WorldWideScience

Sample records for bioequivalence requirements procedures

  1. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  2. Bioequivalence of azathioprine products.

    Science.gov (United States)

    Baker, Daniel E

    2003-01-01

    All azathioprine oral tablets are considered bioequivalent by the Food and Drug Administration based on traditional testing. However, since these tests were conducted, it has been determined that some patients have a deficiency of the enzyme most responsible for the metabolism of 6-mercaptopurine-thiopurine methyltransferase (TPMT). Azathioprine is rapidly converted to 6-mercaptopurine, its active metabolite. So it is possible that differences in TPMT activity may influence the bioequivalence of azathioprine products among individuals, especially those patients deficient in TPMT enzyme activity. However, this possibility has not been evaluated.

  3. [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.

  4. Licensing procedure and requirements in the FRG

    International Nuclear Information System (INIS)

    Brosche, D.

    1981-01-01

    The investigations of the different dynamic stresses of pressure suppression systems after the Wuergassen incident in 1972 and their theoretical and experimental solutions required an extraordinary effort from all participants of the licensing procedures. As a consequence of these new problems a lot of mathematical models and computer codes had been developed and a lot of experimental work had been performed. Numerous highly qualified scientists and engineers had been involved for a long time in the licensing procedures and innumerable discussions had been necessary. These investigations and discussions had a great influence on the licensing procedures and on the project running. Too pessimistic assumptions and wrong interpretations of experiments led to fictitious problems and a lot of time and money was necessary to overcome these difficulties. Finally at 1977 it could be proved that the construction was able to control stresses so that additional investigations were not necessary. (orig./HP)

  5. 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

  6. 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.

  7. 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...

  8. 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.

  9. Cognition and procedure representational requirements for predictive human performance models

    Science.gov (United States)

    Corker, K.

    1992-01-01

    Models and modeling environments for human performance are becoming significant contributors to early system design and analysis procedures. Issues of levels of automation, physical environment, informational environment, and manning requirements are being addressed by such man/machine analysis systems. The research reported here investigates the close interaction between models of human cognition and models that described procedural performance. We describe a methodology for the decomposition of aircrew procedures that supports interaction with models of cognition on the basis of procedures observed; that serves to identify cockpit/avionics information sources and crew information requirements; and that provides the structure to support methods for function allocation among crew and aiding systems. Our approach is to develop an object-oriented, modular, executable software representation of the aircrew, the aircraft, and the procedures necessary to satisfy flight-phase goals. We then encode in a time-based language, taxonomies of the conceptual, relational, and procedural constraints among the cockpit avionics and control system and the aircrew. We have designed and implemented a goals/procedures hierarchic representation sufficient to describe procedural flow in the cockpit. We then execute the procedural representation in simulation software and calculate the values of the flight instruments, aircraft state variables and crew resources using the constraints available from the relationship taxonomies. The system provides a flexible, extensible, manipulative and executable representation of aircrew and procedures that is generally applicable to crew/procedure task-analysis. The representation supports developed methods of intent inference, and is extensible to include issues of information requirements and functional allocation. We are attempting to link the procedural representation to models of cognitive functions to establish several intent inference methods

  10. 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.

  11. 44 CFR 17.630 - Certification requirements and procedures.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Certification requirements and procedures. 17.630 Section 17.630 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE...

  12. 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 ...

  13. Development to requirements for a procedures software tool

    International Nuclear Information System (INIS)

    Yasutake, J.Y.; Hachiro Isoda

    1993-01-01

    In 1989, the Electric Power Research Institute (EPRI) and the Central Research Institute of the Electric Power Industry (CRIEPI) in Japan initiated a joint research program to investigate various interventions to reduce personnel errors and inefficiencies in the maintenance of nuclear power plants. This program, consisting of several interrelated projects, was initiated because of the mutual recognition of the importance of the human element in the efficient and safe operation of utilities and the continuing need to enhance personnel performance to sustain plant safety and availability. This paper summarizes one of the projects, jointly funded by EPRI and CRIEPI, to analyze the requirements for, and prepare a functional description of, a procedures software tool (PST). The primary objective of this project was to develop a description of the features and functions of a software tool that would help procedure writers to improve the quality of maintenance and testing procedures, thereby enhancing the performance of both procedure writers and maintenance personnel

  14. 46 CFR 272.42 - Audit requirements and procedures.

