analytes, liquid-liquid extraction was employed for sample preparation and the chromatographic run time was 3.5 min. The limits of quantification validated were 0.02 ng/mL for nebivolol and 1 ng/mL for hydrochlorothiazide. Since the 90% CI for C max , AUC (0-last) and AUC (0-inf) individual test/reference ratios were within the 80-125% interval indicative of bioequivalence, it was concluded that Nebilet HCT™ is bioequivalent to Nebilet™ and Clorana™. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Material control assessment procedure

    International Nuclear Information System (INIS)

    Adams, R.W.; Spogen, L.R.

    1977-06-01

    The material control system assessment procedure being developed by the Lawrence Livermore Laboratory for the U.S. Nuclear Regulatory Commission is reviewed. It consists of five major sections: Target Identification, Adversary Sequence and Simuli Generation, Material Control System Response Determination, Safeguard System Outcome Determination, and Safeguard System Utility Determination. When adopted, this procedure will reduce safeguards licensing problems by providing compatibility with future performance based regulations, explicit evaluation rules and requirements, well-defined trade-off structures, and user-oriented and systematic evaluation and design tools

  4. Estudio de bioequivalencia de clonazepam, tabletas de 2 mg, en voluntarios sanos colombianos Bioequivalence study of clonazepam 2 mg tablets in colombian healthy volunteers

    Directory of Open Access Journals (Sweden)

    Victoria Eugenia Toro Pareja

    2007-08-01

    Full Text Available Con el fin de determinar la bioequivalencia de dos formulaciones de tabletas de 2 mg de clonazepam: Sedatril®/Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia como producto de prueba y Rivotril® (Roche Químicos e Farmacéuticas S. A., Río de Janeiro, Brasil, como producto de referencia, se realizó un estudio de bioequivalencia en 26 voluntarios sanos. Los productos de prueba y de referencia se administraron en condiciones de ayuno de acuerdo con un diseño cruzado aleatorio de dosis única, con dos secuencias, dos tratamientos y un período de lavado de 28 días. Las muestras de sangre se obtuvieron desde las 0 hasta las 96 horas después de la administración del medicamento. Los niveles plasmáticos de clonazepam se determinaron con un método validado por cromatografía líquida de alta eficiencia con detección ultravioleta (HPLC/UV, siglas en inglés. Los parámetros farmacocinéticos ABC0-96, ABC0-∞, Cmax, Tmax, t1/2, and ke se determinaron de los perfiles plasmáticos concentración-tiempo por el método no compartimental. El test de bioequivalencia se realizó con los datos transformados a logaritmo natural (ln de ABC0-∞and Cmax. Los intervalos de confianza del 90% para la relación producto de prueba/producto de referencia fueron de 87,9% a 103,6% y 84,4% a 104,0%, respectivamente. Estos resultados estuvieron dentro de los rangos de aceptación del 80,0% al 125%, establecidos por la FDA y se concluyó que ambos productos son bioequivalentes. In order to determine the bioequivalence of two formulations of clonazepam 2 mg tablets: Sedatril®/ Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia as a test product and Rivotril® (Roche Químicos e Farmacêuticas S. A., Rio de Janeiro, Brazil as a reference product, a bioavailability study was performed in 26 healthy volunteers. Test and reference products were administered under fasting conditions following a single dose, two-sequences, two treatments, crossover randomized

  5. 20 CFR 801.302 - Procedural rules.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Procedural rules. 801.302 Section 801.302... Action by the Board § 801.302 Procedural rules. Procedural rules for performance by the Board of its.... Such rules shall incorporate and implement the procedural requirements of section 21(b) of the...

  6. Static Correctness of Hierarchical Procedures

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff

    1990-01-01

    A system of hierarchical, fully recursive types in a truly imperative language allows program fragments written for small types to be reused for all larger types. To exploit this property to enable type-safe hierarchical procedures, it is necessary to impose a static requirement on procedure calls...

  7. 77 FR 23176 - Revisions to Procedural Rules

    Science.gov (United States)

    2012-04-18

    ... Procedural Rules AGENCY: Postal Regulatory Commission. ACTION: Advance notice of proposed rulemaking. SUMMARY... opinion conforms to the appropriate statutory requirements. 39 U.S.C. 3661(c). B. Current Procedural Regulations The Commission's procedural rules implementing the requirements of section 3661 can be found in 39...

  8. Report on COTECH test procedure and characterization techniques

    DEFF Research Database (Denmark)

    Islam, Mohammad Aminul

    .Characterization techniques and test procedure requirements for innovative self-ligating dental brackets (EO) Section 5.Characterization techniques and test procedure requirements for smart diagnostic chips comprising a microfluidic channel system (GBO) Section 6.Characterization techniques and test procedure...... requirements for multifunctional integrated lighting rear lamp for cars (CRP) Section 7.Characterization techniques and test procedure requirements for micro-fresnel lenses for cell phone flash lights (HEPTAGON) Section 8.Characterization techniques and test procedure requirements for 5 Pin Ric Connector...

  9. Determination of torasemide in human plasma and its bioequivalence study by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Lin Zhang

    2016-04-01

    Full Text Available A sensitive and selective method using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI–MS to determine the concentration of torasemide in human plasma samples was developed and validated. Tolbutamide was chosen as the internal standard (IS. The chromatography was performed on a Gl Sciences Inertsil ODS-3 column (100 mm×2.1 mm i.d., 5.0 µm within 5 min, using methanol with 10 mM ammonium formate (60:40, v/v as mobile phase at a flow rate of 0.2 mL/min. The targeted compound was detected in negative ionization at m/z 347.00 for torasemide and 269.00 for IS. The linearity range of this method was found to be within the concentration range of 1–2500 ng/mL (r=0.9984 for torasemide in human plasma. The accuracy of this measurement was between 94.05% and 103.86%. The extracted recovery efficiency was from 84.20% to 86.47% at three concentration levels. This method was also successfully applied in pharmacokinetics and bioequivalence studies in Chinese volunteers.

  10. Development and validation of an improved method for the quantitation of sertraline in human plasma using LC-MS-MS and its application to bioequivalence studies.

    Science.gov (United States)

    Zhang, Mengliang; Gao, Feng; Cui, Xiangyong; Zhang, Yunhui; Sun, Yantong; Gu, Jingkai

    2011-02-01

    A rapid and sensitive LC-MS-MS method for the quantitation of sertraline in human plasma was developed and validated. Sertraline and the internal standard, telmisartan, were cleaned up by protein precipitation from 100 μL of plasma sample, and analyzed on a TC-C18 column (5 μm, 150 × 4.6 mm i.d.) using 70% acetonitrile and 30% 10 mM ammonium acetate (0.1% formic acid) as mobile phase. The method was demonstrated to be linear from 0.1 ng/mL to 50 ng/mL with the lower limit of quantitation of 0.1 ng/mL. Intra- and inter-day precision were below 4.40% and 3.55%. Recoveries of sertraline at low, medium, and high levels were 88.0 ± 2.3%, 88.2 ± 1.9%, and 90.0 ± 2.0%, respectively. The method was successfully applied to a bioequivalence study of sertraline after a single oral administration of 50 mg sertraline hydrochloride tablets.

  11. Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by ultra high performance liquid chromatography tandem mass spectrometry and its application to a bioequivalence study.

    Science.gov (United States)

    Qiu, Xiangjun; Wang, Zhe; Wang, Bing; Zhan, Hui; Pan, Xiaofeng; Xu, Ren-ai

    2014-04-15

    An ultra high performance liquid chromatography tandem mass spectrometry (U-HPLC-MS/MS) method was developed and validated to determine irbesartan (IRB) and hydrochlorothiazide (HCTZ) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on an Acquity U-HPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the negative ion mode. The MRM transitions of m/z 427.2→206.9 and m/z 296.1→204.9 were used to quantify for IRB and HCTZ, respectively. The linearity of this method was found to be within the concentration range of 5-3000ng/mL for IRB, and 0.5-300ng/mL for HCTZ in human plasma, respectively. The lower limit of quantification (LLOQ) was 5ng/mL and 0.5ng/mL for IRB and HCTZ in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 12% for both IRB and HCTZ. The analysis time of per sample was 2.5min. The developed and validated method was successfully applied to a bioequivalence study of IRB (300mg) with HCTZ (12.5mg) tablet in Chinese healthy volunteers (N=20). Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Crown lengthening procedures

    Directory of Open Access Journals (Sweden)

    AA. Khoshkhonejad

    1994-06-01

    Full Text Available Nowadays, due to recent developments and researches in dental science, it is possible to preserve and restore previously extracted cases such as teeth with extensive caries, fractured or less appropriate cases for crown coverage as well as teeth with external perforation caused by restorative pins. In order to restore the teeth with preservation of periodontium, we should know thoroughly physiological aspects of periodontium and protection of Biologic Width which is formed by epithelial and supracrestal connective tissue connections. Considering biologic width is one of the principal rules of teeth restoration, otherwise we may destruct periodontal tissues. Several factors are involved in placing a restoration and one of the most important ones is where the restoration margin is terminated. Many studies have been conducted on the possible effects of restoration margin on the gingiva and due to the results of these studies it was concluded that restoration margin should be finished supragingivally. However, when we have to end the restoration under Gingival Crest, First a healthy gingival sulcus is required. Also, we should not invade the biological width. Since a normal biologic with is reported 2 mm and sound tooth tissue should be placed at least 2 mm coronal to the epithelial tissue, the distance between sound tooth tissue and crown margin should be at least 4mm. Thus, performing crown lengthening is essential to increase the clinical crown length. Basically, two objectives are considered: 1 restorative 2 esthetic (gummy smile Surgical procedure includes gingivectomy and flap procedure. Orthodontic procedure involves orthodontic extrusion or force eruption technique which is controlled vertical movements of teeth into occlusion. Besides, this procedure can also used to extrude teeth defects from the gingival tissue. By crown lengthening, tooth extraction is not required and furthermore, adjacent teeth preparation for placing a fixed

  13. PACS policies and procedures.

    Science.gov (United States)

    Knepper, Daniel

    2007-01-01

    Documentation of policies and procedures are critical for the proper operation and management of a picture archival and communication system (PACS). Policies, procedures, and site specific documentation may be organized in several categories. Through the use of broad categories one can easily begin to break down the specific areas which require attention and prioritize them as necessary. One way to categorize them is: administration, maintenance, support, architecture and integration, and disaster recovery/business continuity. One area that requires a great deal of focus and discipline is a policy for "change management." It is essential to have a policy in place for making changes to the information system. This would include not only changes to the system such as software upgrades, but changes to workflows such as how images are being distributed, compression settings, network settings, monitor settings, locations of workstations, integration, and disaster recovery/ business continuity. Modifying existing information technology (IT) policies and using published resources can largely simplify the development of organization specific policies and procedures.

  14. Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2017-07-01

    Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

  15. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

    Science.gov (United States)

    Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

    2009-10-01

    Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

  16. Clinical utility of topiramate extended-release capsules (USL255): Bioequivalence of USL255 sprinkled and intact capsule in healthy adults and an in vitro evaluation of sprinkle delivery via enteral feeding tubes.

    Science.gov (United States)

    Clark, Annie M; Pellock, John M; Holmay, Mary; Anders, Bob; Cloyd, James

    2016-04-01

    The objectives of these two studies were to determine if beads from extended-release topiramate capsules sprinkled onto soft food are bioequivalent to the intact capsule and if beads from the capsule can be passed through enteral gastrostomy (G-) and jejunostomy (J-) feeding tubes. Bioequivalence of 200-mg USL255 (Qudexy XR [topiramate] extended-release capsules) sprinkled onto soft food (applesauce) versus the intact capsule was evaluated in a phase 1, randomized, single-dose, crossover study (N=36). Pharmacokinetic evaluations included area under the curve (AUC), maximum plasma concentration (Cmax), time to Cmax (Tmax), and terminal elimination half-life (t1/2). If 90% confidence intervals (CI) of the ratio of geometric least-squares means were between 0.80 and 1.25, AUC and Cmax were considered bioequivalent. In separate in vitro experiments, 100-mg USL255 beads were passed through feeding tubes using gentle syringe pressure to develop a clog-free bead-delivery method. Multiple tube sizes (14- to 18-French [Fr] tubes), dilutions (5 mg/15 mL-25 mg/15 mL), and diluents (deionized water, apple juice, Ketocal, sparkling water) were tested. Area under the curve and Cmax for USL255 beads sprinkled onto applesauce were bioequivalent to the intact capsule (GLSM [90% CI]: AUC0-t 1.01 [0.97-1.04], AUC0-∞ 1.02 [0.98-1.05]; Cmax 1.09 [1.03-1.14]). Median Tmax was 4h earlier for USL255 sprinkled versus the intact capsule (10 vs 14 h; p=0.0018), and t1/2 was similar (84 vs 82 h, respectively). In 14-Fr G-tubes, USL255 beads diluted in Ketocal minimized bead clogging versus deionized water. Recovery of USL255 beads diluted in deionized water was nearly 100% in 16-Fr G-, 18-Fr G-, and 18-Fr J-tubes. For patients with difficulty swallowing pills, USL255 sprinkled onto applesauce offers a useful once-daily option for taking topiramate. USL255 beads were also successfully delivered in vitro through ≥14-Fr G- or J-tubes, with tube clogging minimized by portioning the dose and

  17. Bioequivalence of two metformin formulations: 850 mg tablets in healthy colombian volunteers Bioequivalencia de dos formulaciones de metformina, tabletas de 850 mg, en voluntarios sanos colombianos

    Directory of Open Access Journals (Sweden)

    Ómar de Jesús Correa Cano

    2005-03-01

    Full Text Available Introduction: Metformin is an orally active antidiabetic agent used to treat type II diabetes; it is found in the Colombian market in both the innovator brand and the generic formulations. The latter have to prove some biopharmaceutical quality outcomes to guarantee interchangeable proprieties. Objective: To determine whether the drug Dimefor®/Metformina MK is bioequivalent to the reference product Glucophage®, when the products are administrated, at the same dose, to a group of healthy volunteers. Method: The study was made with 24 healthy volunteers who met the inclusion criteria and spontaneously decided to participate after being thoroughly informed. We used a two-sequence threeperiod randomized, crossed and double-blind study. The volunteers took an 850 mg dose of each medicine; then, blood samples were taken throughout 24 hours and the metformin quantification in plasma was determined by High Performance Liquid Chromatography with UV detection (HPLC/UV. For statistical analysis, Schuirmann’s test was used. Results: The study showed that both preparations are bioequivalent; confidence intervals for ln AUC0-∞, ln Cmax, ln AUC0-Tmax and Tmax were [84.6-100.0%], [89.1-109.0%], [83.4–01.4%] and [85.1-109.8% ], respectively. Introducción: la metformina es un antihiperglicemiante útil en el manejo de la diabetes mellitus tipo II, del que se encuentran en el mercado colombiano tanto el producto innovador como diferentes formulaciones genéricas. Para garantizar la seguridad y eficacia de estas últimas, es necesario demostrar su bioequivalencia con respecto al producto innovador. Objetivo: determinar si el producto Dimefor®/Metformina MK es bioequivalente con el producto Glucophage® (referencia cuando se administran en dosis iguales a un grupo de voluntarios sanos. Método: el estudio se realizó sobre veinticuatro voluntarios que cumplieron con los requisitos de inclusión y decidieron participar espontáneamente después de ser

  18. Application of a rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of bumetanide in human plasma for a bioequivalence study.

    Science.gov (United States)

    Patel, Dinesh S; Sharma, Naveen; Patel, Mukesh C; Patel, Bhavin N; Shrivastav, Pranav S; Sanyal, Mallika

    2012-07-01

    A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of bumetanide in human plasma using tamsulosin as internal standard (IS). The analyte and IS were extracted from 200 μL of human plasma via solid phase extraction and the chromatographic separation was achieved on Peerless Basic C18 (100 mm × 4.6 mm, 3 μm) column under isocratic conditions. Detection of bumetanide and IS was done by tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for bumetanide and IS were m/z 365.2→240.2 and 409.2→228.2 respectively. The method was fully validated as per the US FDA guidelines. The limit of detection and lower limit of quantitation of the method were 0.03 and 0.30 ng/mL respectively with a linear dynamic range of 0.30-200.0 ng/mL for bumetanide. The intra-batch and inter-batch precision (% CV) was ≤6.9% while the mean extraction recovery was >90% across quality control levels. The method is selective in presence of four diuretic drugs and some commonly used medications by healthy volunteers. It was successfully applied to a bioequivalence study of 2mg bumetanide tablet formulation in 10 healthy Indian male subjects under fasting condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 42 incurred samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women

    Directory of Open Access Journals (Sweden)

    Pravin G. Vanol

    2016-08-01

    Full Text Available A rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm column using methanol-0.1% formic acid in water (85:15, v/v as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10–100 ng/mL (r2≥0.9990 using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR of 74 subject samples.

  20. A simple and sensitive HPLC method for analysis of imipramine in human plasma with UV detection and liquid-liquid extraction: Application in bioequivalence studies.

    Science.gov (United States)

    Rezazadeh, Mahboubeh; Emami, Jaber

    2016-01-01

    High-performance liquid chromatography (HPLC) methods employing ultraviolet (UV) detector are not sufficiently sensitive to measure the low plasma concentrations following single oral dose of imipramine. Therefore, in the present study a simple, rapid and yet sensitive HPLC method with UV detection was developed and validated for quantitation of imipramine in human plasma samples. An efficient liquid-liquid extraction (LLE) of imipramine from plasma with the mixture of hexane/isoamyl alcohol (98:2) and back extraction of the drug in acidic medium concomitant with evaporation of organic phase allowed the use of UV detector to conveniently measure plasma levels of this compound as low level as 3 ng/ml. Separation was achieved on a μ-Bondapak C18 HPLC column using sodium hydrogen phosphate solution (0.01 M)/acetonitrile (60/40 v/v) at pH 3.5 ± 0.1 at 1.5 ml/min. Trimipramine was used as the internal standard for analysis of plasma samples. The retention times for imipramine and trimipramine were 4.3 and 5.2 min, respectively. Calibration curve was linear in the range of 3-40 ng/ml using human plasma with the average extraction recovery of 85 ± 5%. Imipramine was found to be stable in plasma samples with no evidence of degradation during three freeze-thaw cycles and three months storage at -70°C. The current validated method was finally applied in bioequivalence studies of two different imipramine products according to a standard two-way crossover design with a two weeks washout period.

  1. Application of an LC–MS/MS method for the analysis of amlodipine, valsartan and hydrochlorothiazide in polypill for a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Jaivik V. Shah

    2017-10-01

    Full Text Available A sensitive and selective method has been proposed for the simultaneous determination of amlodipine (AML, valsartan (VAL and hydrochlorothiazide (HCTZ in human plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analytes and their deuterated analogs were quantitatively extracted from 100 µL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18e (100 mm × 4.6 mm analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively, under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/mL for AML, 5.00–10,000 ng/mL for VAL and 0.20–200 ng/mL for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision (% CV across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation (test and reference in 18 healthy Indian males under fasting. The mean log-transformed ratios of Cmax, AUC0–120h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.

  2. 78 FR 21517 - Practices and Procedures

    Science.gov (United States)

    2013-04-11

    ... Administrative Procedure Act (APA). However, an exemption from notice and comment rulemaking requirements exists... the use of APA notice and comment procedures impracticable. The ``unnecessary'' prong of the agency's... this amendment from the normal APA notice-and-comment procedures. The public interest prong of the good...

  3. Specified assurance level sampling procedure

    International Nuclear Information System (INIS)

    Willner, O.

    1980-11-01

    In the nuclear industry design specifications for certain quality characteristics require that the final product be inspected by a sampling plan which can demonstrate product conformance to stated assurance levels. The Specified Assurance Level (SAL) Sampling Procedure has been developed to permit the direct selection of attribute sampling plans which can meet commonly used assurance levels. The SAL procedure contains sampling plans which yield the minimum sample size at stated assurance levels. The SAL procedure also provides sampling plans with acceptance numbers ranging from 0 to 10, thus, making available to the user a wide choice of plans all designed to comply with a stated assurance level

  4. The importance of procedural defects in Atomic Law

    International Nuclear Information System (INIS)

    Ossenbuehl, F.

    1981-01-01

    The Muelheim-Kaerlich decision of the Federal Constitutional Court has brought about a 'revaluation' of procedural requirements. This has caused some insecurity in the application of procedural requirements, e.g. whether a license under Nuclear Law, granted without public participation in spite of procedural requirements, can be revolved on the basis of this procedural defect alone. The answer depends on the applicability of Sect. 46 VwVfG (Act on Procedural Rules) in Nuclear Law. (orig.) [de

  5. A review on drug approval process in US, Europe and India-dossier, bioavailability and bioequivalence studies

    OpenAIRE

    Madagoni, krishna; Saidireddy, Uppunuri; ., Himaja

    2017-01-01

    Pharmaceutical Regulatory Affairs (PRA) is a vital unit in a pharmaceutical company that successfully drives the Research and Development (R&D) efforts of the company to the market. In the present scenario, countries have different regulatory requirements for approval of a new drug. The single regulatory approach for marketing authorization application (MAA) of a new drug product applicable to various countries (on the basis of single dossier) is utmost difficult. Therefore, the knowledge of ...

  6. Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

    Science.gov (United States)

    Stavchansky, Salomon

    2008-06-01

    Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

  7. 19 CFR 143.44 - RLF procedure.

    Science.gov (United States)

    2010-04-01

    ... electronically, using EIP, any invoice data required by CBP. (b) Electronic transmission of payment. For RLF... free will be accepted by CBP. If electronic invoice or additional electronic documentation is required... (CONTINUED) SPECIAL ENTRY PROCEDURES Remote Location Filing § 143.44 RLF procedure. (a) Electronic...

  8. 48 CFR 6302.12 - Regular procedure (Rule 12).

    Science.gov (United States)

    2010-10-01

    ... CONTRACT APPEALS RULES OF PROCEDURE 6302.12 Regular procedure (Rule 12). Under the regular procedure the parties are required to file pleadings with the Board (Rule 13). The regular procedure affords the parties... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Regular procedure (Rule 12...