    Science.gov (United States)

    2010-10-01

    ... procedures. (a) Required audit. In connection with the audit of the Operator's subsidizable expenses, the... of audit results. Upon completion of the audit by the Office of Inspector General, the MARAD Office of Financial Approvals shall notify the Operator of the audit results, including any items disallowed...

  15. 16 CFR 1501.4 - Size requirements and test procedure.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Size requirements and test procedure. 1501.4 Section 1501.4 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT.... The metric approximations are included only for convenience.) (b)(1) Place the article, without...

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Bioequivalence assessment of two formulations of ibuprofen

    Directory of Open Access Journals (Sweden)

    Al-Talla ZA

    2011-10-01

    , therefore, Doloraz was considered bioequivalent to Brufen. Keywords: ibuprofen, bioequivalence study, pharmacokinetics

  1. 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.

  2. 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...

  3. Standardized Procedure Content And Data Structure Based On Human Factors Requirements For Computer-Based Procedures

    International Nuclear Information System (INIS)

    Bly, Aaron; Oxstrand, Johanna; Le Blanc, Katya L

    2015-01-01

    Most activities that involve human interaction with systems in a nuclear power plant are guided by procedures. Traditionally, the use of procedures has been a paper-based process that supports safe operation of the nuclear power industry. However, the nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. Advances in digital technology make computer-based procedures (CBPs) a valid option that provides further enhancement of safety by improving human performance related to procedure use. The transition from paper-based procedures (PBPs) to CBPs creates a need for a computer-based procedure system (CBPS). A CBPS needs to have the ability to perform logical operations in order to adjust to the inputs received from either users or real time data from plant status databases. Without the ability for logical operations the procedure is just an electronic copy of the paper-based procedure. In order to provide the CBPS with the information it needs to display the procedure steps to the user, special care is needed in the format used to deliver all data and instructions to create the steps. The procedure should be broken down into basic elements and formatted in a standard method for the CBPS. One way to build the underlying data architecture is to use an Extensible Markup Language (XML) schema, which utilizes basic elements to build each step in the smart procedure. The attributes of each step will determine the type of functionality that the system will generate for that step. The CBPS will provide the context for the step to deliver referential information, request a decision, or accept input from the user. The XML schema needs to provide all data necessary for the system to accurately perform each step without the need for the procedure writer to reprogram the CBPS. The research team at the Idaho National Laboratory has developed a prototype CBPS for field workers as well as the

  4. Standardized Procedure Content And Data Structure Based On Human Factors Requirements For Computer-Based Procedures

    Energy Technology Data Exchange (ETDEWEB)

    Bly, Aaron; Oxstrand, Johanna; Le Blanc, Katya L

    2015-02-01

    Most activities that involve human interaction with systems in a nuclear power plant are guided by procedures. Traditionally, the use of procedures has been a paper-based process that supports safe operation of the nuclear power industry. However, the nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. Advances in digital technology make computer-based procedures (CBPs) a valid option that provides further enhancement of safety by improving human performance related to procedure use. The transition from paper-based procedures (PBPs) to CBPs creates a need for a computer-based procedure system (CBPS). A CBPS needs to have the ability to perform logical operations in order to adjust to the inputs received from either users or real time data from plant status databases. Without the ability for logical operations the procedure is just an electronic copy of the paper-based procedure. In order to provide the CBPS with the information it needs to display the procedure steps to the user, special care is needed in the format used to deliver all data and instructions to create the steps. The procedure should be broken down into basic elements and formatted in a standard method for the CBPS. One way to build the underlying data architecture is to use an Extensible Markup Language (XML) schema, which utilizes basic elements to build each step in the smart procedure. The attributes of each step will determine the type of functionality that the system will generate for that step. The CBPS will provide the context for the step to deliver referential information, request a decision, or accept input from the user. The XML schema needs to provide all data necessary for the system to accurately perform each step without the need for the procedure writer to reprogram the CBPS. The research team at the Idaho National Laboratory has developed a prototype CBPS for field workers as well as the

  5. 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....

  6. 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.

  7. 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...

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

    Science.gov (United States)

    1979-01-01

    stress versus cycles to failure (S/N) method of testing and verification. A mi..iimum of six test specimens is required to establish the mean curve with...Approach) A.D. Hall B.Sc., C.Eng., M.R.Ae.S. 4 Chief Stress Engineer (Dynamic Components) Westland Helicopters Limited, Yeovil, Somerset, England...airworthiness requirements concerning the fatifue strength of British milltary nelicopters are embodied in the U.K. Ministry Documents Aviation Publication

  9. 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...

  10. 30 CFR 14.4 - Application procedures and requirements.