  9. A practical CBA-based screening procedure for identification of river basins where the costs of fulfilling the WFD requirements may be disproportionate – applied to the case of Denmark

    DEFF Research Database (Denmark)

    Jensen, Carsten Lynge; Jacobsen, Brian H.; Olsen, Søren Bøye

    2013-01-01

    procedure to a total of 23 river basin areas in Denmark where costs and benefits are estimated for each of the areas. The results suggest that costs could be disproportionate in several Danish river basins. The sensitivity analysis further helps to pinpoint two or three basins where we suggest that much......The European Union’s (EU) Water Framework Directive (WFD) is implemented as an instrument to obtain good ecological status in waterbodies of Europe. The directive recognises the need to accommodate social and economic considerations to obtain cost-effective implementation of the directive...... disproportionate costs at the national level. Specifically, we propose to use a screening procedure based on a relatively conservative cost–benefit analysis (CBA) as a first step towards identifying areas where costs could be disproportionate. We provide an empirical example by applying the proposed screening...

  10. Procedures: Source Term Measurement Program

    International Nuclear Information System (INIS)

    Dyer, N.C.; Keller, J.H.; Nieschmidt, E.B.; Motes, B.J.

    1977-10-01

    The report contains procedures for the Source Term Measurement Project being performed by Idaho National Engineering Laboratory for the Nuclear Regulatory Commission. This work is being conducted for the Office of Nuclear Regulatory Research in support of requirements of the Effluent Treatment Systems Branch of the Office of Nuclear Reactor Regulation. This project is designed to obtain source term information at operating light water reactors to update the parameters used in NRC calculational models (GALE codes). Detailed procedures and methods used for collection and analysis of samples are presented. This provides a reference base to supplement a series of reports to be issued by the Source Term Measurements Project which will present data obtained from measurements in specific nuclear power stations. Reference to appropriate parts of these procedures will be made as required

  11. MITG test procedure and results

    International Nuclear Information System (INIS)

    Eck, M.E.; Mukunda, M.

    1983-01-01

    Elements and modules for Radioisotope Thermoelectric Generator have been performance tested since the inception of the RTG program. These test articles seldom resembled flight hardware and often lacked adequate diagnostic instrumentation. Because of this, performance problems were not identified in the early stage of program development. The lack of test data in an unexpected area often hampered the development of a problem solution. A procedure for conducting the MITG Test was developed in an effort to obtain data in a systematic, unambiguous manner. This procedure required the development of extensive data acquisition software and test automation. The development of a facility to implement the test procedure, the facility hardware and software requirements, and the results of the MITG testing are the subject of this paper

  12. PC based temporary shielding administrative procedure (TSAP)

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, D.E.; Pederson, G.E. [Sargent & Lundy, Chicago, IL (United States); Hamby, P.N. [Commonwealth Edison Co., Downers Grove, IL (United States)

    1995-03-01

    A completely new Administrative Procedure for temporary shielding was developed for use at Commonwealth Edison`s six nuclear stations. This procedure promotes the use of shielding, and addresses industry requirements for the use and control of temporary shielding. The importance of an effective procedure has increased since more temporary shielding is being used as ALARA goals become more ambitious. To help implement the administrative procedure, a personal computer software program was written to incorporate the procedural requirements. This software incorporates the useability of a Windows graphical user interface with extensive help and database features. This combination of a comprehensive administrative procedure and user friendly software promotes the effective use and management of temporary shielding while ensuring that industry requirements are met.

  13. PC based temporary shielding administrative procedure (TSAP)

    International Nuclear Information System (INIS)

    Olsen, D.E.; Pederson, G.E.; Hamby, P.N.

    1995-01-01

    A completely new Administrative Procedure for temporary shielding was developed for use at Commonwealth Edison's six nuclear stations. This procedure promotes the use of shielding, and addresses industry requirements for the use and control of temporary shielding. The importance of an effective procedure has increased since more temporary shielding is being used as ALARA goals become more ambitious. To help implement the administrative procedure, a personal computer software program was written to incorporate the procedural requirements. This software incorporates the useability of a Windows graphical user interface with extensive help and database features. This combination of a comprehensive administrative procedure and user friendly software promotes the effective use and management of temporary shielding while ensuring that industry requirements are met

  14. Regulations and Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Young, Lydia J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-07-25

    The purpose of the Regulations and Procedures Manual (RPM) is to provide LBNL personnel with a reference to University and Lawrence Berkeley National Laboratory (LBNL or Laboratory) policies and regulations by outlining normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory organizations. Much of the information in this manual has been condensed from detail provided in LBNL procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. RPM sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the LBNL organization responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which organization is responsible for a policy, please contact Requirements Manager Lydia Young or the RPM Editor.

  15. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    -way chemometrical methods, such as PCA and PARAFAC models for analysing spatial and depth profiles of sea water samples, defined by three data modes: depth, variables and geographical location. Emphasis was also put on predicting fluorescence values, as being a natural measure of biological activity, by applying...... if contamination in the data is present. For this becoming a standard procedure, further work is required, aiming at implementing reliable robust algorithms into standard statistical programs.......The general aim of the thesis was to contribute to the improvement of data analytical techniques within the chemometric field. Regardless the multivariate structure of the data, it is still common in some fields to perform uni-variate data analysis using only simple statistics such as sample mean...

  16. Radiological Work Planning and Procedures

    CERN Document Server

    Kurtz, J E

    2000-01-01

    Each facility is tasked with maintaining personnel radiation exposure as low as reasonably achievable (ALARA). A continued effort is required to meet this goal by developing and implementing improvements to technical work documents (TWDs) and work performance. A review of selected TWDs from most facilities shows there is a need to incorporate more radiological control requirements into the TWD. The Radioactive Work Permit (RWP) provides a mechanism to place some of the requirements but does not provide all the information needed by the worker as he/she is accomplishing the steps of the TWD. Requiring the engineers, planners and procedure writers to put the radiological control requirements in the work steps would be very easy if all personnel had a strong background in radiological work planning and radiological controls. Unfortunately, many of these personnel do not have the background necessary to include these requirements without assistance by the Radiological Control organization at each facility. In add...

  17. Grant Management Handbook: A Procedures Manual to Uniform Grants and Contract Management Standards Based on Texas Civil Statutes, Article 4413 (32g) and the Common Rule for Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments.

    Science.gov (United States)

    Conable, Sharon R.

    This manual provides a conceptual framework and reference source concerning the reporting, financial contractual, and auditing requirements for recipients of Texas State Library grants funded with state and federal funds under the Library Systems Act (LSA) and the Library Services and Construction Act (LSCA). The handbook is divided into 12…

  18. Bioequivalence of two levothyroxine tablet formulations without and with mathematical adjustment for basal thyroxine levels in healthy Argentinian volunteers: a single-dose, randomized, open-label, crossover study.

    Science.gov (United States)

    Di Girolamo, Guillermo; Keller, Guillermo A; de Los Santos, Antonio R; Schere, Daniel; Gonzalez, Claudio D

    2008-11-01

    Levothyroxine has a narrow therapeutic index; therefore, precise and accurate assessment of the bioequivalence of different levothyroxine products is critical. Bioavailability estimates of levothyroxine formulations might be affected by baseline concentrations of the hormone. The aim of this study was to assess the bioequivalence of 100 microg of a test (T4 Montpellier 100, Química Montpellier S.A., Buenos Aires, Argentina) and reference (Synthroid, Abbott Laboratories, Abbott Park, Illinois) formulation of levothyroxine. We also compared 2 methods of levothyroxine measurements: without and with baseline correction for endogenous levothyroxine. This randomized, open-label, 2-sequence, crossover study with a 65-day washout period was carried out in healthy, white, euthyroid volunteers following a single dose of sodium levothyroxine 600 microg. Blood samples were collected at 30 and 15 minutes prior to administration, and 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 hours to determine thyroxine; serum thyrotropin (TSH) concentrations were determined 30 minutes before administration and 48 hours after administration. Serum concentrations of thyroxine were determined through radioimmunoassay and serum TSH concentrations were determined by a validated 2-site immunoradiometric assay. The formulations are considered to be equivalent if the 90% CI ratios for C(max) and AUC(0-last) are within 80% to 125%, per the US Food and Drug Administration (FDA). Adverse event monitoring was performed throughout the study by assessing clinical parameters (eg, blood pressure, electrocardiogram) and patient reports. A total of 24 volunteers (16 male, 8 female; mean [SD] age, 30.2 [4.6] years [range, 21-40 years]; mean [SD] weight, 71.71 [7.52] kg [range, 58-83 kg]) were included in the study. Without adjustment for baseline levels of endogenous levothyroxine, geometric mean C(max) for the test and reference formulations were 8.92 and 9.39 microg/dL, respectively

  19. Indicators of Evidence for Bioequivalence

    Directory of Open Access Journals (Sweden)

    Stephan Morgenthaler

    2016-08-01

    Full Text Available Some equivalence tests are based on two one-sided tests, where in many applications the test statistics are approximately normal. We define and find evidence for equivalence in Z-tests and then one- and two-sample binomial tests as well as for t-tests. Multivariate equivalence tests are typically based on statistics with non-central chi-squared or non-central F distributions in which the non-centrality parameter λ is a measure of heterogeneity of several groups. Classical tests of the null λ ≥ λ 0 versus the equivalence alternative λ < λ 0 are available, but simple formulae for power functions are not. In these tests, the equivalence limit λ 0 is typically chosen by context. We provide extensions of classical variance stabilizing transformations for the non-central chi-squared and F distributions that are easy to implement and which lead to indicators of evidence for equivalence. Approximate power functions are also obtained via simple expressions for the expected evidence in these equivalence tests.

  20. Design Procedure for Hybrid Ventilation

    DEFF Research Database (Denmark)

    Heiselberg, Per; Tjelflaat, Per Olaf

    Mechanical and natural ventilation systems have developed separately during many years. The natural next step in this development is development of ventilation concepts that utilises and combines the best features from each system into a new type of ventilation system - Hybrid Ventilation....... Buildings with hybrid ventilation often include other sustainable technologies and an energy optimisation requires an integrated approach in the design of the building and its mechanical systems. Therefore, the hybrid ventilation design procedure differs from the design procedure for conventional HVAC....... The first ideas on a design procedure for hybrid ventilation is presented and the different types of design methods, that is needed in different phases of the design process, is discussed....

  1. Seamless Requirements

    OpenAIRE

    Naumchev, Alexandr; Meyer, Bertrand

    2017-01-01

    Popular notations for functional requirements specifications frequently ignore developers' needs, target specific development models, or require translation of requirements into tests for verification; the results can give out-of-sync or downright incompatible artifacts. Seamless Requirements, a new approach to specifying functional requirements, contributes to developers' understanding of requirements and to software quality regardless of the process, while the process itself becomes lighter...

  2. Acceptance test procedure for Project W-280

    International Nuclear Information System (INIS)

    Stites, C.G.

    1994-01-01

    This Document is the Acceptance Test Procedure for 200 Area C and SY Tank Farm Lighting Upgrade. This Acceptance Test Procedure has been prepared to demonstrate that the Tank Farm Lighting Systems function correctly as required by project criteria and as intended by design

  3. 22 CFR 62.5 - Application procedure.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Application procedure. 62.5 Section 62.5 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM General Provisions § 62.5 Application procedure. (a) Any entity meeting the eligibility requirements set forth in...

  4. W-087 Acceptance test procedure. Revision 1

    International Nuclear Information System (INIS)

    Joshi, A.W.

    1997-01-01

    This Acceptance Test Procedure/Operational Test Procedure (ATP/OTP) has been prepared to demonstrate that the Electrical/Instrumentation and Mechanical systems function as required by project criteria and to verify proper operation of the integrated system including the interlocks

  5. 40 CFR 7.90 - Grievance procedures.

    Science.gov (United States)

    2010-07-01

    ...) Exception. Recipients with fewer than fifteen (15) full-time employees need not comply with this section... Recipients § 7.90 Grievance procedures. (a) Requirements. Each recipient shall adopt grievance procedures... significantly impair the recipient's ability to provide benefits or services. ...

  6. Anesthetic considerations for interventional pulmonary procedures.

    Science.gov (United States)

    Pawlowski, John

    2013-02-01

    To discuss the anesthetic considerations of various procedures now performed by the interventional pulmonologist. With recent technological advances, many of these procedures represent acceptable alternatives to the invasive surgical procedures. For example, the placement of endobronchial valves can substitute for lung reduction surgery and can greatly reduce the postoperative recovery period. However, many of these complex procedures require anesthesia services. The nature and indication for the procedure as well as the patient's overall health will have an impact on the anesthetic choice. New studies have documented common complications from interventional pulmonology procedures and recent ways to avoid these complications have been suggested. Strategies to avoid obstruction, bleeding, pneumothorax and air embolism are discussed in this article. Potential benefits of high frequency jet ventilation in reducing airway pressures and, perhaps, barotraumas are cited. Novel interventional pulmonary procedures are described. As the array of diagnostic and therapeutic pulmonary interventions is expanding, the types of anesthetic techniques and ventilatory modes are varying to fit the procedural requirements. Some pulmonary procedures are best accomplished in the lightly sedated patient, who is breathing spontaneously, whereas procedures that use the working channel of a rigid bronchoscope are better performed in the patient under general anesthesia and mechanical ventilation that often use jet ventilation to minimize respiratory movements.

  7. MITS Data Acquisition Subsystem Acceptance Test procedure

    International Nuclear Information System (INIS)

    Allison, R.

    1980-01-01

    This is an acceptance procedure for the Data Acquisition Subsystem of the Machine Interface Test System (MITS). Prerequisites, requirements, and detailed step-by-step instruction are presented for inspecting and performance testing the subsystem

  8. Small Optics Laser Damage Test Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, Justin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-10-19

    This specification defines the requirements and procedure for laser damage testing of coatings and bare surfaces designated for small optics in the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL).

  9. The procedural egalitarian solution

    NARCIS (Netherlands)

    Dietzenbacher, Bas; Borm, Peter; Hendrickx, Ruud

    2017-01-01

    In this paper we introduce and analyze the procedural egalitarian solution for transferable utility games. This new concept is based on the result of a coalitional bargaining procedure in which egalitarian considerations play a central role. The procedural egalitarian solution is the first

  10. The Procedural Egalitarian Solution

    NARCIS (Netherlands)

    Dietzenbacher, Bas; Borm, Peter; Hendrickx, Ruud

    2016-01-01

    In this paper we introduce and analyze the procedural egalitarian solution for transferable utility games. This new concept is based on the result of a coalitional bargaining procedure in which egalitarian considerations play a central role. The procedural egalitarian solution is the first

  11. Program Baseline Change Control Procedure

    International Nuclear Information System (INIS)

    1993-02-01

    This procedure establishes the responsibilities and process for approving initial issues of and changes to the technical, cost, and schedule baselines, and selected management documents developed by the Office of Civilian Radioactive Waste Management (OCRWM) for the Civilian Radioactive Waste Management System. This procedure implements the OCRWM Baseline Management Plan and DOE Order 4700.1, Chg 1. It streamlines the change control process to enhance integration, accountability, and traceability of Level 0 and Level I decisions through standardized Baseline Change Proposal (BCP) forms to be used by the Level 0, 1, 2, and 3 Baseline Change Control Boards (BCCBs) and to be tracked in the OCRWM-wide Configuration Information System (CIS) Database.This procedure applies to all technical, cost, and schedule baselines controlled by the Energy System Acquisition Advisory Board (ESAAB) BCCB (Level 0) and, OCRWM Program Baseline Control Board (PBCCB) (Level 1). All baseline BCPs initiated by Level 2 or lower BCCBs, which require approval from ESAAB or PBCCB, shall be processed in accordance with this procedure. This procedure also applies to all Program-level management documents controlled by the OCRWM PBCCB

  12. Designing Flightdeck Procedures: Literature Resources

    Science.gov (United States)

    Feldman, Jolene; Barshi, Immanuel; Degani, Asaf; Loukopoulou, Loukia; Mauro, Robert

    2017-01-01

    This technical publication contains the titles, abstracts, summaries, descriptions, and/or annotations of available literature sources on procedure design and development, requirements, and guidance. It is designed to provide users with an easy access to available resources on the topic of procedure design, and with a sense of the contents of these sources. This repository of information is organized into the following publication sources: Research (e.g., journal articles, conference proceedings), Manufacturers' (e.g., operation manuals, newsletters), and Regulatory and/or Government (e.g., advisory circulars, reports). An additional section contains synopses of Accident/Incident Reports involving procedures. This work directly supports a comprehensive memorandum by Barshi, Mauro, Degani, & Loukopoulou (2016) that summarizes the results of a multi-year project, partially funded by the FAA, to develop technical reference materials that support guidance on the process of developing cockpit procedures (see "Designing Flightdeck Procedures" https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20160013263.pdf). An extensive treatment of this topic is presented in a forthcoming book by the same authors.

  13. Procedure generation and verification

    International Nuclear Information System (INIS)

    Sheely, W.F.

    1986-01-01

    The Department of Energy has used Artificial Intelligence of ''AI'' concepts to develop two powerful new computer-based techniques to enhance safety in nuclear applications. The Procedure Generation System, and the Procedure Verification System, can be adapted to other commercial applications, such as a manufacturing plant. The Procedure Generation System can create a procedure to deal with the off-normal condition. The operator can then take correct actions on the system in minimal time. The Verification System evaluates the logic of the Procedure Generator's conclusions. This evaluation uses logic techniques totally independent of the Procedure Generator. The rapid, accurate generation and verification of corrective procedures can greatly reduce the human error, possible in a complex (stressful/high stress) situation

  14. Meeting US and European supplier control requirements.

    Science.gov (United States)

    Donawa, Maria

    2009-01-01

    Medical device manufacturers operating under European quality system requirements are sometimes surprised to learn that their supplier control procedures do not fully meet United States (US) requirements. This article discusses important differences between US and European requirements for controlling suppliers.

  15. INITIATION AND CONDUCT OF ADMINISTRATIVE PROCEDURE

    Directory of Open Access Journals (Sweden)

    Milan Stipic

    2013-12-01

    Full Text Available General administrative procedure act contains legal norms that are valid for all identical cases. In addition to the general, there are special administrative procedures, customized to the specific administrative areas. Procedure initiation is regulated. Administrative procedure can be initiated at the request of the proponent and ex officio. When the official determines that the conditions for the conduct of administrative procedure are met, before making a decision, all the facts and circumstances relevant to the resolution of administrative matter have to be identified. When there are no legal requirements for the initiation of procedures, the official shall make a decision to reject the application of the party. The procedure is initiated ex officio when stipulated by law or when protection of public interest requires it. When initiating procedure ex officio, the public authority shall take into consideration the petition or other information that indicate the need to protect the public interest. In such cases the applicant is not a party, and the official is obliged to notify the applicant, if initiation of procedures is not accepted ex officio. Based on the notification, the applicant has a right to complain, including the situation when there is no response within the prescribed period of 30 days. Public authority may, therefore it is not obliged to, initiate administrative procedure by public announcement only in a situation where the parties are unknown, while it is obliged to initiate procedure by public announcement when this method of initiating the procedure is prescribed by law. Initiation of procedure with public announcement occurs in rare cases. Due to the application of efficiency and cost-effectiveness principle, two or more administrative procedures can be merged into one procedure by a conclusion. The condition for this is that the rights or obligations of the parties are based on the same legal basis and on the same or

  16. Operating manual for the High Flux Isotope Reactor: operating procedures

    Energy Technology Data Exchange (ETDEWEB)

    1982-11-01

    Procedures are presented for reactor operation; instrumentation and control; reactor components; research facilities; cooling systems; containment heating, venting, and air conditioning; emergency procedures; waste systems; on-site utilities; records and data accumulation; auxiliary equipment; and technical specification requirements.

  17. MR-Guided Interventional Procedures: A Review

    International Nuclear Information System (INIS)

    Blanco Sequeiros, R.; Ojala, R.; Kariniemi, J.; Peraelae, J.; Niinimaeki, J.; Reinikainen, H.; Tervonen, O.

    2005-01-01

    Magnetic resonance imaging (MRI) has emerged as a potential guidance tool for a variety of procedures. Diagnostic and therapeutic procedures using either open surgical or percutaneous access are performed. They span from simple lesion targeting and biopsy to complex applications requiring multiple tasks performed simultaneously or in rapid succession. These tasks include instrument guidance and therapy monitoring as well as procedural follow-up. The interventional use of MRI (IMRI) is increasing steadily. This article reviews the prerequisites, systems, and clinical interventional procedures of IMRI

  18. Automated emergency operating procedures

    International Nuclear Information System (INIS)

    Perez-Ramirez, G.; Nelson, P.F.

    1990-01-01

    This paper describes the development of a training tool for the symptom oriented emergency operating procedures used at the Laguna Verde Nuclear Power Plant. EOPs and operator training are intended to assist the operator for managing accident situations. A prototype expert system based on the EOPs has been developed for operator training. The demonstration expert system was developed using a commercial shell. The knowledge base consists of two parts. The specific operator actions to be executed for 5 selected accident sequences and the EOPs steps for the reactor pressure vessel control of the water level, pressure, and power. The knowledge is expressed in the form of IF-THEN production rules. A typical training session will display a set of conditions and will prompt the trainee to indicate the appropriate step to perform. This mode will guide the trainee through selected accident sequences. A second mode of the expert system will prompt the trainee for the current plant conditions and the expert system will respond with the EOPs which are required to be performed under these conditions. This allows the trainee to study What if situations

  19. Deterministic effects of interventional radiology procedures

    International Nuclear Information System (INIS)

    Shope, Thomas B.

    1997-01-01

    The purpose of this paper is to describe deterministic radiation injuries reported to the Food and Drug Administration (FDA) that resulted from therapeutic, interventional procedures performed under fluoroscopic guidance, and to investigate the procedure or equipment-related factors that may have contributed to the injury. Reports submitted to the FDA under both mandatory and voluntary reporting requirements which described radiation-induced skin injuries from fluoroscopy were investigated. Serious skin injuries, including moist desquamation and tissues necrosis, have occurred since 1992. These injuries have resulted from a variety of interventional procedures which have required extended periods of fluoroscopy compared to typical diagnostic procedures. Facilities conducting therapeutic interventional procedures need to be aware of the potential for patient radiation injury and take appropriate steps to limit the potential for injury. (author)

  20. Pollutant Assessments Group Procedures Manual: Volume 1, Administrative and support procedures

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    This manual describes procedures currently in use by the Pollutant Assessments Group. The manual is divided into two volumes: Volume 1 includes administrative and support procedures, and Volume 2 includes technical procedures. These procedures are revised in an ongoing process to incorporate new developments in hazardous waste assessment technology and changes in administrative policy. Format inconsistencies will be corrected in subsequent revisions of individual procedures. The purpose of the Pollutant Assessments Groups Procedures Manual is to provide a standardized set of procedures documenting in an auditable manner the activities performed by the Pollutant Assessments Group (PAG) of the Health and Safety Research Division (HASRD) of the Environmental Measurements and Applications Section (EMAS) at Oak Ridge National Laboratory (ORNL). The Procedures Manual ensures that the organizational, administrative, and technical activities of PAG conform properly to protocol outlined by funding organizations. This manual also ensures that the techniques and procedures used by PAG and other contractor personnel meet the requirements of applicable governmental, scientific, and industrial standards. The Procedures Manual is sufficiently comprehensive for use by PAG and contractor personnel in the planning, performance, and reporting of project activities and measurements. The Procedures Manual provides procedures for conducting field measurements and includes program planning, equipment operation, and quality assurance elements. Successive revisions of this manual will be archived in the PAG Document Control Department to facilitate tracking of the development of specific procedures.

  1. Civil Procedure In Denmark

    DEFF Research Database (Denmark)

    Werlauff, Erik

    The book contains an up-to-date survey of Danish civil procedure after the profound Danish procedural reforms in 2007. It deals with questions concerning competence and function of Danish courts, commencement and preparation of civil cases, questions of evidence and burden of proof, international...... procedural questions, including relations to the Brussels I Regulation and Denmark's participation in this Regulation via a parallel convention with the EU countries, impact on Danish civil procedure of the convention on human rights, preparation and pronouncement of judgment and verdict, questions of appeal...... scientific activities conducted by the author, partly based on the author's experience as a member, through a number of years, of the Danish Standing Committee on Procedural Law (Retsplejeraadet), which on a continuous basis evaluates the need for civil procedural reforms in Denmark, and finally also based...

  2. Decision-making Procedures

    DEFF Research Database (Denmark)

    Aldashev, Gani; Kirchsteiger, Georg; Sebald, Alexander Christopher

    2009-01-01

    It is a persistent finding in psychology and experimental economics that people's behavior is not only shaped by outcomes but also by decision-making procedures. In this paper we develop a general framework capable of modelling these procedural concerns. Within the context of psychological games we...... define procedures as mechanisms that influence the probabilities of reaching different endnodes. We show that for such procedural games a sequential psychological equilibrium always exists. Applying this approach within a principal-agent context we show that the way less attractive jobs are allocated...

  3. Constraint-Checking Editor for Procedure Tracking (ConCEPT), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Constructing, maintaining, and adapting operational procedures for manned space operations is a complex task, requiring the procedure author to satisfy constraints...

  4. Constraint-Checking Editor for Procedure Tracking (ConCEPT) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Constructing, maintaining, and adapting operational procedures for manned space operations is a complex task, requiring the procedure author to satisfy constraints...

  5. Surface Environmental Surveillance Procedures Manual

    International Nuclear Information System (INIS)

    Hanf, Robert W.; Poston, Ted M.

    2000-01-01

    Shows and explains certain procedures needed for surface environmental surveillance. Hanford Site environmental surveillance is conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy (DOE) under the Surface Environmental Surveillance Project (SESP). The basic requirements for site surveillance are set fourth in DOE Order 5400.1, General Environmental Protection Program Requirements. Guidance for the SESP is provided in DOE Order 5484.1, Environmental Protection, Safety, and Health Protection Information Reporting Requirements and DOE Order 5400.5, Radiation Protection of the Public and Environment. Guidelines for environmental surveillance activities are provided in DOE/EH-0173T, Environmental Regulatory Guide for Radiological Effluent Monitoring and Environmental Surveillance. An environmental monitoring plan for the Hanford Site is outlined in DOE/RL 91-50 Rev. 2, Environmental Monitoring Plan, United States Department of Energy, Richland Operations Office. Environmental surveillance data are used in assessing the impact of current and past site operations on human health and the environment, demonstrating compliance with applicable local, state, and federal environmental regulations, and verifying the adequacy of containment and effluent controls. SESP sampling schedules are reviewed, revised, and published each calendar year in the Hanford Site Environmental Surveillance Master Sampling Schedule. Environmental samples are collected by SESP staff in accordance with the approved sample collection procedures documented in this manual. Personnel training requirements are documented in SESP-TP-01 Rev.2, Surface Environmental Surveillance Project Training Program.

  6. Interventional procedures in the chest.

    Science.gov (United States)

    Vollmer Torrubiano, I; Sánchez González, M

    2016-05-01

    Many thoracic conditions will require an interventional procedure for diagnosis and/or treatment. For this reason, radiologists need to know the indications and the technique for each procedure. In this article, we review the various interventional procedures that radiologists should know and the indications for each procedure. We place special emphasis on the potential differences in the diagnostic results and complications between fine-needle aspiration and biopsy. We also discuss the indications for radiofrequency ablation of lung tumors and review the concepts related to the drainage of pulmonary abscesses. We devote special attention to the management of pleural effusion, covering the indications for thoracocentesis and when to use imaging guidance, and to the protocol for pleural drainage. We also discuss the indications for percutaneous treatment of pericardial effusion and the possible complications of this treatment. Finally, we discuss the interventional management of mediastinal lesions and provide practical advice about how to approach these lesions to avoid serious complications. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  7. Bariatric Surgery Procedures

    Science.gov (United States)

    ... Procedures Who is a Candidate for Bariatric Surgery? Childhood and Adolescent Obesity Find a Provider Benefits of Bariatric Surgery Life ... Bariatric Surgery FAQs Bariatric Surgery Procedures BMI Calculator Childhood and Adolescent Obesity 100 SW 75th Street, Suite 201, Gainesville, FL, ...

  8. MUSE optical alignment procedure

    Science.gov (United States)

    Laurent, Florence; Renault, Edgard; Loupias, Magali; Kosmalski, Johan; Anwand, Heiko; Bacon, Roland; Boudon, Didier; Caillier, Patrick; Daguisé, Eric; Dubois, Jean-Pierre; Dupuy, Christophe; Kelz, Andreas; Lizon, Jean-Louis; Nicklas, Harald; Parès, Laurent; Remillieux, Alban; Seifert, Walter; Valentin, Hervé; Xu, Wenli

    2012-09-01

    MUSE (Multi Unit Spectroscopic Explorer) is a second generation VLT integral field spectrograph (1x1arcmin² Field of View) developed for the European Southern Observatory (ESO), operating in the visible wavelength range (0.465-0.93 μm). A consortium of seven institutes is currently assembling and testing MUSE in the Integration Hall of the Observatoire de Lyon for the Preliminary Acceptance in Europe, scheduled for 2013. MUSE is composed of several subsystems which are under the responsibility of each institute. The Fore Optics derotates and anamorphoses the image at the focal plane. A Splitting and Relay Optics feed the 24 identical Integral Field Units (IFU), that are mounted within a large monolithic instrument mechanical structure. Each IFU incorporates an image slicer, a fully refractive spectrograph with VPH-grating and a detector system connected to a global vacuum and cryogenic system. During 2011, all MUSE subsystems were integrated, aligned and tested independently in each institute. After validations, the systems were shipped to the P.I. institute at Lyon and were assembled in the Integration Hall This paper describes the end-to-end optical alignment procedure of the MUSE instrument. The design strategy, mixing an optical alignment by manufacturing (plug and play approach) and few adjustments on key components, is presented. We depict the alignment method for identifying the optical axis using several references located in pupil and image planes. All tools required to perform the global alignment between each subsystem are described. The success of this alignment approach is demonstrated by the good results for the MUSE image quality. MUSE commissioning at the VLT (Very Large Telescope) is planned for 2013.

  9. Safeguards management inspection procedures

    International Nuclear Information System (INIS)

    Barth, M.J.; Dunn, D.R.

    1984-08-01

    The objective of this inspection module is to independently assess the contributions of licensee management to overall safeguards systems performance. The inspector accomplishes this objective by comparing the licensee's safeguards management to both the 10 CFR, parts 70 and 73, requirements and to generally accepted management practices. The vehicle by which this comparison is to be made consists of assessment questions and key issues which point the inspector to areas of primary concern to the NRC and which raise additional issues for the purpose of exposing management ineffectiveness. Further insight into management effectiveness is obtained through those assessment questions specifically directed toward the licensee's safeguards system performance. If the quality of the safeguards is poor, then the inspector should strongly suspect that management's role is ineffective and should attempt to determine management's influence (or lack thereof) on the underlying safeguards deficiencies. (The converse is not necessarily true, however.) The assessment questions in essence provide an opportunity for the inspector to identify, to single out, and to probe further, questionable management practices. Specific issues, circumstances, and concerns which point to questionable or inappropriate practices should be explicitly identified and referenced against the CFR and the assessment questions. The inspection report should also explain why the inspector feels certain management practices are poor, counter to the CFR, and/or point to ineffecive management. Concurrent with documenting the inspection results, the inspector should provide recommendations for alleviating observed management practices that are detrimental to effective safeguards. The recommendations could include: specific changes in the practices of the licensee, followup procedures on the part of NRC, and proposed license changes

  10. Reforming Russian Civil Procedur

    Directory of Open Access Journals (Sweden)

    Dmitry Maleshin

    2016-01-01

    Full Text Available The II Annual Symposium of the journal Herald of Civil Procedure ‘2015: The Civil Procedure 2.0: Reform and Current State’ took place on October 9, 2015, at the Faculty of Law of Kazan (Volga region Federal University.The Symposium is now an established tradition for the University. In 2015 it brought together in Kazan eminent scholars of civil procedure from cities across the whole of Russia: Moscow, St. Petersburg, Saratov, Ekaterinburg, Omsk, Samara, Nizhnekamsk and others. This large-scale event attracted the attention not only of Russian scholars, but also of legal scholars from abroad: Elisabetta Silvestri (Professor, University of Pavia, Italy, William B. Simons (Professor, University of Tartu, Estonia, Jaroslav Turlukovsky (Professor, Warsaw University, Poland, Stuart H. Schultz (Practising Attorney, USA, Irina Izarova (Associate Professor, Taras Shevchenko National University of Kyiv, Ukraine.The opening ceremony of the Symposium began with greetings to all participants and best wishes for productive discussions. Participants were welcomed with remarks by Marat Khairullin, Deputy Chair of the Supreme Court of the Republic of Tatarstan, Radik Ilyasov, Head of the Federal Bailiff Service of the Republic of Tatarstan, and Ildar Tarkhanov, Academic Supervisor at the Faculty of Law. They expressed their appreciation for the great value of the journal Herald of Civil Procedure in the growth of the science of civil procedure and enforcement procedure, and for its contributions to the development of the judicial system of the Russian Federation.In addition to hearing prepared reports and discussing viewpoints on current issues of civil and arbitration procedure, participants attended presentations by representatives from procedural law periodicals in the frame of the Symposium. The Editor-in-Chief of Herald of Civil Procedure, Damir Valeev, and the Commercial Director of the Statut Publishing House (Moscow, Kirill Samoilov, presented new

  11. Play vs. Procedures

    DEFF Research Database (Denmark)

    Hammar, Emil

    Through the theories of play by Gadamer (2004) and Henricks (2006), I will show how the relationship between play and game can be understood as dialectic and disruptive, thus challenging understandings of how the procedures of games determine player activity and vice versa. As such, I posit some...... analytical consequences for understandings of digital games as procedurally fixed (Boghost, 2006; Flannagan, 2009; Bathwaite & Sharp, 2010). That is, if digital games are argued to be procedurally fixed and if play is an appropriative and dialectic activity, then it could be argued that the latter affects...... and alters the former, and vice versa. Consequently, if the appointed procedures of a game are no longer fixed and rigid in their conveyance of meaning, qua the appropriative and dissolving nature of play, then understandings of games as conveying a fixed meaning through their procedures are inadequate...

  12. A multicentre, prospective, non-randomized, sequential, open-label trial to demonstrate the bioequivalence between intravenous immunoglobulin new generation (IGNG) and standard IV immunoglobulin (IVIG) in adult patients with primary immunodeficiency (PID).

    Science.gov (United States)

    Viallard, J-F; Brion, J-P; Malphettes, M; Durieu, I; Gardembas, M; Schleinitz, N; Hoarau, C; Lazaro, E; Puget, S

    2017-09-01

    To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE ® and ClairYg ® , a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg ® . Twenty-two adult PID patients receiving stable doses of TEGELINE ® (5% lyophilized IVIG) were switched to ClairYg ® for 6 months. ClairYg ® was administered under the same conditions as TEGELINE ® , either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg ® versus TEGELINE ® . Clinical efficacy was also assessed in terms of infections and associated events. Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE ® and 9.17g/L with ClairYg ® (i.e. geometric mean for the difference between ClairYg ® and TEGELINE ® was 1.136; [90% CI: 1.092-1.181] P4-6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg ® . The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE ® and 4.30 [0; 15.1] for ClairYg ® . Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg ® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg ® pharmacokinetics profile was comparable to that of TEGELINE ® . ClairYg ® is safe and effective in the treatment of adult PID. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  13. Radiological Work Planning and Procedures

    International Nuclear Information System (INIS)

    KURTZ, J.E.

    2000-01-01

    Each facility is tasked with maintaining personnel radiation exposure as low as reasonably achievable (ALARA). A continued effort is required to meet this goal by developing and implementing improvements to technical work documents (TWDs) and work performance. A review of selected TWDs from most facilities shows there is a need to incorporate more radiological control requirements into the TWD. The Radioactive Work Permit (RWP) provides a mechanism to place some of the requirements but does not provide all the information needed by the worker as he/she is accomplishing the steps of the TWD. Requiring the engineers, planners and procedure writers to put the radiological control requirements in the work steps would be very easy if all personnel had a strong background in radiological work planning and radiological controls. Unfortunately, many of these personnel do not have the background necessary to include these requirements without assistance by the Radiological Control organization at each facility. In addition, there seems to be confusion as to what should be and what should not be included in the TWD

  14. Reforming Russian civil Procedure

    OpenAIRE

    MALESHIN DMITRY; SILVESTRI ELISABETTA; SITDIKOV RUSLAN; VALEEV DAMIR

    2016-01-01

    The II Annual symposium of the journal Herald of Civil Procedure ‘2015: the Civil Procedure 2.0: reform and Current state’took place on october 9, 2015, at the Faculty of Law of kazan (Volga region) Federal university. the symposium is now an established tradition for the university. In 2015 it brought together in kazan eminent scholars of civil procedure from cities across the whole of russia: Moscow, st. Petersburg, saratov, Ekaterinburg, omsk, samara, Nizhnekamsk and others. this large-sca...

  15. Reforming Russian Civil Procedur

    OpenAIRE

    Dmitry Maleshin; Elisabetta Silvestri; Ruslan Sitgikov; Damir Valeev

    2016-01-01

    The II Annual Symposium of the journal Herald of Civil Procedure ‘2015: The Civil Procedure 2.0: Reform and Current State’ took place on October 9, 2015, at the Faculty of Law of Kazan (Volga region) Federal University.The Symposium is now an established tradition for the University. In 2015 it brought together in Kazan eminent scholars of civil procedure from cities across the whole of Russia: Moscow, St. Petersburg, Saratov, Ekaterinburg, Omsk, Samara, Nizhnekamsk and others. This large-sca...

  16. Law of procedure

    International Nuclear Information System (INIS)

    Witt, S. de.

    1984-01-01

    The real protection of fundamental rights of the population does not only depend on the substantive concretization in the atomic energy law but also on its procedural shaping. The more the citizens are burdened by governmental decisions the more decidedly it is requested not only by the principle of democracy, but also by the principle of law, that the parties concerned participate intensively in the procedure. In this second contribution De Witt describes the atomic energy licensing procedure and compares it with this claim. (orig./HSCH) [de

  17. Helicopter Fatigue. A Review of Current Requirements and Substantiation Procedures

    Science.gov (United States)

    1979-01-01

    d~montr6 math6matiquement, nous avons jusqu’alors calcul6 Ica, dur~es de vie avec les m~thodes classiques expos6es plus haut et dont la validit6 d et6...es de mise en service de nouveaux ~ mat~riels. Les bras ext~rieurs de nos moyeux en mat~z’ieu stratifies ont 6t6 optimis~s pour assurer Ie meilleur...HELICOPTERES 1 -INTRODUCTION Les m~thodes de justification A la ratigue des piaces d’h~licopt~res n’ont guare 6volu6 depuis une dizaine d’ann~es A

  18. 30 CFR 36.6 - Application procedures and requirements.

    Science.gov (United States)

    2010-07-01

    ... diesel engine, including joints and gaskets; the turbulence or precombustion chamber, if applicable..., fuel-injection pump, and mechanical governor assembly. All components shall be identified to permit... application. The form shall direct attention to the points that must be checked to make certain that all...

  19. Procedure for taking physical inventories

    International Nuclear Information System (INIS)

    Boston, R.A.

    1984-01-01

    Physical inventories are taken periodically to meet Company, State and IAEA requirements. Those physical inventories may be verified by IAEA and/or State inspectors. This presentation describes in an introductory but detailed manner the approaches and procedures used in planning, preparing, conducting, reconciling and reporting physical inventories for the Model Plant. Physical inventories are taken for plant accounting purposes to provide an accurate basis for starting and closing the plant material balance. Physical inventories are also taken for safeguards purposes to provide positive assurance that the nuclear materials of concern are indeed present and accounted for

  20. 45 CFR 1644.5 - Recipient policies and procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1644.5 Section... DISCLOSURE OF CASE INFORMATION § 1644.5 Recipient policies and procedures. Each recipient shall adopt written policies and procedures to implement the requirements of this part. ...

  1. 77 FR 30241 - Representation Procedures and Rulemaking Authority

    Science.gov (United States)

    2012-05-22

    ... the informal rulemaking procedures in the Administrative Procedure Act (APA), 5 U.S.C. 553, and... stricter requirements in sections 556 and 557 of the APA, this hearing will comply with those informal rulemaking procedures under the APA. See, e.g. United States v. Allegheny-Ludlum Steel Corp., 406 US 742...

  2. 10 CFR 76.72 - Miscellaneous procedural matters.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Miscellaneous procedural matters. 76.72 Section 76.72... § 76.72 Miscellaneous procedural matters. (a) The filing of any petitions for review or any responses to these petitions are governed by the procedural requirements set forth in 10 CFR 2.302(a) and (c...

  3. 10 CFR 72.150 - Instructions, procedures, and drawings.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Instructions, procedures, and drawings. 72.150 Section 72... WASTE Quality Assurance § 72.150 Instructions, procedures, and drawings. The licensee, applicant for a... documented instructions, procedures, or drawings of a type appropriate to the circumstances and shall require...

  4. 10 CFR 71.111 - Instructions, procedures, and drawings.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Instructions, procedures, and drawings. 71.111 Section 71... MATERIAL Quality Assurance § 71.111 Instructions, procedures, and drawings. The licensee, certificate..., procedures, or drawings of a type appropriate to the circumstances and shall require that these instructions...

  5. 20 CFR 636.5 - Exhaustion of grantee level procedure.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Exhaustion of grantee level procedure. 636.5..., INVESTIGATIONS AND HEARINGS § 636.5 Exhaustion of grantee level procedure. (a) Exhaustion required. No... have been exhausted. (b) Exhaustion exceptions. Complainants who have not exhausted the procedures at...

  6. Soil Sampling Operating Procedure

    Science.gov (United States)

    EPA Region 4 Science and Ecosystem Support Division (SESD) document that describes general and specific procedures, methods, and considerations when collecting soil samples for field screening or laboratory analysis.

  7. Cardiac Procedures and Surgeries

    Science.gov (United States)

    ... the Procedure Does A stent is a wire mesh tube used to prop open an artery during ... a Heart Attack • Heart Attack Tools & Resources • Support Network Heart Attack Tools & Resources My Cardiac Coach What ...

  8. Cosmetic Procedure Questions

    Science.gov (United States)

    ... for Every Season How to Choose the Best Skin Care Products In This Section Dermatologic Surgery What is dermatologic ... for Every Season How to Choose the Best Skin Care Products Cosmetic Procedure Questions Want to look younger? Start ...

  9. Dynamic alarm response procedures

    International Nuclear Information System (INIS)

    Martin, J.; Gordon, P.; Fitch, K.

    2006-01-01

    The Dynamic Alarm Response Procedure (DARP) system provides a robust, Web-based alternative to existing hard-copy alarm response procedures. This paperless system improves performance by eliminating time wasted looking up paper procedures by number, looking up plant process values and equipment and component status at graphical display or panels, and maintenance of the procedures. Because it is a Web-based system, it is platform independent. DARP's can be served from any Web server that supports CGI scripting, such as Apache R , IIS R , TclHTTPD, and others. DARP pages can be viewed in any Web browser that supports Javascript and Scalable Vector Graphics (SVG), such as Netscape R , Microsoft Internet Explorer R , Mozilla Firefox R , Opera R , and others. (authors)

  10. Assisted Medical Procedures (AMP)

    Data.gov (United States)

    National Aeronautics and Space Administration — DOCUMENTATION, DEVELOPMENT, AND PROGRESS The AMP was initially being developed as part the Advanced Integrated Clinical System (AICS)-Guided Medical Procedure System...

  11. EML procedures manual

    International Nuclear Information System (INIS)

    Volchok, H.L.; de Planque, G.

    1982-01-01

    This manual contains the procedures that are used currently by the Environmental Measurements Laboratory of the US Department of Energy. In addition a number of analytical methods from other laboratories have been included. These were tested for reliability at the Battelle, Pacific Northwest Laboratory under contract with the Division of Biomedical and Environmental Research of the AEC. These methods are clearly distinguished. The manual is prepared in loose leaf form to facilitate revision of the procedures and inclusion of additional procedures or data sheets. Anyone receiving the manual through EML should receive this additional material automatically. The contents are as follows: (1) general; (2) sampling; (3) field measurements; (4) general analytical chemistry; (5) chemical procedures; (6) data section; (7) specifications

  12. Canalith Repositioning Procedure

    Science.gov (United States)

    ... Overview The canalith repositioning procedure can help relieve benign paroxysmal positional vertigo (BPPV), a condition in which you have brief, but ... the inner ear responsible for balance (vestibular labyrinth). BPPV occurs when tiny particles called otoconia in one ...