    Science.gov (United States)

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS... conveyor belt for use in underground coal mines must include the information below, except any information...) A technical description of the conveyor belt, which includes: (i) Trade name or identification...

  11. 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; injector assembly and nozzle details; and any surfaces that form the combustion chamber or part thereof..., EVALUATION, AND APPROVAL OF MINING PRODUCTS APPROVAL REQUIREMENTS FOR PERMISSIBLE MOBILE DIESEL-POWERED...

  12. 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...

  13. 76 FR 66721 - New Policies and Procedural Requirements for the Electronic Submission of Discretionary Grant...

    Science.gov (United States)

    2011-10-27

    ... electronic submission of discretionary grant applications through the government-wide grants application site... Procedural Requirements for the Electronic Submission of Discretionary Grant Applications AGENCY: Division of... requirements for the electronic submission of discretionary grant applications. Overview Information: The...

  14. 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.

  15. Bioequivalence study on two brands of 10% enrofloxacin oral ...

    African Journals Online (AJOL)

    A bioequivalence of two brands of 10% enrofloxacin was tested in broiler chickens using a parallel design at 20 mg/kg bodyweight orally. Blood was sampled before and after drug administration for 24 hours. Plasma enrofloxacin concentrations were analyzed using microbiological assay. Peak plasma concentrations ...

  16. 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

  17. 15 CFR 291.6 - Additional requirements; Federal policies and procedures.

    Science.gov (United States)

    2010-01-01

    ... and Foreign Trade NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE NIST... requirements; Federal policies and procedures. Recipients and subrecipients are subject to all Federal laws and Federal and Department of Commerce policies, regulations, and procedures applicable to Federal financial...

  18. Development of procedural requirements for life extension of nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hun; Son, Moon Kyu [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Ham, Cheol Hun [The Catholic University of Korea, Seoul (Korea, Republic of); Chang, Keun Sun [Sunmoon Univ., Asan (Korea, Republic of); Paek, Won Phil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of); Cheong, Ji Hwan [Baekseok College Cultural Studies, Cheonan (Korea, Republic of)

    2001-03-15

    Current status of regulatory aspects of life extension and upgrading of NPPs is reviewed for major foreign countries. Most countries require similar technical requirements; however, procedural aspects differ country by country. Regulatory systems suitable for NPP life extension is investigated. The procedure and requirements for reassessment of design life should be established first; then it can be incorporated into the PSR system. The concept of 'Current Licensing Basis (CLB)' can be adopted in Korea, but further elaboration for terms and definitions is needed for common understanding between interested groups. The procedure for maintenance and backfitting should also be improved. The Systems, Structures, and Components (SSCs) that require development of regulatory requirements for life extension are identified based on extensive analysis of foreign experiences. By analyzing the rules and regulations related to life extension. Basic directions are suggested to harmonize or establish regulatory systems for life extension, two-step licensing, PSR, and backfitting.

  19. 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...... 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...

  20. 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.

  1. Regulatory and clinical aspects of psychotropic medicinal products bioequivalence.

    Science.gov (United States)

    Bałkowiec-Iskra, Ewa; Cessak, Grzegorz; Kuzawińska, Olga; Sejbuk-Rozbicka, Katarzyna; Rokita, Konrad; Mirowska-Guzel, Dagmara

    2015-07-01

    Introduction of generic medicinal products to the market has increased access to modern therapies but also enabled significant reduction in their cost, leading to containment of public expenditures on medicinal products reimbursement. The critical assessment of bioequivalence of any reference medicinal product and its counterpart is based on comparison of their rate and extent of absorption. It is assumed that two medicinal products are bioequivalent when their rate and extent of absorption do not show significant differences when administered at the same dose under similar experimental conditions. Bioequivalent medicinal products are declared to be also therapeutically equivalent and can be used interchangeably. However, despite regulatory declaration, switching from reference to generic drugs is often associated with concerns of healthcare providers about decreased treatment effectiveness or occurrence of adverse drug reactions. The aim of this article is to provide a description of rules that guide registration of generic medicinal products in the European Union and to analyze specific examples from the scientific literature concerning therapeutic equivalence of reference and generic antidepressant and antipsychotic medicinal products. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  2. 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... Supplementary specific procedural requirements under HUD building products certification program for solid fuel... fireplace stoves certified under the HUD Building Products Certification Program shall be designed...

  3. Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs.