  13. Nuclear materials management procedures

    International Nuclear Information System (INIS)

    Veevers, K.; Silver, J.M.; Quealy, K.J.; Steege, E. van der.

    1987-10-01

    This manual describes the procedures for the management of nuclear materials and associated materials at the Lucas Heights Research Laboratories. The procedures are designed to comply with Australia's nuclear non-proliferation obligations to the International Atomic Energy Agency (IAEA), bilateral agreements with other countries and ANSTO's responsibilities under the Nuclear Non-Proliferation (Safeguards) Act, 1987. The manual replaces those issued by the Australian Atomic Energy Commission in 1959, 1960 and 1969

  14. ASPECTOS ÉTICOS DE LOS ESTUDIOS DE BIODISPONIBILIDAD Y BIOEQUIVALENCIA DE PRODUCTOS FARMACÉUTICOS CONTENIDOS EN LAS LEGISLACIONES DE AMÉRICA LATINA ASPECTOS ÉTICOS DOS ESTUDOS DE BIODISPONIBILIDADE E BIOEQUIVALÊNCIA DE PRODUTOS FARMACÊUTICOS CONSTANTES NAS LEGISLAÇÕES DA AMÉRICA LATINA INVESTIGATIONS’ ETHICAL ASPECTS REGARDING PHARMACEUTICAL PRODUCTS’ BIODISPONIBILITY AND BIOEQUIVALENCE IN LATIN AMERICAN LEGISLATIONS

    Directory of Open Access Journals (Sweden)

    Luis Moreno Exebio

    2004-01-01

    certain countries with uptodate norms on biodisponibility/bioequivalence, and to determine if such criteria really protect participants in these investigations. In order to obtain information a questionnaire on biodisponibility/bioequivalence topics was sent via email to the medicaments’ regulating agencies in Argentina, Bolivia, Brasil, Chile, Colombia, Costa Rica, Ecuador, México, Paraguay, Perú, Uruguay and Venezuela. Conclusions show that uptodate norms regarding necessary ethical aspects to protect people who participate in those investigations are unequal Ethical requirements should be uniformed so as to allow a quicker legislation development in those countries that still lack it. This would also strengthen the region’s pharmacaeutical regulations

  15. Health Code Number (HCN) Development Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Petrocchi, Rocky; Craig, Douglas K.; Bond, Jayne-Anne; Trott, Donna M.; Yu, Xiao-Ying

    2013-09-01

    This report provides the detailed description of health code numbers (HCNs) and the procedure of how each HCN is assigned. It contains many guidelines and rationales of HCNs. HCNs are used in the chemical mixture methodology (CMM), a method recommended by the department of energy (DOE) for assessing health effects as a result of exposures to airborne aerosols in an emergency. The procedure is a useful tool for proficient HCN code developers. Intense training and quality assurance with qualified HCN developers are required before an individual comprehends the procedure to develop HCNs for DOE.

  16. 14 CFR 151.119 - Advance planning proposals: Procedures; funding.

    Science.gov (United States)

    2010-01-01

    ... TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Rules and Procedures for Advance Planning and... required by § 151.23, except the last sentence, also is required in connection with an advance planning...

  17. Environmental Requirements Management

    Energy Technology Data Exchange (ETDEWEB)

    Cusack, Laura J.; Bramson, Jeffrey E.; Archuleta, Jose A.; Frey, Jeffrey A.

    2015-01-08

    CH2M HILL Plateau Remediation Company (CH2M HILL) is the U.S. Department of Energy (DOE) prime contractor responsible for the environmental cleanup of the Hanford Site Central Plateau. As part of this responsibility, the CH2M HILL is faced with the task of complying with thousands of environmental requirements which originate from over 200 federal, state, and local laws and regulations, DOE Orders, waste management and effluent discharge permits, Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) response and Resource Conservation and Recovery Act (RCRA) corrective action documents, and official regulatory agency correspondence. The challenge is to manage this vast number of requirements to ensure they are appropriately and effectively integrated into CH2M HILL operations. Ensuring compliance with a large number of environmental requirements relies on an organization’s ability to identify, evaluate, communicate, and verify those requirements. To ensure that compliance is maintained, all changes need to be tracked. The CH2M HILL identified that the existing system used to manage environmental requirements was difficult to maintain and that improvements should be made to increase functionality. CH2M HILL established an environmental requirements management procedure and tools to assure that all environmental requirements are effectively and efficiently managed. Having a complete and accurate set of environmental requirements applicable to CH2M HILL operations will promote a more efficient approach to: • Communicating requirements • Planning work • Maintaining work controls • Maintaining compliance

  18. INADMISSIBLE EVIDENCE IN CIVIL PROCEDURE

    Directory of Open Access Journals (Sweden)

    Mihajlo Dika

    2016-01-01

    Full Text Available This paper examines the exclusion of specific means of evidence as instruments for determining the object of evidence, as well as the taking of evidence in the framework of the Croatian civil procedure law. The introduction lays the grounds for classifying and qualifying exclusion of evidence (general, special; absolute, relative; removable, irremovable; direct, indirect, after which greater attention is paid to the so called absolute and relative type; exclusionary evidence of the direct relative type pertaining to the establishing of facts, and evidence dismissals. With regard to the indirect relative type, the paper examines exclusionary evidence concerning the object of evidence. The remainder of the paper focuses on illegally obtained evidence, while outlining the constitutional, statutory, judicature and doctrinaire premises of bearing for such evidence. Subsequently, the question of evidence obtained in violation of the Constitutional guarantee of respect and legal protection of private and family life, dignity, reputation and honour, as well as evidence obtained by breach of the Constitutional guarantee of freedom and secrecy of correspondence and all other forms of communication, and in violation of the right to safety and privacy of personal data, are discussed too. In addition, the paper analyses the institutions of preclusion of evidence and the so called informative evidence. Concluding, the author points to a lacking regulation of inadmissible evidence within the Croatian civil procedure law, underlining the need to determine de lege ferenda legal requirements with a view to operationalizing inadmissible evidence within the Croatian civil procedure law.

  19. Operating procedures and safety culture

    International Nuclear Information System (INIS)

    Carnino, A.

    1993-01-01

    The development of new technologies in recent years has led to a tremendous increase in the information to be mastered by operators in industrial processes. The information at operators disposal both in routine situations and accidental ones needs to be well prepared and organized to ensure reliability and safety. The man-machine interface should give operators all the necessary and clear indications on the process status and evolution so that the operators can operate the installation through adequate procedures. Procedures represent the real interface and mode of action of the operators on the machine, and they are of prime importance. Although they are by essence quite different, the routine, accident, and emergency procedures have in common one attribute: They all require a good safety culture both in their development and their implementation. From the definition given by the members of the International Nuclear Safety Advisory Group (INSAG), open-quotes Safety culture is that assembly of characteristics and attitudes in organizations and individuals which establishes that, as an overriding priority, nuclear plant safety issues receive the attention warranted by their significance,close quotes one can see that two aspects are embedded, a collective attitude that in fact is reflected in the managerial framework and an individual one that is linked to personnel behavior and work practices

  20. Procedures for ground-water investigations

    International Nuclear Information System (INIS)

    1989-09-01

    This manual was developed by the Pacific Northwest Laboratory (PNL) to document the procedures used to carry out and control the technical aspects of ground-water investigations at the PNL. Ground-water investigations are carried out to fulfill the requirements for the US Department of Energy (DOE) to meet the requirements of DOE Orders. Investigations are also performed for various clients to meet the requirements of the Resource Conservation and Recovery Act of 1976 (RCRA) and the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (CERCLA). National standards including procedures published by the American Society for Testing and Materials (ASTM) and the US Geological Survey were utilized in developing the procedures contained in this manual

  1. Requirements Engineering

    CERN Document Server

    Hull, Elizabeth; Dick, Jeremy

    2011-01-01

    Written for those who want to develop their knowledge of requirements engineering process, whether practitioners or students.Using the latest research and driven by practical experience from industry, Requirements Engineering gives useful hints to practitioners on how to write and structure requirements. It explains the importance of Systems Engineering and the creation of effective solutions to problems. It describes the underlying representations used in system modeling and introduces the UML2, and considers the relationship between requirements and modeling. Covering a generic multi-layer r

  2. Software requirements

    CERN Document Server

    Wiegers, Karl E

    2003-01-01

    Without formal, verifiable software requirements-and an effective system for managing them-the programs that developers think they've agreed to build often will not be the same products their customers are expecting. In SOFTWARE REQUIREMENTS, Second Edition, requirements engineering authority Karl Wiegers amplifies the best practices presented in his original award-winning text?now a mainstay for anyone participating in the software development process. In this book, you'll discover effective techniques for managing the requirements engineering process all the way through the development cy

  3. Health and Safety Procedures Manual for hazardous waste sites

    Energy Technology Data Exchange (ETDEWEB)

    Thate, J.E.

    1992-09-01

    The Oak Ridge National Laboratory Chemical Assessments Team (ORNL/CAT) has developed this Health and Safety Procedures Manual for the guidance, instruction, and protection of ORNL/CAT personnel expected to be involved in hazardous waste site assessments and remedial actions. This manual addresses general and site-specific concerns for protecting personnel, the general public, and the environment from any possible hazardous exposures. The components of this manual include: medical surveillance, guidance for determination and monitoring of hazards, personnel and training requirements, protective clothing and equipment requirements, procedures for controlling work functions, procedures for handling emergency response situations, decontamination procedures for personnel and equipment, associated legal requirements, and safe drilling practices.

  4. Robot-assisted procedures in pediatric neurosurgery.

    Science.gov (United States)

    De Benedictis, Alessandro; Trezza, Andrea; Carai, Andrea; Genovese, Elisabetta; Procaccini, Emidio; Messina, Raffaella; Randi, Franco; Cossu, Silvia; Esposito, Giacomo; Palma, Paolo; Amante, Paolina; Rizzi, Michele; Marras, Carlo Efisio

    2017-05-01

    OBJECTIVE During the last 3 decades, robotic technology has rapidly spread across several surgical fields due to the continuous evolution of its versatility, stability, dexterity, and haptic properties. Neurosurgery pioneered the development of robotics, with the aim of improving the quality of several procedures requiring a high degree of accuracy and safety. Moreover, robot-guided approaches are of special interest in pediatric patients, who often have altered anatomy and challenging relationships between the diseased and eloquent structures. Nevertheless, the use of robots has been rarely reported in children. In this work, the authors describe their experience using the ROSA device (Robotized Stereotactic Assistant) in the neurosurgical management of a pediatric population. METHODS Between 2011 and 2016, 116 children underwent ROSA-assisted procedures for a variety of diseases (epilepsy, brain tumors, intra- or extraventricular and tumor cysts, obstructive hydrocephalus, and movement and behavioral disorders). Each patient received accurate preoperative planning of optimal trajectories, intraoperative frameless registration, surgical treatment using specific instruments held by the robotic arm, and postoperative CT or MR imaging. RESULTS The authors performed 128 consecutive surgeries, including implantation of 386 electrodes for stereo-electroencephalography (36 procedures), neuroendoscopy (42 procedures), stereotactic biopsy (26 procedures), pallidotomy (12 procedures), shunt placement (6 procedures), deep brain stimulation procedures (3 procedures), and stereotactic cyst aspiration (3 procedures). For each procedure, the authors analyzed and discussed accuracy, timing, and complications. CONCLUSIONS To the best their knowledge, the authors present the largest reported series of pediatric neurosurgical cases assisted by robotic support. The ROSA system provided improved safety and feasibility of minimally invasive approaches, thus optimizing the surgical

  5. Geologic mapping procedure: Final draft

    International Nuclear Information System (INIS)

    1987-09-01

    Geologic mapping will provide a baseline record of the subsurface geology in the shafts and drifts of the Exploratory Shaft Facility (ESF). This information will be essential in confirming the specific repository horizon, selecting representative locations for the in situ tests, providing information for construction and decommissioning seal designs, documenting the excavation effects, and in providing information for performance assessment, which relates to the ultimate suitability of the site as a nuclear waste repository. Geologic mapping will be undertaken on the walls and roof, and locally on the floor within the completed At-Depth Facility (ADF) and on the walls of the two access shafts. Periodic mapping of the exposed face may be conducted during construction of the ADF. The mapping will be oriented toward the collection and presentation of geologic information in an engineering format and the portrayal of detailed stratigraphic information which may be useful in confirmation of drillhole data collected as part of the surface-based testing program. Geologic mapping can be considered as a predictive tool as well as a means of checking design assumptions. This document provides a description of the required procedures for geologic mapping for the ESF. Included in this procedure is information that qualified technical personnel can use to collect the required types of geologic descriptions, at the appropriate level of detail. 5 refs., 3 figs., 1 tab

  6. PROCEDURAL CONVENTION AND FLEXIBILITY OF THE PROCED URE: THE INFLUENCE OF PRIVATE AUTONOMY ON THE PUBLICIST PARADIGM OF CIVIL PROCEDURE

    Directory of Open Access Journals (Sweden)

    Marcelo Dias Ponte

    2015-12-01

    Full Text Available The research aims to analyze the New CPC innovations with regard to the procedural legal business, to assess, carefully, it s possibilities, its limits, requirements and the function of the court and the parties to the flexibility of the procedure. The study approaches the shared management of the procedure, the procedural calendar as materializing institute the principle of efficiency. As a result, it was found that procedural conventions have the power to better protect the substantive rights involved in the dispute, since the litigants may bring the procedural rite to the needs of the conflict, allowing a view democratic demand, able to increase dialogue and interaction between the parties.

  7. Methods for testing the logical structure of plant procedure documents

    International Nuclear Information System (INIS)

    Horne, C.P.; Colley, R.; Fahley, J.M.

    1990-01-01

    This paper describes an ongoing EPRI project to investigate computer based methods to improve the development, maintenance, and verification of plant operating procedures. This project began as an evaluation of the applicability of structured software analysis methods to operating procedures. It was found that these methods offer benefits, if procedures are transformed to a structured representation to make them amenable to computer analysis. The next task was to investigate methods to transform procedures into a structured representation. The use of natural language techniques to read and compile the procedure documents appears to be viable for this purpose and supports conformity to guidelines. The final task was to consider possibilities of automated verification methods for procedures. Methods to help verify procedures were defined and information requirements specified. These methods take the structured representation of procedures as input. The software system being constructed in this project is called PASS, standing for Procedures Analysis Software System

  8. Generic drugs: myths, facts, and limitations

    Directory of Open Access Journals (Sweden)

    Antonio Marzo

    2012-10-01

    Full Text Available Bioequivalence (BE has always been an important pharmaceutical area, particularly (but not solely in Mediterranean region, where the use of generic drugs is a relatively recent development. The lack of new therapeutic molecules has concentrated primary research in the hands of a few large pharmaceutical companies. For smaller companies, this has created opportunities for the development of new formulations of existing drugs (orodispersible tablets that dissolve in the mouth, extended-release tablets, transdermal delivery systems, generic drugs. These applications take advantage of the Abridged New Drug Application (ANDA procedure, which exempts them from a series of expensive investigations and limits the requirement for clinical testing to bioequivalence trials. Since 1991, bioequivalence trials have been regulated by US Food and Drug Administration (FDA and European Medicines Agency (EMA guidelines that provide precise indications on the most specific procedures to be adopted. In spite of these guidelines, however, some aspects of the process have not been fully defined, the most important of which regards the management of endogenous substances. Additional problems are how to manage bioequivalence protocols with drugs that have long half-lives and those whose clearance is characterized by high intrinsic variability. The view that bioequivalence data would be more reliable if they were based on studies in target populations is a myth to be discredited. The present paper reviews issues relative to pharmacokinetics (PK, bioavailability (BA, and bioequivalence, also from an historical viewpoint, and includes a stimulating “questions and answers” section on some key aspects of the bioequivalence of generic drugs.

  9. Factoring humans into procedures

    International Nuclear Information System (INIS)

    Luna, S.F.; Sturdivant, M.H.; McKay, R.C.

    1988-01-01

    INPO statistics on reported events in nuclear power plants rank deficient procedures as the largest single cause of human performance errors. Human factors principles used to improve the effectiveness of the control room operator can also improve the usability of written procedures. This human factors approach treats each page or complement of pages as a display. Four techniques for applying this approach are reviewed in this paper: (1) presenting information in small blocks (or fields), (2) presenting information consistently, (3) using the mental templates of the performer, and (4) matching the physical features of the plant. A final section offers examples in which combinations of these techniques are used

  10. 76 FR 62092 - Filing Procedures

    Science.gov (United States)

    2011-10-06

    ... INTERNATIONAL TRADE COMMISSION Filing Procedures AGENCY: International Trade Commission. ACTION: Notice of issuance of Handbook on Filing Procedures. SUMMARY: The United States International Trade Commission (``Commission'') is issuing a Handbook on Filing Procedures to replace its Handbook on Electronic...

  11. The TOMAX-procedure

    NARCIS (Netherlands)

    Overgoor, M.L.E.

    2015-01-01

    Most patients with a low spinal lesion (LSL) have intact erectile function but no penile sensation, which can lead to frustration. To tackle this problem, we designed TOMAX, TOMAXimize sensation, sexuality and quality of life, a surgical procedure in which a functional "groin” nerve is connected to

  12. OCRWM international procedures

    International Nuclear Information System (INIS)

    1986-03-01

    These international procedures provide guidance and assistance for the Office of Civilian Radioactive Waste Management (OCRWM) and for OCRWM Project Offices, contractors and subcontractors in conducting international activities. They supplement the relevant Department of Energy (DOE) orders (which are referenced), not supplant them

  13. 3. Procedures and Recursion

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 6. Algorithms Procedures and Recursion. R K Shyamasundar. Series Article Volume 1 ... Author Affiliations. R K Shyamasundar1. Computer Science Group, Tata Institute of Fundamental Research, Homi Bhabha Road Mumbai 400 005, India.

  14. Educational Accounting Procedures.

    Science.gov (United States)

    Tidwell, Sam B.

    This chapter of "Principles of School Business Management" reviews the functions, procedures, and reports with which school business officials must be familiar in order to interpret and make decisions regarding the school district's financial position. Among the accounting functions discussed are financial management, internal auditing,…

  15. IXM gas sampling procedure

    International Nuclear Information System (INIS)

    Pingel, L.A.

    1995-01-01

    Ion Exchange Modules (IXMs) are used at the 105-KE and -KW Fuel Storage Basins to control radionuclide concentrations in the water. A potential safety concern relates to production of hydrogen gas by radiolysis of the water trapped in the ion exchange media of spent IXMs. This document provides a procedure for sampling the gases in the head space of the IXM

  16. Formalizing physical security procedures

    NARCIS (Netherlands)

    Meadows, C.; Pavlovic, Dusko

    Although the problems of physical security emerged more than 10,000 years before the problems of computer security, no formal methods have been developed for them, and the solutions have been evolving slowly, mostly through social procedures. But as the traffic on physical and social networks is now

  17. Juveniles in criminal procedure

    Directory of Open Access Journals (Sweden)

    Lukić Tatjana

    2012-01-01

    Full Text Available Taking into consideration the importance and role of children in modern society, as well as their position, this article has as its focus juveniles in criminal procedure. The existence of a separate juvenile justice system independent of the criminal law applicable to the adult offenders and general criminal procedure, as well as the periodic changes of the dominant approach in theory and practice reflects the ascendancy of different theoretical perspectives in the juvenile justice. In this paper, the authors scrutinize the models of responding to juvenile crime - justice and welfare model - as two models of the greatest importance in the present reaction of the society to the crimes conducted by the youngest delinquents at the beginning of the new century and millennium. Furthermore, the paper deals with a matter of international legal standards which, to a large extent, give shape to the legal framework for juvenile offenders and provide their rights and position in the criminal procedure. The authors refer to the internationally accepted documents on several levels. From the (almost universally accepted multilateral conventions on human rights, through the field of recommendations, rules and guidelines which are obeyed and enforced in practice of the juvenile justice although they are of non-binding nature, via the regional European legislative to the national provisions in a particular number of countries. On all the levels mentioned above the rights of the juveniles are regulated having in mind their possible role in the criminal procedure as a perpetrator of a criminal act, as a victim or as a witness. This paper also analyzes the criminal procedure with respect to juvenile perpetrators of the criminal acts in the Republic of Serbia and compliance of the provisions currently in vigor with the international legal standards contained in the international conventions and other internationally accepted and recognized instruments.

  18. Contraindications and complications of the Latarjet procedure.

    Science.gov (United States)

    Domos, Peter; Lunini, Enricomaria; Walch, Gilles

    2018-01-01

    The Latarjet procedure is a well-known, safe and reliable technique to treat primary or recurrent anterior dislocations or subluxations, with or without hyperlaxity, with or without glenoid bone loss. Both the open and the arthroscopic methods produce excellent clinical results, with a low rate of recurrent instability. There have been concerns of a higher surgical complication rate associated with this procedure, however, large reviews reported an overall complication rate in the open Latarjet procedure of 15%. Meticulous surgical technique and a good understanding of the local anatomy can help to avoid the complications but postoperative shoulder arthritis and frequent bone block osteolysis remain unsolved additional challenges, which require further research. There are 2 main factors to further improve the clinical outcome and patient satisfaction: careful patient selection with good surgical indication, and reducing complications with adequate surgical techniques. The aim of this study is to provide the current overview of the contraindications and complications of the Latarjet procedure.

  19. Procedures for sampling radium-contaminated soils

    International Nuclear Information System (INIS)

    Fleischhauer, H.L.

    1985-10-01

    Two procedures for sampling the surface layer (0 to 15 centimeters) of radium-contaminated soil are recommended for use in remedial action projects. Both procedures adhere to the philosophy that soil samples should have constant geometry and constant volume in order to ensure uniformity. In the first procedure, a ''cookie cutter'' fashioned from pipe or steel plate, is driven to the desired depth by means of a slide hammer, and the sample extracted as a core or plug. The second procedure requires use of a template to outline the sampling area, from which the sample is obtained using a trowel or spoon. Sampling to the desired depth must then be performed incrementally. Selection of one procedure over the other is governed primarily by soil conditions, the cookie cutter being effective in nongravelly soils, and the template procedure appropriate for use in both gravelly and nongravelly soils. In any event, a minimum sample volume of 1000 cubic centimeters is recommended. The step-by-step procedures are accompanied by a description of the minimum requirements for sample documentation. Transport of the soil samples from the field is then addressed in a discussion of the federal regulations for shipping radioactive materials. Interpretation of those regulations, particularly in light of their application to remedial action soil-sampling programs, is provided in the form of guidance and suggested procedures. Due to the complex nature of the regulations, however, there is no guarantee that our interpretations of them are complete or entirely accurate. Preparation of soil samples for radium-226 analysis by means of gamma-ray spectroscopy is described

  20. 12 CFR 219.6 - Payment procedures.

    Science.gov (United States)

    2010-01-01

    ... obtain payment of costs incurred prior to the time the financial institution receives this notice. [Reg... PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S) Reimbursement to Financial Institutions for Providing Financial Records § 219.6 Payment procedures. (a) Notice...

  1. 78 FR 35812 - Revisions to Procedural Rules

    Science.gov (United States)

    2013-06-14

    ... (APA) ``provides agencies with broad discretion to fashion procedures that make the hearing process... appearance. 39 CFR 3001.21(c). The Commission is proposing to shorten that period by requiring that motions to strike testimony be filed at least 3 calendar days before a witness's scheduled appearance, unless...

  2. 7 CFR 220.11 - Reimbursement procedures.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE CHILD NUTRITION PROGRAMS SCHOOL BREAKFAST PROGRAM § 220.11 Reimbursement procedures. (a) To be... agency administers any combination of the Child Nutrition Programs, the SFA shall be able to use a common... served to children for 1 month. The State agency, or FNSRO where applicable, shall require School Food...

  3. Methods and procedures of succession of generations

    International Nuclear Information System (INIS)

    Homann, A.; Bendzko, R.

    2001-01-01

    The presentation describes the methods and procedures of the succession of generations in the nuclear industry. The industrial development required specialised knowledge and creativity on a changing level. The relations ship between knowledge-transfer and transfer of the responsibility must be taken into account. The knowledge-transfer has to be planned as an investment. (authors)

  4. Pharmacokinetic properties and bioequivalence of two compound formulations of 1500 mg ampicillin (1167 mg)/probenecid (333 mg): a randomized-sequence, single-dose, open-label, two-period crossover study in healthy Chinese male volunteers.

    Science.gov (United States)

    Wu, Huizhe; Liu, Mingyan; Wang, Shuang; Feng, Wanyu; Yao, Weifan; Zhao, Haishan; Wei, Minjie

    2010-03-01

    Ampicillin/probenecid is an antimicrobial formulation indicated for the treatment of respiratory, urinary tract, and gastrointestinal infections. Ampicillin sodium is the active antimicrobial ingredient that can act on the phase of bacterial breeding and inhibit the biosynthesis of bacterial mucopeptide in the cell wall. Probenecid acts synergistically by competitively inhibiting an organic anion transporter in renal tubules, increasing the plasma concentrations, and thus extending the plasma elimination t(1/2). The aim of this study was to assess and compare the pharmacokinetic (PK) properties, bioavailability, and bioequivalence of a newly developed dispersible tablet formulation (test) of ampicillin/ probenecid with those of an established branded capsule formulation (reference) in healthy Chinese male volunteers. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted healthy Chinese male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 6 dispersible tablets (test) or branded capsules (reference) (1500 mg total; 250 mg each containing ampicillin 194.5 mg and probenecid 55.5 mg), followed by a 7-day washout period and administration of the alternate formulation. Plasma samples were collected over a 24-hour period following administration and analyzed for ampicillin and probenecid content by HPLC. PK parameters such as C(max), AUC(0-t), and AUC(0-infinity) were also determined. The formulations were considered bioequivalent if the geometric mean ratios of the log-transformed C(max) and AUC values were within the equivalence range (80%-125%) predetermined by the State Food and Drug Administration (SFDA) of the People's Republic of China. Tolerability was based on the observation of adverse events (AEs), monitoring of vital signs (blood pressure, heart rate, temperature, electrocardiography) and laboratory tests (hematology, blood biochemistry, hepatic function, urinalysis), and subject

  5. Closure requirements

    International Nuclear Information System (INIS)

    Hutchinson, I.P.G.; Ellison, R.D.

    1992-01-01

    Closure of a waste management unit can be either permanent or temporary. Permanent closure may be due to: economic factors which make it uneconomical to mine the remaining minerals; depletion of mineral resources; physical site constraints that preclude further mining and beneficiation; environmental, regulatory or other requirements that make it uneconomical to continue to develop the resources. Temporary closure can occur for a period of several months to several years, and may be caused by factors such as: periods of high rainfall or snowfall which prevent mining and waste disposal; economic circumstances which temporarily make it uneconomical to mine the target mineral; labor problems requiring a cessation of operations for a period of time; construction activities that are required to upgrade project components such as the process facilities and waste management units; and mine or process plant failures that require extensive repairs. Permanent closure of a mine waste management unit involves the provision of durable surface containment features to protect the waters of the State in the long-term. Temporary closure may involve activities that range from ongoing maintenance of the existing facilities to the installation of several permanent closure features in order to reduce ongoing maintenance. This paper deals with the permanent closure features

  6. Headache and endovascular procedures.

    Science.gov (United States)

    de Biase, Stefano; Longoni, Marco; Gigli, Gian Luigi; Agostoni, Elio

    2017-05-01

    The International Classification of Headache Disorders (ICHD-3 beta) includes headache attributed to intracranial endovascular procedures (EVPs). The aim of this review is to describe the clinical and pathophysiological aspects of headache related to vascular lesions and EVPs. Current studies regarding this issue are contradictory, although generally favouring headache improvement after EVPs. Further large studies are needed to adequately assess the effect of EVPs on headache.

  7. Job Requirements System: Procedure for the Analysis of Occupationa Requirements Within Job Sets.

    Science.gov (United States)

    1991-12-01

    ASVAB Speed Coding Speeding ASVAB Number Operations ASVAB Spatial Object Rotation Test Project A Maze Test Project A Assembling Objects Test Project A...Limit (vis a vis (Minutes) ASVAB) Spatial Object Rotation Test 0.81 0.72 8 Maze Test 0.7’ 0.70 6 Assembling Objects Test 0.65 0.70 16 Orientation...1 awadu a, D® -3 IXA 0 0MAP x - a ~J - -_~e oxSw " E)maaq~m~ZA E ) Eaa~qfsp3() 0 4a E) 2 E)a (% U I) EVA &IV UM swmuduoomE dig __ dam" *Low *AWWl

  8. Procedure Study Guide (Revision)

    Science.gov (United States)

    1997-04-01

    FROM SERVICE RECORD- MARITAL STATUS NO. DEPENDENTS CONTRIBUTION TO FAMILY OR QTRS ALLOWANCE (Amount required by law) N/A PAY PER MONTH... FAMILY OR QTRS ALLOWANCE (Amount required by law) none PAY PER MONTH (Including sea or foreign duty pay, if any) $965.40 RECORD OF PREVIOUS...dismissed eight days after the accused enlisted.) In Russo, the accused suffered from dyslexia . The recruiter was advised of the accused’s inability

  9. Surface cleanliness measurement procedure

    Science.gov (United States)

    Schroder, Mark Stewart; Woodmansee, Donald Ernest; Beadie, Douglas Frank

    2002-01-01

    A procedure and tools for quantifying surface cleanliness are described. Cleanliness of a target surface is quantified by wiping a prescribed area of the surface with a flexible, bright white cloth swatch, preferably mounted on a special tool. The cloth picks up a substantial amount of any particulate surface contamination. The amount of contamination is determined by measuring the reflectivity loss of the cloth before and after wiping on the contaminated system and comparing that loss to a previous calibration with similar contamination. In the alternative, a visual comparison of the contaminated cloth to a contamination key provides an indication of the surface cleanliness.

  10. Dispersant field monitoring procedures

    International Nuclear Information System (INIS)

    Hillman, S. O.; Hood, S. D.; Bronson, M. T.; Shufelt, G.

    1997-01-01

    Alyeska Pipeline Service Company's (APSC) dispersant response capability in the Port of Valdez, Prince William Sound, and in the Gulf of Alaska was described. APSC provides dispersal equipment, aerial spray delivery systems, helibucket delivery systems, vessel delivery systems, along with a minimum of 600,000 gallon stockpile of the dispersant Corexit 9527. Effectiveness and effects are monitored by visual observation. In addition, fluorometer and water sample analysis are also used to provide field analytical data indicative of the environmental effects of dispersant applications. The field monitoring plan was field tested in December 1996. Details of the monitoring procedures are outlined in this paper. 18 refs., 5 tabs

  11. Quality procedure management for improved nuclear safety

    International Nuclear Information System (INIS)

    Forzano, P.; Castagna, P.

    1995-01-01

    Emergency Operating Procedures and Accident Management Procedures are the next step in the computerization of NPP control rooms. Different improvements are presently conceivable for this operator aid tool, and research activities are in development. Undergoing activities regard especially formal aspects of knowledge representation, Human-Machine interface and procedure life cycle management. These aspects have been investigated deeply by Ansaldo, and partially incorporated in the DIAM prototype. Nuclear Power Plant Procedures can be seen from essentially two viewpoints: the process and the information management. From the first point of view, it is important to supply the knowledge apt to solve problems connected with the control of the process, from the second one the focus of attention is on the knowledge representation, its structure, elicitation and maintenance, and formal quality assurance. These two aspects of procedure representation can be considered and solved separately. In particular, methodological, formal and management issues require long and tedious activities, that in most cases constitute a great barrier for procedures development and upgrade. To solve these problems, Ansaldo is developing DIAM, a wide integrated tool for procedure management to support in procedure writing, updating, usage, and documentation. One of the most challenging features of DIAM is AUTO-LAY, a CASE sub-tool that, in a complete automatical way, structures parts or complete flow diagram. This is the feature that is partial present in some other CASE products, that, anyway, do not allow complex graph handling and isomorphism between video and paper representation. AUTO-LAY has the unique prerogative to draw graphs of any complexity to section them in pages, and to automatically compose a document. This has been recognized in the literature as the most important a second-generation CASE improvement. (Author) 9 Figs., 5 Refs

  12. Critical care procedure logging using handheld computers.

    Science.gov (United States)

    Martinez-Motta, J Carlos; Walker, Robin; Stewart, Thomas E; Granton, John; Abrahamson, Simon; Lapinsky, Stephen E

    2004-10-01

    We conducted this study to evaluate the feasibility of implementing an internet-linked handheld computer procedure logging system in a critical care training program. Subspecialty trainees in the Interdepartmental Division of Critical Care at the University of Toronto received and were trained in the use of Palm handheld computers loaded with a customized program for logging critical care procedures. The procedures were entered into the handheld device using checkboxes and drop-down lists, and data were uploaded to a central database via the internet. To evaluate the feasibility of this system, we tracked the utilization of this data collection system. Benefits and disadvantages were assessed through surveys. All 11 trainees successfully uploaded data to the central database, but only six (55%) continued to upload data on a regular basis. The most common reason cited for not using the system pertained to initial technical problems with data uploading. From 1 July 2002 to 30 June 2003, a total of 914 procedures were logged. Significant variability was noted in the number of procedures logged by individual trainees (range 13-242). The database generated by regular users provided potentially useful information to the training program director regarding the scope and location of procedural training among the different rotations and hospitals. A handheld computer procedure logging system can be effectively used in a critical care training program. However, user acceptance was not uniform, and continued training and support are required to increase user acceptance. Such a procedure database may provide valuable information that may be used to optimize trainees' educational experience and to document clinical training experience for licensing and accreditation.

  13. Preanalytical requirements of urinalysis

    Science.gov (United States)

    Delanghe, Joris; Speeckaert, Marijn

    2014-01-01

    Urine may be a waste product, but it contains an enormous amount of information. Well-standardized procedures for collection, transport, sample preparation and analysis should become the basis of an effective diagnostic strategy for urinalysis. As reproducibility of urinalysis has been greatly improved due to recent technological progress, preanalytical requirements of urinalysis have gained importance and have become stricter. Since the patients themselves often sample urine specimens, urinalysis is very susceptible to preanalytical issues. Various sampling methods and inappropriate specimen transport can cause important preanalytical errors. The use of preservatives may be helpful for particular analytes. Unfortunately, a universal preservative that allows a complete urinalysis does not (yet) exist. The preanalytical aspects are also of major importance for newer applications (e.g. metabolomics). The present review deals with the current preanalytical problems and requirements for the most common urinary analytes. PMID:24627718

  14. Interventional spinal procedures

    Energy Technology Data Exchange (ETDEWEB)

    Andreula, Cosma E-mail: cosmaandreula@tin.it; Muto, Mario; Leonardi, Marco

    2004-05-01

    The interventional procedures for disk herniation and protrusion by percutaneous techniques are decompressive such as chemodiscolysis with chimopapain, nucleo-discectomy introduced by Onik, LASER discectomy, and recently nucleoplasty, and decompressive and direct antinflammatory such as chemiodiscolysis with an Oxygen-ozone mixture. These techniques have minimized the invasive nature of surgery and avoid or decrease complications like infection linked to surgery. Reducing intervertebral disc size by mechanical aspiration of a part of the disc or partially dissolving the herniation by drying reduces the conic pressure on the torn annulus and creates the space necessary for retropulsion whenever the circular fibres of the annulus regain a minimum capacity to contain the disc under tension. The proposed suggestion in these techniques is that a small change in volume produces large change in pressure. The success rates reported in different studies vary from 65 to 80% of excellent or good results with chemonucleolysis and aspiration. Vertebroplasty (VP) is done by percutaneous injection of acrylic cement (polymethylmetacrylate-PMMA) into the vertebrae under fluoroscopic and/or CT control to achieve an antalgic effect and stabilize the vertebral body. VP has been used for vertebral collapses caused by osteoporosis, long-term steroid treatment, aggressive symptomatic angiomas and lytic metastasis. The reported figures in literature are 80-95% of pain relief, within 7 days after procedure, commonly on the same day.

  15. Evidence in criminal procedure

    Directory of Open Access Journals (Sweden)

    Paolo Ferrua

    2018-03-01

    Full Text Available This paper analyzes the three components of the evidence operation: proof premises or evidence in the strict sense, with particular regard to the distinction between evidence declaration and critical/circumstantial evidence; the propositions to be proved, principal or incidental, final or intermediate; the act of proving, connoted by the rule of beyond all reasonable doubt. While the first two terms vary according to the procedural context, the third remains indefectible, since it is incongruous to consider any proposition to be 'proven' while there is a reasonable reason to doubt it. With regard to the distribution of the burden of proof, the structure of the case and its legal qualification, whether substantial or procedural, are decisive. Therefore, it is possible to identify, for each decision alternative, the term 'marked', which conveys the proposition to be proved, and the opposite 'consequential' term, which derives from the failure to reach the proof: for example, with respect to the main object in trial, the term 'marked' is the conviction, the term 'consequential' the acquittal.

  16. Regulations and Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Young, Lydia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2010-09-30

    The purpose of the Regulations and Procedures Manual (RPM) is to provide Laboratory personnel with a reference to University and Lawrence Berkeley National Laboratory policies and regulations by outlining the normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory departments. Much of the information in this manual has been condensed from detail provided in Laboratory procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. The sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the department responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which department should be called, please contact the Associate Laboratory Director of Operations.

  17. Metanálise de estudos de bioequivalência: a intercambiabilidade de genéricos e similares que contêm Hidroclorotiazida é possível, mas não àqueles com Maleato de Enalapril Meta-analysis for bioequivalence studies: interchangeability of generic drugs and similar containing Hydrochlorothiazide is possible but not with Enalapril Maleate

    Directory of Open Access Journals (Sweden)

    Renato Almeida Lopes

    2010-06-01

    -name and generic or similar drugs is necessary that they are bioequivalent. With the growing number of generic drugs, it is common for patients to replace a generic to another or one similar. However, this exchange can not guarantee the maintenance of bioequivalence. To evaluate the safety interchangeability between different generic and similar drugs with Hydrochlorothiazide and Enalapril Maleate, a meta-analysis was carried out with several bioequivalence studies with these drugs. METHODS: Data from bioequivalence of generic and similar drugs approved by the National Health Surveillance Agency (Anvisa (drug regulatory agency in Brazil were used. The compatibility of data from each study was analyzed and the determination of a confidence interval for the differences between the means of pharmacokinetic parameters, area under the curve (ASC0-t and maximum plasma concentration (Cmax, was made for each study by meta-analysis. RESULTS: The interchangeability between the combinations of the three products with Hydrochlorothiazide was confirmed based on the obtained confidence intervals. For the drugs studied with Enalapril Maleate interchangeability has not been confirmed for 50% of the product comparisons. CONCLUSION: The exchange was established between the three products with hydrochlorothiazide. However, for the Enalapril Maleate half of the products studied are not interchangeable, considering they do not match the established intervals for bioequivalence tests, so the pharmacokinetics behavior and thus the effectiveness of the product may be changed.

  18. TMACS test procedure TP001: Alarm management. Revision 6

    International Nuclear Information System (INIS)

    Scanlan, P.K.

    1994-01-01

    The TMACS Software Project Test Procedures translate the project's acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure addresses the Alarm Management requirements of the TMACS. The features to be tested are: real-time alarming on high and low level and discrete alarms, equipment alarms, dead-band filtering, alarm display color coding, alarm acknowledgement, and alarm logging

  19. TMACS test procedure TP003: Graphics. Revision 5

    International Nuclear Information System (INIS)

    Scanlan, P.K.

    1994-01-01

    The TMACS Software Project Test Procedures translate the project's acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure addresses the graphics requirements of the TMACS. The features to be tested are the data display graphics and the graphic elements that provide for operator control and selection of displays

  20. TMACS test procedure TP003: Graphics. Revision 6

    International Nuclear Information System (INIS)

    Scanlan, P.K.; Washburn, S.

    1994-01-01

    The TMACS Software Project Test Procedures translate the project's acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure addresses the graphics requirements of the TMACS. The features to be tested are the data display graphics and the graphic elements that provide for operator control and selection of displays

  1. TRUPACT-II procedures and maintenance instructions

    International Nuclear Information System (INIS)

    1994-01-01

    The purpose of this document is to provide the technical requirements for operation, inspection and maintenance of a TRUPACT-II Shipping Package and directly related components. This document shall supply the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP) and Certificate of Compliance (C of C) 9218. In the event there is a conflict between this document and the TRUPACT-II SARP (NRC Certificate of Compliance No. 9218), the TRUPACT-II SARP shall govern. This document details the operations, maintenance, repair, replacement of components, as well as the documentation required and the procedures to be followed to maintain the integrity of the TRUPACT-II container. These procedures may be modified for site use, but as a minimum all parameters and format listed herein must be included in any site modified version. For convenience and where applicable steps may be performed out of sequence. Packaging and payload handling equipment and transport trailers have been specifically designed for use with the TRUPACT-II Packaging. This document discusses the minimum required procedures for use of the adjustable center of gravity lift fixture and the TRUPACT-II transport trailer in conjunction with the TRUPACT-II Packaging

  2. SOFI, a symptom-oriented, fully integrated emergency operating procedure

    International Nuclear Information System (INIS)

    Knobel, R.C.

    1987-01-01

    This paper builds on a previous look at decision-tree emergency operating procedures to describe the symptom-oriented fully integrated (SOFI) process and what has been accomplished. The SOFI emergency operating procedures process results in one emergency operation procedure, thus eliminating the confusion and resultant jumping into and out of the wrong procedure (or the right ones if the operator misdiagnoses the event combination). The SOFI process results in emergency operating procedures that have a simple single-entry condition. The SOFI process results in emergency operating procedures that, once entered, require the operator to, by evaluating symptoms, determine the state of the plant and then provide the operator with the steps necessary to put the plant into a safer state. The full paper describes how, by the SOFI process, the typical boiling water reactor (BWR) plant, pre-TMI emergency procedures inventory (in some cases, abnormal procedures are included) is broken down to provide the steps to be integrated with the BWR Owners Group Emergency Procedures Guidelines into the SOFI emergency operating procedures. In summary, the paper provides a point-by-point comparison of the SOFI emergency operating procedures solution to the procedural problems identified in the post-TMI reviews

  3. Learning procedures from interactive natural language instructions

    Science.gov (United States)

    Huffman, Scott B.; Laird, John E.

    1994-01-01

    Despite its ubiquity in human learning, very little work has been done in artificial intelligence on agents that learn from interactive natural language instructions. In this paper, the problem of learning procedures from interactive, situated instruction is examined in which the student is attempting to perform tasks within the instructional domain, and asks for instruction when it is needed. Presented is Instructo-Soar, a system that behaves and learns in response to interactive natural language instructions. Instructo-Soar learns completely new procedures from sequences of instruction, and also learns how to extend its knowledge of previously known procedures to new situations. These learning tasks require both inductive and analytic learning. Instructo-Soar exhibits a multiple execution learning process in which initial learning has a rote, episodic flavor, and later executions allow the initially learned knowledge to be generalized properly.

  4. Preschooler test or procedure preparation

    Science.gov (United States)

    ... your child during and after the procedure with books, songs, counting, deep breathing, or blowing bubbles. PLAY ... can be present during the procedure. Ask if anesthesia can be used to reduce your child's discomfort. ...

  5. Toddler test or procedure preparation

    Science.gov (United States)

    ... use after the procedure. Distract your child with books, songs, or a simple activity such as blowing ... can be present during the procedure. Ask if anesthesia can be used, if appropriate, to reduce your ...

  6. Optimal data verification procedures

    International Nuclear Information System (INIS)

    Avenhaus, R.; Busse, S.; Piehlmeier, G.

    1991-01-01

    In order to verify the material balance data reported by plant operators, the safeguards authority performs independent measurements on a random sampling basis and compares the resulting data with the reported ones. It is shown that the so-called D-statistic, which originally has been justified with heuristic arguments and since then has been used in practice for many years, is optimal if the total assumed falsification is small. Furthermore, numerical calculations indicate that for larger total falsification, where a more complicated test procedure would be optimal, the D-test is still useful from a practical point of view. For very large total falsification, the optimal test statistic is complicated; this, however, is not so important since here one is approaching the attribute sampling area

  7. 47 CFR 80.310 - Watch required by voluntary vessels.

    Science.gov (United States)

    2010-10-01

    ... Section 80.310 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Safety Watch Requirements and Procedures Ship Station Safety...] Distress, Alarm, Urgency and Safety Procedures ...

  8. Space Geodesy Project Information and Configuration Management Procedure

    Science.gov (United States)

    Merkowitz, Stephen M.