    Science.gov (United States)

    van Gelder, Teun; Gabardi, Steven

    2013-08-01

    Within the field of solid organ transplantation, the patents for a number of immunosuppressive drugs have expired in the last few years. Tacrolimus, cyclosporine, and mycophenolate mofetil are now available as generic drugs. In some countries, the market penetration of these generic formulations is as high as 70%, whereas in some other countries, this figure is below 10%. Several professional societies have published position papers on the risks and benefits of generic substitution of immunosuppressive drugs. It often appears that transplant professionals are not fully aware of the requirements for registration of generic drugs. This article describes the registration requirements with a focus on bioequivalence testing, the strengths and weaknesses in this process, and the differences between Europe and the US. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  4. Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

    Science.gov (United States)

    Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

    2016-01-01

    Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  5. 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.

  6. 77 FR 66621 - Draft Guidance for Industry on Bioequivalence Recommendation for Lenalidomide Capsules; Availability

    Science.gov (United States)

    2012-11-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0433; (formerly Docket No. 2007D-0169)] Draft Guidance for Industry on Bioequivalence Recommendation for...) Acceptable fasting and fed bioequivalence studies on the 25 mg strength, (2) proportional similarity of the...

  7. 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

  8. 19 CFR 101.9 - Test programs or procedures; alternate requirements.

    Science.gov (United States)

    2010-04-01

    ... basis for selecting participants. (b) NCAP testing. For purposes of conducting an approved test program or procedure designed to evaluate planned components of the National Customs Automation Program (NCAP... publication requirement. For tests affecting the NCAP, notice shall be published in the Federal Register not...

  9. 78 FR 41298 - Children's Products Containing Lead; Procedures and Requirements for Exclusions From Lead Limits...

    Science.gov (United States)

    2013-07-10

    ... on materials previously submitted in connection with a petition for exclusion under this section. In... 16 CFR 1500.90 to provide procedures and requirements for evaluating products or materials for... and comment rulemaking, section 553 of the APA provides an exception when the agency, for good cause...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 75 FR 76254 - Official Performance and Procedural Requirements for Grain Weighing Equipment and Related Grain...

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF AGRICULTURE Grain Inspection, Packers and Stockyards Administration 7 CFR Part 802 [Docket GIPSA-2010-FGIS-0012] RIN 0580-AB19 Official Performance and Procedural Requirements for Grain Weighing Equipment and Related Grain Handling Systems AGENCY: Grain Inspection, Packers and Stockyards...

  2. 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...

  3. Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.

    Science.gov (United States)

    Cho, Kyung-Jin; Cho, Wonkyung; Cha, Kwang-Ho; Park, Junsung; Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

    2010-01-01

    In the present study two different formulations containing 50 mg itopride HCl (N-[4-12-(dimethylamino)ethoxylbenzyl]-3,4-dimethoxybenzamide HCl, CAS 122898-67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h. The serum concentrations of itopride HCl were determined using a specific and sensitive HPLC method with fluorescence detection. The detection limit of itopride HCl was 5 ng/ml and no endogenous compounds were found to interfere with analysis. The mean AUC(0-4h), AUC(0 --> infinity), C(max), T(max) and T1/2 were 865.28 ng x h/ml, 873.04 ng x h/ml, 303.72 ng/ml, 0.75 h, and 2.95 h, respectively, for the test formulations, and 833.00 ng x h/ml, 830.97 ng x h/ml, 268.01 ng/ml, 0.78 h, and 2.83 h, respectively, for the reference formulation. Both primary target parameters AUC(0 --> infinity) and C(max) were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of AUC(0 --> infinity) and C(max) were 100.57%-109.56% and 105.46%-121.18%, respectively, and were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of itopride HCl are considered to be bioequivalent.

  4. Bioequivalence of a new cyclosporine a formulation to Neoral.

    Science.gov (United States)

    David-Neto, Elias; Kakehashi, Erica; Alves, Cristiane Feres; Pereira, Lilian M; de Castro, Maria Cristina R; de Mattos, Renata Maciel; Sumita, Nairo Massakazu; Romano, Paschoalina; Mendes, Maria Elizabete; Nahas, William Carlos; Ianhez, Luiz Estevam

    2004-02-01

    New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.

  5. 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.