    2016-01-01

    This plan defines the Space Geodesy Project (SGP) policies, procedures, and requirements for Information and Configuration Management (CM). This procedure describes a process that is intended to ensure that all proposed and approved technical and programmatic baselines and changes to the SGP hardware, software, support systems, and equipment are documented.

  9. Logistic Costs of Privileged Procedures in the Republic of Croatia

    Directory of Open Access Journals (Sweden)

    Čedomir Ivaković

    2006-07-01

    Full Text Available Logistic processes condition more and more the rationalizationof time required for manipulation of goods (loading,unloading, storage. The customs representation costs that arethe result of loss of time due to the customs procedures exclusivelyduring the working hours of the customs office affect alsothe total logistic costs, and may be significantly reduced by applyingthe privileged procedures in import and export.

  10. Procedural City Layout Generation Based on Urban Land Use Models

    NARCIS (Netherlands)

    Groenewegen, S.A.; Smelik, R.M.; Kraker, J.K. de; Bidarra, R.

    2009-01-01

    Training and simulation applications in virtual worlds require significant amounts of urban environments. Procedural generation is an efficient way to create such models. Existing approaches for procedural modelling of cities aim at facilitating the work of urban planners and artists, but either

  11. 47 CFR 101.103 - Frequency coordination procedures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Frequency coordination procedures. 101.103... SERVICES FIXED MICROWAVE SERVICES Technical Standards § 101.103 Frequency coordination procedures. (a..., LMDS licensees shall be subject to the protection requirement established in this section in the case...

  12. 28 CFR 80.12 - Accounting requirements.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Accounting requirements. 80.12 Section 80... PROCEDURE § 80.12 Accounting requirements. Neither the submission of a request for an FCPA Opinion, its... comply with the accounting requirements of 15 U.S.C. 78m(b)(2) and (3). ...

  13. 49 CFR 383.111 - Required knowledge.

    Science.gov (United States)

    2010-10-01

    ... importance of proper visual search, and proper visual search methods. (6) Communication. The principles and procedures for proper communications and the hazards of failure to signal properly. (7) Speed management. The... STANDARDS; REQUIREMENTS AND PENALTIES Required Knowledge and Skills § 383.111 Required knowledge. All...

  14. 40 CFR 86.1823-08 - Durability demonstration procedures for exhaust emissions.

    Science.gov (United States)

    2010-07-01

    ... control device. This procedure requires installation of the catalyst-plus-oxygen-sensor system on a... period of time calculated from the bench aging time (BAT) equation. The BAT equation requires, as input... procedure to future durability groups. The manufacturer may apply a durability procedure approved under...

  15. Quantization Procedures; Sistemas de cuantificacion

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera, J. A.; Martin, R.

    1976-07-01

    We present in this work a review of the conventional quantization procedure, the proposed by I.E. Segal and a new quantization procedure similar to this one for use in non linear problems. We apply this quantization procedures to different potentials and we obtain the appropriate equations of motion. It is shown that for the linear case the three procedures exposed are equivalent but for the non linear cases we obtain different equations of motion and different energy spectra. (Author) 16 refs.

  16. Vascular surgery training trends from 2001-2007: A substantial increase in total procedure volume is driven by escalating endovascular procedure volume and stable open procedure volume.

    Science.gov (United States)

    Schanzer, Andres; Steppacher, Robert; Eslami, Mohammad; Arous, Elias; Messina, Louis; Belkin, Michael

    2009-05-01

    Endovascular procedure volume has increased rapidly, and endovascular procedures have become the initial treatment option for many vascular diseases. Consequently, training in endovascular procedures has become an essential component of vascular surgery training. We hypothesized that, due to this paradigm shift, open surgical case volume may have declined, thereby jeopardizing training and technical skill acquisition in open procedures. Vascular surgery trainees are required to log both open and endovascular procedures with the Accreditation Council for Graduate Medical Education (ACGME). We analyzed the ACGME database (2001-2007), which records all cases (by Current Procedural Terminology [CPT] code) performed by graduating vascular trainees. Case volume was evaluated according to the mean number of cases performed per graduating trainee. The mean number of total major vascular procedures performed per trainee increased by 174% between 2001 and 2007 (from 298.3 to 519.2). Endovascular diagnostic and therapeutic procedures increased by 422% (from 63.7 to 269.1) and accounted for 93.0% of the increase in total procedures. The number of open aortic procedures (aneurysm, occlusive, mesenteric, renal) decreased by 17.1% (from 49.7 to 41.2), while the number of endovascular aortic aneurysm repair procedures increased by 298.8% (from 16.9 to 50.5). Specifically, open aortic aneurysm procedures decreased by 21.8%, aortobifemoral bypass increased by 3.2%, and open mesenteric or renal procedures decreased by 13%. Infrainguinal bypass procedures remained relatively constant (from 37.6 to 36.5, 2.9% decrease), and the number of carotid endarterectomy procedures performed did not change significantly (from 43.6 to 42.2, 3.2% decrease). Vascular surgery trainees are performing a vastly increased total number of procedures. This increase in total procedure volume is almost entirely attributable to the recent increase in endovascular procedures. Aside from a small decline in open

  17. Model of Procedure Usage – Results from a Qualitative Study to Inform Design of Computer-Based Procedures

    Energy Technology Data Exchange (ETDEWEB)

    Johanna H Oxstrand; Katya L Le Blanc

    2012-07-01

    The nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. As a step toward the goal of improving procedure use performance, researchers, together with the nuclear industry, have been looking at replacing the current paper-based procedures with computer-based procedure systems. The concept of computer-based procedures is not new by any means; however most research has focused on procedures used in the main control room. Procedures reviewed in these efforts are mainly emergency operating procedures and normal operating procedures. Based on lessons learned for these previous efforts we are now exploring a more unknown application for computer based procedures - field procedures, i.e. procedures used by nuclear equipment operators and maintenance technicians. The Idaho National Laboratory, the Institute for Energy Technology, and participants from the U.S. commercial nuclear industry are collaborating in an applied research effort with the objective of developing requirements and specifications for a computer-based procedure system to be used by field operators. The goal is to identify the types of human errors that can be mitigated by using computer-based procedures and how to best design the computer-based procedures to do this. The underlying philosophy in the research effort is “Stop – Start – Continue”, i.e. what features from the use of paper-based procedures should we not incorporate (Stop), what should we keep (Continue), and what new features or work processes should be added (Start). One step in identifying the Stop – Start – Continue was to conduct a baseline study where affordances related to the current usage of paper-based procedures were identified. The purpose of the study was to develop a model of paper based procedure use which will help to identify desirable features for computer based procedure prototypes. Affordances such as note taking, markups

  18. 47 CFR 11.61 - Tests of EAS procedures.

    Science.gov (United States)

    2010-10-01

    ... tests will conform with the procedures in the EAS Operating Handbook. (1) Required Monthly Tests of the..., activation must include transmission of the EAS header and EOM codes. Analog and digital television broadcast...

  19. Standardisation of heavy vehicle crash investigation procedures in South Africa

    CSIR Research Space (South Africa)

    Dube, S

    2015-07-01

    Full Text Available that contribute to a freight accident. Comprehensive road accident investigation procedures, will lead to the availability of reliable road accident data. This is crucial because effective road safety interventions require that contributory factors like road...

  20. 76 FR 19022 - Rules of Practice and Procedure

    Science.gov (United States)

    2011-04-06

    ... hardship, manifest injustice, or if the expeditious conduct of business so requires.'' 46 CFR 502.10. The Commission desires to ensure that procedures are consistent with modern practice while giving due regard to...

  1. 5 CFR 3301.102 - Procedure for accomplishing disqualification.

    Science.gov (United States)

    2010-01-01

    ... ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF ENERGY § 3301.102 Procedure for accomplishing...) Disqualification from matter effecting prospective employers. A DOE employee who is required, in accordance with 5...

  2. 32 CFR 204.3 - Policy and procedures.

    Science.gov (United States)

    2010-07-01

    ... immediate or substantial gain or values (which may or may not be measurable in monetary terms) than those... statutes or DoD issuances require different practices or procedures, such as for: (i) Morale, welfare, and...

  3. Simplified Civil Procedure in Japan

    NARCIS (Netherlands)

    E. Sugiyama (Etsuko)

    2015-01-01

    textabstractJapanese civil procedure covers four types of simplified procedures: ordinary proceedings in summary courts; actions on bills, notes, and checks; actions on small claims; and payment orders. Actions on small claims were newly introduced as civil procedure in 1996 to promote public access

  4. Procedural violation in the licensing procedure and possible legal consequences; Verfahrensmaengel im Konzessionierungsverfahren und etwaige Rechtsfolgen

    Energy Technology Data Exchange (ETDEWEB)

    Meyer-Hetling, Astrid; Probst, Matthias Ernst; Wolkenhauer, Soeren [Kanzlei Becker Buettner Held (BBH), Berlin (Germany)

    2012-07-15

    With respect to paragraph 46 sect. 2 to 4 EnWG (Energy Economy Law) communities are required to provide a publication procedure and competition procedure ('licensing procedure') for the new assignment of easement agreements for the establishment of local power supply systems and natural gas supply systems. The specific design of the selection process legally is regulated only rudimentary. Nevertheless old concessionaires increasingly deny the statutory grid transfer to the new concessionaires relying on supposed errors in the selection process. The unclear legal situation and the inconsistent, sometimes unreasonably strict jurisdiction and jurisprudence of antitrust as well as regulatory authorities resulted to a considerable legal certainty in communities and grid operators. Unless the legislature establishes the necessary legal clarity, the competent courts and authorities are invoked to act moderately in the examination of licensing procedures.

  5. Readability of Invasive Procedure Consent Forms.

    Science.gov (United States)

    Eltorai, Adam E M; Naqvi, Syed S; Ghanian, Soha; Eberson, Craig P; Weiss, Arnold-Peter C; Born, Christopher T; Daniels, Alan H

    2015-12-01

    Informed consent is a pillar of ethical medicine which requires patients to fully comprehend relevant issues including the risks, benefits, and alternatives of an intervention. Given the average reading skill of US adults is at the 8th grade level, the American Medical Association (AMA) and the National Institutes of Health (NIH) recommend patient information materials should not exceed a 6th grade reading level. We hypothesized that text provided in invasive procedure consent forms would exceed recommended readability guidelines for medical information. To test this hypothesis, we gathered procedure consent forms from all surgical inpatient hospitals in the state of Rhode Island. For each consent form, readability analysis was measured with the following measures: Flesch Reading Ease Formula, Flesch-Kincaid Grade Level, Fog Scale, SMOG Index, Coleman-Liau Index, Automated Readability Index, and Linsear Write Formula. These readability scores were used to calculate a composite Text Readability Consensus Grade Level. Invasive procedure consent forms were found to be written at an average of 15th grade level (i.e., third year of college), which is significantly higher than the average US adult reading level of 8th grade (p < 0.0001) and the AMA/NIH recommended readability guidelines for patient materials of 6th grade (p < 0.0001). Invasive procedure consent forms have readability levels which makes comprehension difficult or impossible for many patients. Efforts to improve the readability of procedural consent forms should improve patient understanding regarding their healthcare decisions. © 2015 Wiley Periodicals, Inc.

  6. PENILE ENHANCEMENT PROCEDURES: UROLOGICAL AND ETHICOLEGAL ISSUES

    Directory of Open Access Journals (Sweden)

    Marco Vella

    2012-04-01

    Full Text Available Phalloplasty procedures for most men requiring penile augmentation surgery are cosmetic procedures; generally the patients have a normal-sized and fully functional penis but they think that their penis is too small. There are not well defined indications for penile enhancement surgery and, except for the treatment of “micropenis”, there are not established guidelines and the outcome measures for success are still unclear. All penile enhancement techniques often do not reach the expected result and the grade of patient’s satisfaction is frequently poor. Phalloplasty procedures for psychological dysmorfism are not approved by any scientific society and the majority of these procedures are performed in private settings. The ethical and medicolegal problems resulting from a penis enhancement can be various and numerous, but few of them are reported in literature. After phalloplasty an attribution of professional responsibility and request of reimbursement is not rare. In this contribution the authors summarize a panorama of several urological and medico-legal aspects related to phalloplasty procedures.

  7. Complications with Outpatient Angiography and Interventional Procedures

    International Nuclear Information System (INIS)

    Young, Noel; Chi, Ka-Kit; Ajaka, Joe; McKay, Lesa; O'Neill, Diane; Wong, Kai Ping

    2002-01-01

    Purpose: To prospectively identify the complications, and rates of complication, in outpatient angiography and interventional procedures. Methods: There were 1050 consecutive patients, 646 men and 404 women, aged 17-89 years, with a total of 1239 procedures studied in a 2-year period, 1997 to 1999. Results: There were 560 cases of aorto-femoral angiography,resulting in 124 complications (22%), with pain or hematoma in 110.There were 206 cases of neck and cerebral angiography, resulting in 51 complications (25%), with pain and hematoma in 34, transient ischemic attack in 2 and cerebrovascular accident in 1. There were 197 interfentional procedures, with 177 being balloon dilatations, resulting in 68 complications (35%), with 2 having hematomas and 1 having hematoma/abscess requiring active treatment. There were 276 cases having various 'other' procedures (e.g., renal angiography),resulting in 65 complications (24%), with pain and hematoma in 61. No procedure-related death occurred. Eighteen cases (1.5%) had significant complications, with contrast allergy in eight. Conclusion: Outpatient angiography and intervention are relatively safe, with low significant complication rates

  8. [Choice of bariatric and metabolic surgical procedures].

    Science.gov (United States)

    Liang, Hui; Lin, Shibo; Guan, Wei

    2017-04-25

    Bariatric and metabolic surgery has become the clinical hot topic of the treatment of metabolic syndromes including obesity and diabetes mellitus, but how to choose the appropriate surgical procedure remains the difficult problem in clinical practice. Clinical guidelines of American Society for Metabolic and Bariatric Surgery(ASMBS)(version 2013) introduced the procedures of bariatric and metabolic surgery mainly including biliopancreatic diversion with duodenal switch(BPD-DS), laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy(LSG). To choose the appropriate bariatric and metabolic procedure, the surgeons should firstly understand the indications and the contraindications of each procedure. Procedure choice should also consider personal condition (body mass index, comorbidities and severity of diabetes), family and socioeconomic status (postoperative follow-up attendance, understanding of potential surgical risk of gastrectomy and patient's will), family and disease history (patients with high risk of gastric cancer should avoid LRYGB; patients with gastroesophageal reflux disease should avoid LSG) and associated personal factors of surgeons. With the practice of bariatric and metabolic surgery, the defects, especially long-term complications, of different procedures were found. For example, LRYGB resulted in higher incidence of postoperative anemia and marginal ulcer, high risk of gastric cancer as well as the requirement of vitamin supplementation and regular follow-up. Though LSG has lower surgical risk, its efficacy of diabetes mellitus remission and long-term weight loss are inferior to the LRYGB. These results pose challenges to the surgeons to balance the benefits and risks of the bariatric procedures. A lot of factors can affect the choice of bariatric and metabolic procedure. Surgeons should choose the procedure according to patient's condition with the consideration of the

  9. Development of transportation operations requirements

    International Nuclear Information System (INIS)

    Grady, S.T.; Best, R.E.; Danese, F.L.; Peterson, R.W.; Pope, R.B.

    1990-01-01

    Transport conditions at various utility sties vary dramatically in terms of characteristics at and near the site, requirements, administrative procedures, and other factors. Continuation of design efforts for the OCRWM transportation operations system requires that the operating requirements for the transportation system -- quantity of fuel per unit time per site -- be identified so that the effect the variations have on the system can be accommodated. The approach outlined in this paper provides for an identification of specific sites, evaluation of shipment capabilities at each site, and integration of the sites into multi-site shipping campaigns to scope the logistics management problem for the transportation operations system. 1 fig., 1 tab

  10. 47 CFR 80.100 - Morse code requirement.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Morse code requirement. 80.100 Section 80.100... MARITIME SERVICES Operating Requirements and Procedures Operating Procedures-General § 80.100 Morse code requirement. The code employed for telegraphy must be the Morse code specified in the Telegraph Regulations...

  11. Transgenesis procedures in Xenopus

    Science.gov (United States)

    Chesneau, Albert; Sachs, Laurent M.; Chai, Norin; Chen, Yonglong; Pasquier, Louis Du; Loeber, Jana; Pollet, Nicolas; Reilly, Michael; Weeks, Daniel L.; Bronchain, Odile J.

    2010-01-01

    Stable integration of foreign DNA into the frog genome has been the purpose of several studies aimed at generating transgenic animals or producing mutations of endogenous genes. Inserting DNA into a host genome can be achieved in a number of ways. In Xenopus, different strategies have been developed which exhibit specific molecular and technical features. Although several of these technologies were also applied in various model organizms, the attributes of each method have rarely been experimentally compared. Investigators are thus confronted with a difficult choice to discriminate which method would be best suited for their applications. To gain better understanding, a transgenesis workshop was organized by the X-omics consortium. Three procedures were assessed side-by-side, and the results obtained are used to illustrate this review. In addition, a number of reagents and tools have been set up for the purpose of gene expression and functional gene analyses. This not only improves the status of Xenopus as a powerful model for developmental studies, but also renders it suitable for sophisticated genetic approaches. Twenty years after the first reported transgenic Xenopus, we review the state of the art of transgenic research, focusing on the new perspectives in performing genetic studies in this species. PMID:18699776

  12. Computer software review procedures

    International Nuclear Information System (INIS)

    Mauck, J.L.

    1993-01-01

    This article reviews the procedures which are used to review software written for computer based instrumentation and control functions in nuclear facilities. The utilization of computer based control systems is becoming much more prevalent in such installations, in addition to being retrofit into existing systems. Currently, the Nuclear Regulatory System uses Regulatory Guide 1.152, open-quotes Criteria for Programmable Digital Computer System Software in Safety-Related Systems of Nuclear Power Plantsclose quotes and ANSI/IEEE-ANS-7-4.3.2-1982, open-quotes Application Criteria for Programmable Digital Computer Systems in Safety Systems of Nuclear Power Generating Stationsclose quotes for guidance when performing reviews of digital systems. There is great concern about the process of verification and validation of these codes, so when inspections are done of such systems, inspectors examine very closely the processes which were followed in developing the codes, the errors which were detected, how they were found, and the analysis which went into tracing down the causes behind the errors to insure such errors were not propagated again in the future

  13. NASA trend analysis procedures

    Science.gov (United States)

    1993-01-01

    This publication is primarily intended for use by NASA personnel engaged in managing or implementing trend analysis programs. 'Trend analysis' refers to the observation of current activity in the context of the past in order to infer the expected level of future activity. NASA trend analysis was divided into 5 categories: problem, performance, supportability, programmatic, and reliability. Problem trend analysis uncovers multiple occurrences of historical hardware or software problems or failures in order to focus future corrective action. Performance trend analysis observes changing levels of real-time or historical flight vehicle performance parameters such as temperatures, pressures, and flow rates as compared to specification or 'safe' limits. Supportability trend analysis assesses the adequacy of the spaceflight logistics system; example indicators are repair-turn-around time and parts stockage levels. Programmatic trend analysis uses quantitative indicators to evaluate the 'health' of NASA programs of all types. Finally, reliability trend analysis attempts to evaluate the growth of system reliability based on a decreasing rate of occurrence of hardware problems over time. Procedures for conducting all five types of trend analysis are provided in this publication, prepared through the joint efforts of the NASA Trend Analysis Working Group.

  14. 78 FR 79408 - Agency Information Collection Activities; Notice of Intent To Renew Collection: Procedural...

    Science.gov (United States)

    2013-12-30

    ... COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities; Notice of Intent To Renew Collection: Procedural Requirements for Requests for Interpretative, No-Action, and Exemptive... the proposed collection of information listed below. Abstract: This collection covers the procedural...

  15. 47 CFR 80.319 - Radiotelegraph distress call and message transmission procedure.

    Science.gov (United States)

    2010-10-01

    ...) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Safety Watch Requirements and Procedures Distress, Alarm, Urgency and Safety Procedures § 80.319 Radiotelegraph distress call and message...

  16. 47 CFR 80.320 - Radiotelephone distress call and message transmission procedure.

    Science.gov (United States)

    2010-10-01

    ...) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Safety Watch Requirements and Procedures Distress, Alarm, Urgency and Safety Procedures § 80.320 Radiotelephone distress call and message...

  17. 20 CFR 656.18 - Optional special recruitment and documentation procedures for college and university teachers.

    Science.gov (United States)

    2010-04-01

    ... documentation procedures for college and university teachers. 656.18 Section 656.18 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR LABOR CERTIFICATION PROCESS FOR PERMANENT... and documentation procedures for college and university teachers. (a) Filing requirements...

  18. Human factors research plan for instrument procedures : FY12 version 1.1

    Science.gov (United States)

    2012-06-19

    This research will support the development of instrument procedures for performance-based navigation (PBN) operations. These procedures include, but are not limited to, area navigation (RNAV) and required navigation performance (RNP) operations. The ...

  19. Predictors for secondary procedures in walking DDH.

    Science.gov (United States)

    Gholve, Purushottam A; Flynn, John M; Garner, Matthew R; Millis, Michael B; Kim, Young-Jo

    2012-01-01

    Persistent or recurrent hip dysplasia and/or loss of reduction can complicate the treatment of developmental dysplasia of the hip (DDH) in walking children. In this study, we identify predictors for secondary procedures after open reduction of the hip in walking children with DDH. We performed a retrospective study of walking children with idiopathic DDH treated with open reduction of the hip and followed up for >5 years. Perioperative factors were analyzed to investigate predictors of reoperation. Factors associated with the need for secondary procedures were identified. Acetabular remodeling was analyzed with a graphical plot of serial (0, 6 and 12 mo, and yearly) mean acetabular index and SD. There were 49 open reductions of the hip in 42 patients (34 female, 8 male) at a mean age of 31.3 months (range, 15.3 to 92.6 mo), with a mean follow-up of 9.7 years (5 to 16.9 y). Twelve (24%) patients had open reduction only, 15 (31%) had concurrent pelvic osteotomy, 4 (8%) had femoral osteotomy, and 18 (37%) had both femoral and pelvic osteotomy. Four (8%) patients required repeat open reduction at a mean of 5.1 months (range, 4 to 7.5 mo) after index surgery. Twenty-four (49%) patients had at least 1 secondary surgery for dysplasia at a mean of 3.2 years after index surgery. Six of the 24 (25%) had 2 and 2/24 (8.3%) had 3 additional operations. Of the 27 patients who did not have concurrent femoral osteotomy at index surgery, 19/27 (73%) required a secondary procedure; this significantly predicted the need for reoperation (P<0.001). Only 5/22 patients with femoral osteotomy at index surgery required a secondary procedure. Maximum acetabular remodeling was observed in the first 4 years after primary reduction, and the mean acetabular index remodeled from 43.9 to 20.3 degrees during this period. Forty-nine percent of the patients in this cohort required secondary procedures to treat hip dysplasia. Open reduction without concurrent femoral osteotomy strongly predicted the

  20. Inservice inspection procedures and training according to the ASME code

    International Nuclear Information System (INIS)

    Greenwald, S.M.; Chockie, L.J.

    1987-01-01

    Mandatory training of the technical staff at a nuclear power plant is of paramount importance if we are to avoid costly plant shutdowns. This training should include the requirements for both Preservice and Inservice Inspection, in addition to Quality Assurance procedures as required by the American Society of Mechanical Engineers (ASME) Code. The training is best accomplished by utilizing instructors who are thoroughly familiar with plant operations and the ASME Code, as well as serving on one of the Code committees. This paper focuses on the Inservice Inspection procedures and the results of an intensive training effort to implement such procedures. (author)

  1. Inservice inspection procedures and training according to the ASME code

    Energy Technology Data Exchange (ETDEWEB)

    Greenwald, S.M.; Chockie, L.J.

    1988-01-01

    Mandatory training of the technical staff at a nuclear power plant is of paramount importance if we are to avoid costly plant shutdowns. This training should include the requirements for both Preservice and inservice Inspection, in addition to Quality Assurance procedures as required by the American Society of Mechanical Engineers (ASME) Code. The training is best accomplished by utilizing instructors who are thoroughly familiar with plant operations and the ASME Code, as well as serving on one of the code committees. This paper focuses on the Inservice Inspection procedures and the results of an intensive training effort to implement such procedures.

  2. Software quality assurance procedures for radioactive waste risk assessment codes

    International Nuclear Information System (INIS)

    Hill, I.; Mayer, J.

    1990-01-01

    This support study for the evaluation of the safety of geological disposal systems is aimed at identifying the requirements for software quality assurance procedures for radioactive waste risk assessment codes, and to recommend appropriate procedures. The research covers: (i) the analysis of existing procedures and definition of requirements; (ii) a case study of the use of some existing procedures; (iii) the definition and the implementation of procedures. The report is supported by appendices that give more detail on the procedures recommended. It is intended to provide ideas on the steps that should be taken to ensure the quality of the programs used for assessment of the safety case for radioactive waste repositories, and does not represent the introduction of wholly new ideas or techniques. The emphasis throughout is on procedures that will be easily implemented, rather than on the fully rigorous procedures that are required for some application areas. The study has concentrated on measures that will increase the confidence in repository performance assessments among the wider scientific/engineering community, and the lay public

  3. Automated development, control, and maintenance of plant procedures

    International Nuclear Information System (INIS)

    Gilbert, L.A.

    1990-01-01

    Plants create and track thousands of documents and written procedures every year. Increasing regulations and document requirements demand more and more resources. Not only must the procedures that are written be detailed and technically accurate, they must be controlled and revised to keep pace with changing regulations, procedure requirements and equipment. The basis of this paper is the introduction of a network-based automated approach to developing, tracking, controlling, storing, and revising procedures. This network-based product, referred to herein as PRONET, combines the best of work processing, relational data base management, graphics, and project managements software to provide the capabilities needed to effectively and efficiently automate the development, control, and maintenance of plant procedures

  4. AGREED-UPON PROCEDURES, PROCEDURES FOR AUDITING EUROPEAN GRANTS

    Directory of Open Access Journals (Sweden)

    Daniel Petru VARTEIU

    2016-12-01

    The audit of EU-funded projects is an audit based on agreed-upon procedures, which are established by the Managing Authority or the Intermediate Body. Agreed-upon procedures can be defined as engagements made in accordance with ISRS 4400, applicable to agreed-upon procedures, where the auditor undertakes to carry out the agreed-upon procedures and issue a report on factual findings. The report provided by the auditor does not express any assurance. It allows users to form their own opinions about the conformity of the expenses with the project budget as well as the eligibility of the expenses.

  5. A manual of nuclear medicine procedures

    International Nuclear Information System (INIS)

    Das, B.K.; Noreen Norfaraheen Lee Abdullah

    2012-01-01

    Nuclear medicine is a fast growing specialty. The procedures provide quantitative parameters of organ functions required for modern practice of medicine. With the development of new machines and increased application of computer software, the procedures are under continuous change. Some procedures have become outdated or redundant while new methods have been introduced to enhance the quality of information obtained from a particular application. Although there are a few books published abroad to inform doctors and technical staff about the procedures, a comprehensive source to give quick information about how different test are performed, particularly the new developments and the expected outcome both in normal and abnormal cases has been a long felt need. The physician ordering a Nuclear Medicine test also needs to know what patient preparations are required for optimal results, how to satisfy the queries of the patient particularly in respect of radiation exposure which sometimes can be a major concern of the patient. This manual has been prepared not only to describe technical details of various procedures that are currently practiced in Nuclear Medicine, but also to provide quick information for the doctors and health care personnel on how to inform the patients about the investigation for which they are being referred and how to interpret the results. Since there is no such comprehensive book published yet in Asia including South-East Asia, it is likely to be in great demand in the region. All students of Master Degree, M.D., DRM, DMRIT, M.Sc. (Nuclear Medicine) and technologists already working in various diagnostic centers will likely buy this book. General practitioners and specialists who refer patients for different radioisotope investigations may find this book useful for quick reference. (author)

  6. Regularization mechanism in blind tip reconstruction procedure

    International Nuclear Information System (INIS)

    Jóźwiak, G.; Henrykowski, A.; Masalska, A.; Gotszalk, T.

    2012-01-01

    In quantitative investigations of mechanical and chemical surface parameters using atomic force microscopy (AFM) techniques the determination of the probe radius and shape is required. To the most favorable methods of the microprobe characterization belongs the blind tip reconstruction method (BTR). The BTR similar to many other inverse problems is sensitive to noise and needs the so-called regularization mechanism. In this article we describe and investigate two the most popular regularization schemes, which were proposed in Villarubia et al. (1997) and Tian et al. (2008) . We have shown that the procedure described in Tian et al. (2008) enables very effective probe shape reconstruction if we know the statistics of noise present in the AFM system. The increase of effectiveness with relation to the procedure described in Villarubia (1997) is so significant that makes it possible to reconstruct probes with much larger resolution. We have also noticed the fact, that probes reconstructed by means of the procedure presented in Tian et al. (2008) have flat apexes for AFM images with low signal to noise ratio (SNR). We propose procedure, which can improve the probe apex reconstruction. It uses the AFM image to estimate the initial shape of the reconstructed probe. This shape may be further improved by the BTR algorithm. We have shown that it is possible only for the procedure described in Tian et al. (2008) . -- Highlights: ► We study regularization mechanism of blind tip reconstruction. ► We propose combination of direct probe imaging with BTR to improve the reconstruction of a probe apex. ► The possibility of improving efficiency of the BTR procedure is presented. ► The possibility of improving resolution of a reconstructed probe is presented.

  7. Pregnancy outcomes in female physicians in procedural versus non-procedural specialties.

    Science.gov (United States)

    Scully, Rebecca E; Stagg, Amy R; Melnitchouk, Nelya; Davids, Jennifer S

    2017-10-01

    Procedural based medical specialties require a longer training period and more intensive physical demands. The impact of working in procedural versus nonprocedural fields on pregnancy outcomes is not well understood. Data from 1559 US attending female physician mothers was gathered via an anonymous, IRB-approved online survey. Of the cohort, 400 (25.7%) reported practicing in a procedural field. Women in procedural fields were slightly older at the time of their most recent pregnancy. Rates of assistive reproductive technology use (procedural: 20.2% vs nonprocedural: 23.3%, P = 0.2), missing work during pregnancy (28.2% vs 24.5%, P = 0.13), cesarean delivery rate (36.0% vs 34.5%, P = 0.61), and missed work due to preterm labor (12.3% vs 12.5%, P = 0.91) were similar between the two groups. Although proceduralists were more likely to delay pregnancy, women in procedural fields had comparable rates of reproductive assistance, cesarean delivery, and missed work due to pregnancy-related complications despite the perceived challenges facing this group. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Behavioral Implications of Shortlisting Procedures

    OpenAIRE

    Christopher J. Tyson

    2012-01-01

    We consider two-stage "shortlisting procedures" in which the menu of alternatives is first pruned by some process or criterion and then a binary relation is maximized. Given a particular first-stage process, our main result supplies a necessary and sufficient condition for choice data to be consistent with a procedure in the designated class. This result applies to any class of procedures with a certain lattice structure, including the cases of "consideration filters," "satisficing with salie...

  9. Acquisition Policy and Procedures Program

    National Research Council Canada - National Science Library

    2001-01-01

    This Instruction establishes policies, responsibilities, and procedures for the procurement of goods and services to include supplies, equipment, publications, furniture, and information technology...

  10. Electronic Procedures for Medical Operations

    Science.gov (United States)

    2015-01-01

    Electronic procedures are replacing text-based documents for recording the steps in performing medical operations aboard the International Space Station. S&K Aerospace, LLC, has developed a content-based electronic system-based on the Extensible Markup Language (XML) standard-that separates text from formatting standards and tags items contained in procedures so they can be recognized by other electronic systems. For example, to change a standard format, electronic procedures are changed in a single batch process, and the entire body of procedures will have the new format. Procedures can be quickly searched to determine which are affected by software and hardware changes. Similarly, procedures are easily shared with other electronic systems. The system also enables real-time data capture and automatic bookmarking of current procedure steps. In Phase II of the project, S&K Aerospace developed a Procedure Representation Language (PRL) and tools to support the creation and maintenance of electronic procedures for medical operations. The goal is to develop these tools in such a way that new advances can be inserted easily, leading to an eventual medical decision support system.

  11. Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S.

    Science.gov (United States)

    Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

    2014-01-01

    Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results. PMID:24732068

  12. Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S.

    Directory of Open Access Journals (Sweden)

    Sabrina Trows

    2014-04-01

    Full Text Available Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA and the European Medicines Agency (EMA have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD, plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

  13. Pollutant Assessments Group procedures manual: Volume 2, Technical procedures

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    This is volume 2 of the manuals that describes the technical procedures currently in use by the Pollution Assessments Group. This manual incorporates new developments in hazardous waste assessment technology and administrative policy. Descriptions of the equipment, procedures and operations of such things as radiation detection, soil sampling, radionuclide monitoring, and equipment decontamination are included in this manual. (MB)

  14. Assessment of LANL transportation policies and procedures

    International Nuclear Information System (INIS)

    Danna, J.G.; Jennrich, E.A.; Lund, D.M.; Davis, K.D.; Hoevemeyer, S.S.

    1991-04-01

    In order to determine whether activities related to the transportation of waste at Los Alamos National Laboratory (LANL) were being conducted in accordance with DOE policy, requirements stated in applicable DOE Orders were reviewed and compared with LANL policies and procedures described in the Administrative Requirements and the On-Site Transportation Manual. The following DOE Orders were determined to pertain to waste transportation and thus reviewed to identify requirements for which LANL is responsible for satisfying: Order 5820.2A Radioactive Waste Management; Order 1540.1 Materials Transportation and Traffic Management; and Order 5480.3 Safety Requirements for the Packaging and Transportation of Hazardous Materials, Hazardous Substances, and Hazardous Wastes. The LANL On-Site Transportation Manual and the Administrative Requirements contained in the LANL Environment, Safety, and Health Manual were reviewed to verify that each of the requirements identified through the review of the Orders and 10 CFR Part 71 were being satisfied. The following Administrative Requirements were considered in this task: Shipment of Radioactive Materials; Radioactive Liquid Waste; Low-Level Radioactive Solid Waste; Chemical, Hazardous, and Mixed Waste; Polychlorinated Biphenyls; and Transuranic (TRU) Solid Waste

  15. 48 CFR 45.202 - Evaluation procedures.

    Science.gov (United States)

    2010-10-01

    ... offeror's property management plans, methods, practices, or procedures for accounting for property are... MANAGEMENT GOVERNMENT PROPERTY Solicitation and Evaluation Procedures 45.202 Evaluation procedures. (a) The...

  16. Procedures for evaluating technical specifications (PETS)

    International Nuclear Information System (INIS)

    Samanta, P.K.; Boccio, J.L.; Vesely, W.E.

    1987-01-01

    In this paper, aspects of technical specifications relating to Generic Issues B-56 and B-61 are discussed from a risk-standpoint. These primarily deal with the risk issues associated with (1) adaptive diesel test requirements/surveillance test intervals, and (2) the effectiveness of cumulative outage time requirements for controlling downtime risk. Risk and reliability approaches are presented which (1) allow risk-acceptable test intervals to be determined for any diesel and (2) show the potential risk-control capability of prescribed allowed cumulative outage times. This work was conducted through NRC's Procedures for Evaluating Technical Specifications (PETS) Program. The overall objective of this program is to develop and demonstrate methodologies that utilize risk insights and reliability techniques for evaluating the scope, detailed requirements, and safety impact of plant technical specifications

  17. Automation of procedure writing for the RLWTF

    International Nuclear Information System (INIS)

    Farnham, M.; MacDonald, A.

    1998-01-01

    In August of 1997, the Radioactive Liquid Waste Treatment Facility (RLWTF) at Los Alamos National Laboratory (LANL) recognized the need to re-engineer document management business process. All nuclear facilities at LANL are required to ensure that both the latest approved revision of controlled documents and any changes to those documents are available to operating personnel at all times. The Nuclear Materials Technology (NMT) Division was also re-engineering its document management business processes and searching for a solution. Both groups contacted several internal and external organizations in search of potential software solutions in use that would meet requirements. This report describes the objectives and features required by the software package, the choice of Procedure Design as the software package, and its implementation

  18. Surgical Procedures Needed to Eradicate Infection in Knee Septic Arthritis.

    Science.gov (United States)

    Dave, Omkar H; Patel, Karan A; Andersen, Clark R; Carmichael, Kelly D

    2016-01-01

    Septic arthritis of the knee is encountered on a regular basis by orthopedists and nonorthopedists. No established therapeutic algorithm exists for septic arthritis of the knee, and there is much variability in management. This study assessed the number of surgical procedures, arthroscopic or open, required to eradicate infection. The study was a retrospective analysis of 79 patients who were treated for septic knee arthritis from 1995 to 2011. Patients who were included in the study had native septic knee arthritis that had resolved with treatment consisting of irrigation and debridement, either open or arthroscopic. Logistic regression analysis was used to explore the relation between the interval between onset of symptoms and index surgery and the use of arthroscopy and the need for multiple procedures. Fifty-two patients met the inclusion criteria, and 53% were male, with average follow-up of 7.2 years (range, 1-16.2 years). Arthroscopic irrigation and debridement was performed in 70% of cases. On average, successful treatment required 1.3 procedures (SD, 0.6; range, 1-4 procedures). A significant relation (P=.012) was found between time from presentation to surgery and the need for multiple procedures. With arthroscopic irrigation and debridement, most patients with septic knee arthritis require only 1 surgical procedure to eradicate infection. The need for multiple procedures increases with time from onset of symptoms to surgery. Copyright 2016, SLACK Incorporated.

  19. Failure to Follow Written Procedures

    Science.gov (United States)

    2017-12-01

    Most tasks in aviation have a mandated written procedure to be followed specifically under the Code of Federal Regulations (CFR) Part 14, Section 43.13(a). However, the incidence of Failure to Follow Procedure (FFP) events continues to be a major iss...

  20. Proof Rules for Recursive Procedures

    NARCIS (Netherlands)

    Hesselink, Wim H.

    1993-01-01

    Four proof rules for recursive procedures in a Pascal-like language are presented. The main rule deals with total correctness and is based on results of Gries and Martin. The rule is easier to apply than Martin's. It is introduced as an extension of a specification format for Pascal-procedures, with

  1. Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats Estudo da bioequivalência de quatro diferentes marcas comerciais de maleato de enalapril em ratos espontaneamente hipertensos

    Directory of Open Access Journals (Sweden)

    Nilo César do Vale Baracho

    2008-04-01

    Full Text Available INTRODUCTION: High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. PURPOSE: To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR. METHODS: Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. RESULTS: The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. CONCLUSION: The use of generic drug and similars (A and B drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.INTRODUÇÃO: A hipertensão arterial é uma doença sistêmica que traz grandes repercussões clínicas e psico-sociais, cursa com uma elevada morbi-mortalidade e gera elevados gastos para o sistema de saúde. Seu tratamento envolve a utilização de fármacos anti-hipertensivos, os quais são comercializados como remédios de marca, genéricos ou similares. PURPOSE: Verificar o efeito anti-hipertensivo produzido por dose igualitária de diferentes marcas de maleato de enalapril, em ratos naturalmente hipertensos. MÉTODOS: Foram administrados, por meio de gavagem, 15 mg/kg de maleato de enalapril em 50 ratos naturalmente hipertensos e verificada a pressão arterial, através de pletismografia de cauda, a cada três dias, em um período de 16 dias. RESULTADOS

  2. Sepsis and multiorgan failure following TVT procedure.

    Science.gov (United States)

    Stec, Piotr; Connell, Rowan

    2014-04-01

    Tension-free vaginal tape (TVT), is a commonly performed, low risk procedure for treatment of stress urinary incontinence (SUI). Severe complications are rare, but can be potentially life threatening. We present a case of 66 year old patient who sustained bladder perforation at the time of TVT procedure and subsequently developed sepsis rapidly leading to multi-organ failure and triggering sequence of serious complications. During her inpatient stay she required ITU admission, emergency laparotomy, TVT mesh removal, bowel resection due to ischemic colitis and anticoagulation for pulmonary embolism. Despite of clinical picture of sepsis her microbiology tests were almost consistently negative. This case emphasise importance of awareness and quick recognition of TVT related complications. Patient ultimately survived and recovered thanks to timely and coordinated management by the multidisciplinary team of doctors.

  3. Alignment procedures for the CMS silicon tracker

    CERN Document Server

    Behr, Joerg

    2012-01-01

    The CMS all-silicon tracker consists of 16588 modules. Therefore its alignment procedures require sophisticated algorithms. Advanced tools of computing, tracking and data analysis have been deployed for reaching the targeted performance. Ultimate local precision is now achieved by the determination of sensor curvatures, challenging the algorithms to determine about 200k parameters simultaneously. Systematic biases in the geometry are controlled by adding further information into the alignment workflow, e.g. the mass of decaying resonances. The orientation of the tracker with respect to the magnetic field of CMS is determined with a stand-alone chi-square minimization procedure. The geometries are finally carefully validated. The monitored quantities include the basic track quantities for tracks from both collisions and cosmic muons and physics observables.

  4. Standardized procedure for tsunami PRA by AESJ

    International Nuclear Information System (INIS)

    Kirimoto, Yukihiro; Yamaguchi, Akira; Ebisawa, Katsumi

    2013-01-01

    After Fukushima Accident (March 11, 2011), the Atomic Energy Society of Japan (AESJ) started to develop the standard of Tsunami Probabilistic Risk Assessment (PRA) for nuclear power plants in May 2011. As Japan is one of the countries with frequent earthquakes, a great deal of efforts has been made in the field of seismic research since the early stage. To our regret, the PRA procedures guide for tsunami has not yet been developed although the importance is held in mind of the PRA community. Accordingly, AESJ established a standard to specify the standardized procedure for tsunami PRA considering the results of investigation into the concept, the requirements that should have and the concrete methods regarding tsunami PRA referring the opinions of experts in the associated fields in December 2011 (AESJ-SC-RK004:2011). (author)

  5. Thoracoscopy, a study of 129 procedures

    Directory of Open Access Journals (Sweden)

    Aleš Rozman

    2011-08-01

    Results: 78 (62.4 % of patients had malignant infiltration of the pleura and 47 (37.6 % had a benign pleural disease. The diagnostic accuracy of thoracoscopy was 91.5 %. The sensitivity in the diagnostics of malignant pleural disease was 86.1 %, the negative predictive value was 82.0 %. Talc pleurodesis was performed in 14 patients with malignant pleural infiltration. Complications were detected in 33 (26.4 % patients, most of them were not severe. Severe complications, such as empyema, bronchopleural fistula, prolonged duration of drainage, perforation of the diaphragm and trapped lung, occurred in 8 (6.4 % patients. 30-day mortality rate after the procedure was 0 %. Conclusions: Thoracoscopy has a high diagnostic yield with an acceptably low rate of complications. Nevertheless, it is an invasive procedure, which requires careful indications, patient’s consent, best surgical technique and an accurate postoperative follow up.

  6. 21 CFR 821.25 - Device tracking system and content requirements: manufacturer requirements.

    Science.gov (United States)

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE TRACKING REQUIREMENTS Tracking... procedure for the collection, maintenance, and auditing of the data specified in paragraphs (a) and (b) of... recording system, and the file maintenance procedures system; and (3) A quality assurance program that...

  7. 14 CFR 121.433 - Training required.

    Science.gov (United States)

    2010-01-01

    ... procedures set forth in a certificate holder's approved low-altitude windshear flight training program when... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Training required. 121.433 Section 121.433..., FLAG, AND SUPPLEMENTAL OPERATIONS Crewmember Qualifications § 121.433 Training required. (a) Initial...

  8. 20 CFR 632.41 - Reporting requirements.

    Science.gov (United States)

    2010-04-01

    ... EMPLOYMENT AND TRAINING PROGRAMS Administrative Standards and Procedures § 632.41 Reporting requirements... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Reporting requirements. 632.41 Section 632.41... registered mail, financial and program reports. Accuracy of all reports must be verified by the chief...

  9. Bioequivalence evaluation of new microparticulate capsule and ...

    African Journals Online (AJOL)

    Lornoxicam is a short-acting non-steroidal anti- inflammatory drug (NSAID) which belongs to the oxicam group. It decreases prostaglandin production by reducing cyclo-oxygenase (COX) activity. It is successfully being used in clinical settings for alleviating the symptoms of rheumatoid arthritis, osteoarthritis, acute sciatica.

  10. 47 CFR 97.509 - Administering VE requirements.

    Science.gov (United States)

    2010-10-01

    ..., grandchildren, stepchildren, parents, grandparents, stepparents, brothers, sisters, stepbrothers, stepsisters... accommodate an examinee whose physical disabilities require a special examination procedure. The administering VEs may require a physician's certification indicating the nature of the disability before determining...

  11. RTOD-photo operations and procedures manual

    Energy Technology Data Exchange (ETDEWEB)

    1966-03-15

    This document presents a survey of the EG&G NRDS photographic operation in four major sections and includes the work scope, procedures, some technical backgrounding and operational information. Two sections, Instrumentation and Photo Systems, include the areas of direct responsibilities while a section on Film Handling and Coordination and a section covering special information, pertinent to the project, are included to adequately complete this survey. The photographic group is housed in two trailers within the control point area at NRDS and from these trailers provides photographic support at a number of locations. Four camera bunkers, three camera towers, a kinescope system, a microfilm system and remote camera controls comprise the facilities that the group maintains and operates outside these trailers. The work load includes major items such as: motion picture coverage of the nuclear rocket engine tests, data record microfilming, kinescope recording, and documentary coverage of the company related operational responsibilities. In addition, a number of minor photographic services are extended, when required. The nature of the work, because of its importance within the research and development efforts at NRDS, requires optimum quality and efficiency throughout. The many procedures outlined here have been designed to satisfy these requirements.

  12. Fingertip replantation using the subdermal pocket procedure.

    Science.gov (United States)

    Lin, Tsan-Shiun; Jeng, Seng-Feng; Chiang, Yuan-Cheng

    2004-01-01

    Restoration of finger length and function are the goals of replantation after fingertip amputation. Methods include microsurgical replantation and nonmicrosurgical replantation, such as composite graft techniques. To increase the survival rates for composite grafts, the subcutaneous pocket procedure has been used as a salvage procedure. The subdermal pocket procedure, which is a modification of the subcutaneous pocket procedure, was used for replantation of 17 fingertips in 16 consecutive patients. Eight fingertips experienced guillotine injuries and the other nine fingertips experienced crush injuries. Revascularization of one digital artery without available venous outflow was performed for six fingers, and composite graft techniques were used for the other 11 fingers. The success rate was 16 of 17 cases. The difference in success rates for guillotine versus crush injuries was statistically significant. Comparison of patients with arterial anastomoses and patients without arterial anastomoses also indicated a statistically significant difference. Thirteen fingertips survived completely. One finger, demonstrating complete loss and early termination of the pocketing procedure, was amputated on the eighth postoperative day. Two fingers were partially lost because of severe crushing injuries. One finger demonstrated partial loss of more than one quarter of the fingertip, which required secondary revision, because the patient was a heavy smoker. The pocketing period was 8 +/- 1 days (mean +/- SD, n = 6) for the fingers revascularized with one digital arterial anastomosis and 13.3 +/- 1.9 days (n = 10) for the fingers successfully replanted with composite graft techniques. The mean active range of motion of the interphalangeal joint of the three thumbs was 65 +/- 5 degrees, and that of the distal interphalangeal joint of the other 11 fingers was 51 +/- 11 degrees. The static two-point discrimination result was 6.4 +/- 1.0 mm (n = 14) after an average of 11 +/- 5 months

  13. Advanced Noise Abatement Procedures for a Supersonic Business Jet

    Science.gov (United States)

    Berton, Jeffrey J.; Jones, Scott M.; Seidel, Jonathan A.; Huff, Dennis L.

    2017-01-01

    Supersonic civil aircraft present a unique noise certification challenge. High specific thrust required for supersonic cruise results in high engine exhaust velocity and high levels of jet noise during takeoff. Aerodynamics of thin, low-aspect-ratio wings equipped with relatively simple flap systems deepen the challenge. Advanced noise abatement procedures have been proposed for supersonic aircraft. These procedures promise to reduce airport noise, but they may require departures from normal reference procedures defined in noise regulations. The subject of this report is a takeoff performance and noise assessment of a notional supersonic business jet. Analytical models of an airframe and a supersonic engine derived from a contemporary subsonic turbofan core are developed. These models are used to predict takeoff trajectories and noise. Results indicate advanced noise abatement takeoff procedures are helpful in reducing noise along lateral sidelines.

  14. Geotechnical survey procedures for a repository mine

    International Nuclear Information System (INIS)

    Walther, C.

    1993-01-01

    The approach to the survey involves the operational realisation of an information process beginning with the definition of the survey programme and ending with the presentation of the survey results in the form of planning and assessment documents. - The survey methods must conform with the mine regulations, provide reliable predictions and produce the maximum possible salient information. The recording of large and varied amounts of data, and the complex interpretation procedures that follow require effective data and information management to allow the presentation of the results in accordance with the planning specifications. (orig.) [de

  15. Procedural Content Generation: Concepts and Related Works

    Directory of Open Access Journals (Sweden)

    MARIÑO, J. R. H.

    2016-12-01

    Full Text Available The digital games market is growing every year and game development is becoming increasingly complex. Thus, scalability in content generation may require the work of a team with hundreds of people. Procedural Content Generation (PCG comes as an alternative to decrease costs and accelerate the process of game production by creating content automatically or semi-automatically. This article presents some concepts and reviews works developed in PCG, aiming to provide a starting point for those interested in learning and going deeper in the subject of PCG for digital games.

  16. Imaging procedures in spinal infectious diseases

    International Nuclear Information System (INIS)

    Rodiek, S.O.

    2001-01-01

    A targeted successful treatment of spinal infectious diseases requires clinical and laboratory data that are completed by the contribution of imaging procedures. Neuroimaging only provides essential informations on the correct topography, localisation, acuity and differential diagnosis of spinal infectious lesions. MRI with its sensitivity concerning soft tissue lesions is a useful tool in detecting infectious alterations of spinal bone marrow, intervertebral disks, leptomeninges and the spinal cord itself. Crucial imaging patterns of typical spinal infections are displayed and illustrated by clinical case studies. We present pyogenic, granulomatous and postoperative variants of spondylodicitis, spinal epidural abscess, spinal meningitis and spinal cord infections. The importance of intravenous contrastmedia application is pointed out. (orig.) [de

  17. Pre-procedural antibiotics for endoscopic urological procedures: Initial experience in individuals with spinal cord injury and asymptomatic bacteriuria.

    Science.gov (United States)

    Chong, Julio T; Klausner, Adam P; Petrossian, Albert; Byrne, Michael D; Moore, Jewel R; Goetz, Lance L; Gater, David R; Grob, B Mayer

    2015-03-01

    The objective of this study was to compare the safety, efficacy, quality-of-life impact, and costs of a single dose or a longer course of pre-procedural antibiotics prior to elective endoscopic urological procedures in individuals with spinal cord injury and disorders (SCI/D) and asymptomatic bacteriuria. A prospective observational study. Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA. Sixty persons with SCI/D and asymptomatic bacteriuria scheduled to undergo elective endoscopic urological procedures. A single pre-procedural dose of antibiotics vs. a 3-5-day course of pre-procedural antibiotics. Objective and subjective measures of health, costs, and quality of life. There were no significant differences in vital signs, leukocytosis, adverse events, and overall satisfaction in individuals who received short-course vs. long-course antibiotics. There was a significant decrease in antibiotic cost (33.1 ± 47.6 vs. 3.6 ± 6.1 US$, P = 0.01) for individuals in the short-course group. In addition, there was greater pre-procedural anxiety (18 vs. 0%, P antibiotics. SCI/D individuals with asymptomatic bacteriuria may be able to safely undergo most endoscopic urological procedures with a single dose of pre-procedural antibiotics. However, further research is required and even appropriate pre-procedural antibiotics may not prevent severe infections.

  18. A Cognitive Analysis of Armor Procedural Task Training. Technical Report 605.

    Science.gov (United States)

    Morrison, John E.; Goldberg, Stephen L.

    Traditional and performance-oriented approaches to procedural training were compared, and the deficiencies were identified. A cognitive interpretation of procedural learning was advanced, and training implications were considered. Representative armor procedures were analyzed to derive the underlying memory structures required for recall. Findings…

  19. Analysis of half diallel mating designs I: a practical analysis procedure for ANOVA approximation.

    Science.gov (United States)

    G.R. Johnson; J.N. King

    1998-01-01

    Procedures to analyze half-diallel mating designs using the SAS statistical package are presented. The procedure requires two runs of PROC and VARCOMP and results in estimates of additive and non-additive genetic variation. The procedures described can be modified to work on most statistical software packages which can compute variance component estimates. The...

  20. 77 FR 7240 - Proposed Collection; Comment Request for Revenue Procedure 97-15

    Science.gov (United States)

    2012-02-10

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Revenue Procedure 97-15 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for.... Revenue Procedure Number: Revenue Procedure 97-15. Abstract: This information is required by the Internal...

  1. Adequate procedures for specific exams

    International Nuclear Information System (INIS)

    Staevie, G.L.G.; Gattringer, D.K.; Dal Mas, C.R.; Tessman, M.

    1996-01-01

    Some ideal procedures for specific radiographic exams are briefly presented. The aim is to improve the quality standard, establishing a specific method for each exam in order to decrease films waste and reduce the patient dose exposure

  2. Soil Gas Sampling Operating Procedure

    Science.gov (United States)

    EPA Region 4 Science and Ecosystem Support Division (SESD) document that describes general and specific procedures, methods, and considerations when collecting soil gas samples for field screening or laboratory analysis.

  3. Surface Environmental Surveillance Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Hanf, RW; Dirkes, RL

    1990-02-01

    This manual establishes the procedures for the collection of environmental samples and the performance of radiation surveys and other field measurements. Responsibilities are defined for those personnel directly involved in the collection of samples and the performance of field measurements.

  4. An Analytical Cost Estimation Procedure

    National Research Council Canada - National Science Library

    Jayachandran, Toke

    1999-01-01

    Analytical procedures that can be used to do a sensitivity analysis of a cost estimate, and to perform tradeoffs to identify input values that can reduce the total cost of a project, are described in the report...

  5. Adolescent test or procedure preparation

    Science.gov (United States)

    ... someone else) during the procedure Playing hand-held video games Using guided imagery Trying other distractions, such as listening to music through headphones, if allowed When possible, let your ...

  6. Environmental protection and procedural law

    International Nuclear Information System (INIS)

    Mutschler, U.

    1978-01-01

    For the power industry which is 'independent of licensing', the Ule/Laubinger statement as well as its discussion on the 52th German legal experts' day are of considerable importance. It is therefore absolutely necessary to critically investigate the statements of this expert's opinion and the considerations on which they are based. This investigation is limited to those licensing procedures which in the terminology of experts, are 'similar to the plan approval procedure'. This applies mainly to the procedures according to paragraph 4 ff of the Federal Act on the Protection Against Nuisances and paragraph 7 of the Atomic Energy Law: Preliminaries publication of documents, inspection of files, public hearing, taking of evidence, persons with special responsibilities, administrative proceedings, actions by associations. The deficiencies in the execution of environmental procedural law is briefly mentioned. The notes in the article refer only to air pollution. (orig./HP) [de

  7. Assisted Medical Procedures (AMP) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Documentation and Development: The AMP was initially being developed as part the Advanced Integrated Clinical System (AICS)-Guided Medical Procedure System for the...

  8. Fusion Imaging for Procedural Guidance.

    Science.gov (United States)

    Wiley, Brandon M; Eleid, Mackram F; Thaden, Jeremy J

    2017-11-27

    The field of percutaneous structural heart interventions has grown tremendously in recent years. This growth has fueled the development of new imaging protocols and technologies in parallel to help facilitate these minimally-invasive procedures. Fusion imaging is an exciting new technology that combines the strength of 2 imaging modalities and has the potential to improve procedural planning and the safety of many commonly performed transcatheter procedures. In this review we discuss the basic concepts of fusion imaging along with the relative strengths and weaknesses of static vs dynamic fusion imaging modalities. This review will focus primarily on echocardiographic-fluoroscopic fusion imaging and its application in commonly performed transcatheter structural heart procedures. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Construction inspection manual of procedures

    Science.gov (United States)

    2009-01-01

    This manual provides highway construction personnel with relevant, practical information in order to perform accurate inspections and provide relevant construction procedural information for the various roadway and structures items of work. It is the...

  10. Training Requirements and Information Management System

    Energy Technology Data Exchange (ETDEWEB)

    Cillan, T.F.; Hodgson, M.A.

    1992-05-01

    This is the software user's guide for the Training Requirements and Information Management System. This guide defines and describes the software operating procedures as they apply to the end user of the software program. This guide is intended as a reference tool for the user who already has an indepth knowledge of the Training Requirements and Information Management System functions and data reporting requirement.

  11. Collected radiochemical and geochemical procedures

    Energy Technology Data Exchange (ETDEWEB)

    Kleinberg, J [comp.

    1990-05-01

    This revision of LA-1721, 4th Ed., Collected Radiochemical Procedures, reflects the activities of two groups in the Isotope and Nuclear Chemistry Division of the Los Alamos National Laboratory: INC-11, Nuclear and radiochemistry; and INC-7, Isotope Geochemistry. The procedures fall into five categories: I. Separation of Radionuclides from Uranium, Fission-Product Solutions, and Nuclear Debris; II. Separation of Products from Irradiated Targets; III. Preparation of Samples for Mass Spectrometric Analysis; IV. Dissolution Procedures; and V. Geochemical Procedures. With one exception, the first category of procedures is ordered by the positions of the elements in the Periodic Table, with separate parts on the Representative Elements (the A groups); the d-Transition Elements (the B groups and the Transition Triads); and the Lanthanides (Rare Earths) and Actinides (the 4f- and 5f-Transition Elements). The members of Group IIIB-- scandium, yttrium, and lanthanum--are included with the lanthanides, elements they resemble closely in chemistry and with which they occur in nature. The procedures dealing with the isolation of products from irradiated targets are arranged by target element.

  12. Integrated sampling procedure for metabolome analysis.

    Science.gov (United States)

    Schaub, Jochen; Schiesling, Carola; Reuss, Matthias; Dauner, Michael

    2006-01-01

    Metabolome analysis, the analysis of large sets of intracellular metabolites, has become an important systems analysis method in biotechnological and pharmaceutical research. In metabolic engineering, the integration of metabolome data with fluxome and proteome data into large-scale mathematical models promises to foster rational strategies for strain and cell line improvement. However, the development of reproducible sampling procedures for quantitative analysis of intracellular metabolite concentrations represents a major challenge, accomplishing (i) fast transfer of sample, (ii) efficient quenching of metabolism, (iii) quantitative metabolite extraction, and (iv) optimum sample conditioning for subsequent quantitative analysis. In addressing these requirements, we propose an integrated sampling procedure. Simultaneous quenching and quantitative extraction of intracellular metabolites were realized by short-time exposure of cells to temperatures unit operations into a one unit operation, (ii) the avoidance of any alteration of the sample due to chemical reagents in quenching and extraction, and (iii) automation. A sampling frequency of 5 s(-)(1) and an overall individual sample processing time faster than 30 s allow observing responses of intracellular metabolite concentrations to extracellular stimuli on a subsecond time scale. Recovery and reliability of the unit operations were analyzed. Impact of sample conditioning on subsequent IC-MS analysis of metabolites was examined as well. The integrated sampling procedure was validated through consistent results from steady-state metabolite analysis of Escherichia coli cultivated in a chemostat at D = 0.1 h(-)(1).

  13. No. 247-Antibiotic Prophylaxis in Obstetric Procedures.

    Science.gov (United States)

    van Schalkwyk, Julie; Van Eyk, Nancy

    2017-09-01

    To review the evidence and provide recommendations on antibiotic prophylaxis for obstetrical procedures. Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in obstetrical procedures. Published literature was retrieved through searches of Medline and The Cochrane Library on the topic of antibiotic prophylaxis in obstetrical procedures. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and articles published from January 1978 to June2009 were incorporated in the guideline. Current guidelines published by the American College of Obstetrics and Gynecology were also incorporated. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of this guideline should reduce the cost and harm resulting from the administration of antibiotics when they are not required and the harm resulting from failure to administer antibiotics when they would be beneficial. RECOMMENDATIONS. Copyright © 2017. Published by Elsevier Inc.

  14. OCRWM procedure for reporting software baseline change information

    International Nuclear Information System (INIS)

    1994-07-01

    The purpose of this procedure is to establish a requirement and method for participant organizations to report software baseline change information to the M ampersand O Configuration Management (CM) organization for inclusion in the OCRWM Configuration Information System (CIS). (The requirements for performing software configuration management (SCM) are found in the OCRWM Quality Assurance Requirements and Description (QARD) document and in applicable DOE orders, and not in this procedure.) This procedure provides a linkage between each participant's SCM system and the CIS, which may be accessed for identification, descriptive, and contact information pertaining to software released by a participant. Such information from the CIS will enable retrieval of details and copies of software code and documentation from the participant SCM system

  15. From document to database: modernizing requirements management

    International Nuclear Information System (INIS)

    Giajnorio, J.; Hamilton, S.

    2007-01-01

    The creation, communication, and management of design requirements are central to the successful completion of any large engineering project, both technically and commercially. Design requirements in the Canadian nuclear industry are typically numbered lists in multiple documents created using word processing software. As an alternative, GE Nuclear Products implemented a central requirements management database for a major project at Bruce Power. The database configured the off-the-shelf software product, Telelogic Doors, to GE's requirements structure. This paper describes the advantages realized by this scheme. Examples include traceability from customer requirements through to test procedures, concurrent engineering, and automated change history. (author)

  16. The role the safety analysis report and other documents in the licensing procedure in the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Albrecht, E.; Ballhaus, S.

    1975-01-01

    Legal requirements for the licensing procedure, requirements for and preparation of licensing documents, authorities and experts participating in the licensing procedure, course of the atomic licensing procedure e.g. application for construction and operation, public hearing, site and concept license, partial licenses. (HP) [de

  17. 118-B-1 excavation treatability test procedures

    International Nuclear Information System (INIS)

    Frain, J.M.

    1994-01-01

    This treatability study has two purposes: to support development of the approach to be used for burial ground remediation, and to provide specific engineering information for the design of burial grounds receiving waste generated from the 100 Area removal actions. Data generated from this test will also provide performance and cost information necessary for detailed analysis of alternatives for burial ground remediation. Further details on the test requirements, milestones and data quality objectives are described in detail in the 118-B-1 Excavation Treatability Test Plan (DOE/RL-94-43). These working procedures are intended for use by field personnel to implement the requirements of the milestone. A copy of the detailed Test Plan will be kept on file at the on-site field support trailer, and will be available for review by field personnel

  18. 118-B-1 excavation treatability test procedures

    Energy Technology Data Exchange (ETDEWEB)

    Frain, J.M.

    1994-08-01

    This treatability study has two purposes: to support development of the approach to be used for burial ground remediation, and to provide specific engineering information for the design of burial grounds receiving waste generated from the 100 Area removal actions. Data generated from this test will also provide performance and cost information necessary for detailed analysis of alternatives for burial ground remediation. Further details on the test requirements, milestones and data quality objectives are described in detail in the 118-B-1 Excavation Treatability Test Plan (DOE/RL-94-43). These working procedures are intended for use by field personnel to implement the requirements of the milestone. A copy of the detailed Test Plan will be kept on file at the on-site field support trailer, and will be available for review by field personnel.

  19. Equipment Operational Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Greenwalt, B; Henderer, B; Hibbard, W; Mercer, M

    2009-06-11

    The Iraq Department of Border Enforcement is rich in personnel, but poor in equipment. An effective border control system must include detection, discrimination, decision, tracking and interdiction, capture, identification, and disposition. An equipment solution that addresses only a part of this will not succeed, likewise equipment by itself is not the answer without considering the personnel and how they would employ the equipment. The solution should take advantage of the existing in-place system and address all of the critical functions. The solutions are envisioned as being implemented in a phased manner, where Solution 1 is followed by Solution 2 and eventually by Solution 3. This allows adequate time for training and gaining operational experience for successively more complex equipment. Detailed descriptions of the components follow the solution descriptions. Solution 1 - This solution is based on changes to CONOPs, and does not have a technology component. It consists of observers at the forts and annexes, forward patrols along the swamp edge, in depth patrols approximately 10 kilometers inland from the swamp, and checkpoints on major roads. Solution 2 - This solution adds a ground sensor array to the Solution 1 system. Solution 3 - This solution is based around installing a radar/video camera system on each fort. It employs the CONOPS from Solution 1, but uses minimal ground sensors deployed only in areas with poor radar/video camera coverage (such as canals and streams shielded by vegetation), or by roads covered by radar but outside the range of the radar associated cameras. This document provides broad operational requirements for major equipment components along with sufficient operational details to allow the technical community to identify potential hardware candidates. Continuing analysis will develop quantities required and more detailed tactics, techniques, and procedures.

  20. Procedures for Calculating Residential Dehumidification Loads

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Jon [National Renewable Energy Lab. (NREL), Golden, CO (United States); Booten, Chuck [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-06-01

    Residential building codes and voluntary labeling programs are continually increasing the energy efficiency requirements of residential buildings. Improving a building's thermal enclosure and installing energy-efficient appliances and lighting can result in significant reductions in sensible cooling loads leading to smaller air conditioners and shorter cooling seasons. However due to fresh air ventilation requirements and internal gains, latent cooling loads are not reduced by the same proportion. Thus, it's becoming more challenging for conventional cooling equipment to control indoor humidity at part-load cooling conditions and using conventional cooling equipment in a non-conventional building poses the potential risk of high indoor humidity. The objective of this project was to investigate the impact the chosen design condition has on the calculated part-load cooling moisture load, and compare calculated moisture loads and the required dehumidification capacity to whole-building simulations. Procedures for sizing whole-house supplemental dehumidification equipment have yet to be formalized; however minor modifications to current Air-Conditioner Contractors of America (ACCA) Manual J load calculation procedures are appropriate for calculating residential part-load cooling moisture loads. Though ASHRAE 1% DP design conditions are commonly used to determine the dehumidification requirements for commercial buildings, an appropriate DP design condition for residential buildings has not been investigated. Two methods for sizing supplemental dehumidification equipment were developed and tested. The first method closely followed Manual J cooling load calculations; whereas the second method made more conservative assumptions impacting both sensible and latent loads.