  6. Update on dexmedetomidine: use in nonintubated patients requiring sedation for surgical procedures

    Directory of Open Access Journals (Sweden)

    Mohanad Shukry

    2010-03-01

    Full Text Available Mohanad Shukry, Jeffrey A MillerUniversity of Oklahoma Health Sciences Center, Department of Anesthesiology, Children’s Hospital of Oklahoma, Oklahoma City, OK, USAAbstract: Dexmedetomidine was introduced two decades ago as a sedative and supplement to sedation in the intensive care unit for patients whose trachea was intubated. However, since that time dexmedetomidine has been commonly used as a sedative and hypnotic for patients undergoing procedures without the need for tracheal intubation. This review focuses on the application of dexmedetomidine as a sedative and/or total anesthetic in patients undergoing procedures without the need for tracheal intubation. Dexmedetomidine was used for sedation in monitored anesthesia care (MAC, airway procedures including fiberoptic bronchoscopy, dental procedures, ophthalmological procedures, head and neck procedures, neurosurgery, and vascular surgery. Additionally, dexmedetomidine was used for the sedation of pediatric patients undergoing different type of procedures such as cardiac catheterization and magnetic resonance imaging. Dexmedetomidine loading dose ranged from 0.5 to 5 μg kg-1, and infusion dose ranged from 0.2 to 10 μg kg-1 h-1. Dexmedetomidine was administered in conjunction with local anesthesia and/or other sedatives. Ketamine was administered with dexmedetomidine and opposed its bradycardiac effects. Dexmedetomidine may by useful in patients needing sedation without tracheal intubation. The literature suggests potential use of dexmedetomidine solely or as an adjunctive agent to other sedation agents. Dexmedetomidine was especially useful when spontaneous breathing was essential such as in procedures on the airway, or when sudden awakening from sedation was required such as for cooperative clinical examination during craniotomies.Keywords: dexmedetomidine, sedation, nonintubated patients

  7. 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

  8. System Requirements Analysis for a Computer-based Procedure in a Research Reactor Facility

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jaek Wan; Jang, Gwi Sook; Seo, Sang Moon; Shin, Sung Ki [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    This can address many of the routine problems related to human error in the use of conventional, hard-copy operating procedures. An operating supporting system is also required in a research reactor. A well-made CBP can address the staffing issues of a research reactor and reduce the human errors by minimizing the operator's routine tasks. A CBP for a research reactor has not been proposed yet. Also, CBPs developed for nuclear power plants have powerful and various technical functions to cover complicated plant operation situations. However, many of the functions may not be required for a research reactor. Thus, it is not reasonable to apply the CBP to a research reactor directly. Also, customizing of the CBP is not cost-effective. Therefore, a compact CBP should be developed for a research reactor. This paper introduces high level requirements derived by the system requirements analysis activity as the first stage of system implementation. Operation support tools are under consideration for application to research reactors. In particular, as a full digitalization of the main control room, application of a computer-based procedure system has been required as a part of man-machine interface system because it makes an impact on the operating staffing and human errors of a research reactor. To establish computer-based system requirements for a research reactor, this paper addressed international standards and previous practices on nuclear plants.

  9. Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

    Science.gov (United States)

    Shahiwala, Aliasgar; Zarar, Aisha

    2018-01-01

    In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Current Mobile Payment Procedures on the German Market from the View of Customer Requirements

    OpenAIRE

    Pousttchi, Key; Zenker, M.

    2003-01-01

    The key to mobile payment acceptance is in the hands of customers. In this paper we use the results of the mobile payment survey MP1 in order to identify and roughly weigh the most relevant acceptance criteria. The outcome of the paper is an evaluation scheme containing the covered payment scenarios, important main criteria (security, costs and convenience) and additional functionality requirements for each MP procedure. The scheme is based on empirical results and can assess a given MP proce...

  11. 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.

  12. Environmental radiation monitoring during visits of nuclear powered warships to Australian ports: requirements, arrangements and procedures

    International Nuclear Information System (INIS)

    1988-05-01

    The Commonwealth Government has determined conditions to be met when nuclear powered warships visit Australian ports. These conditions include a requirement that appropriate State/Territory and Commonwealth authorities provide a radiation monitoring program to determine whether any radioactivity has been discharged or accidently released from a nuclear powered warship in port; to determine actual or potential levels of any consequent exposure to radiation of members of the public; and to provide this information within a timescale that allows remedial action to be taken. Part 1 of this document sets out the requirements of a radiation monitoring program capable of meeting these objectives. The fundamental arrangements and procedures for implementing the requirements are presented at Part 2 and provide a basis for the development of fully detailed, port specific, radiation monitoring programs

  13. Current Challenges in Bioequivalence, Quality, and Novel Assessment Technologies for Topical Products

    DEFF Research Database (Denmark)

    Yacobi, Avraham; Shah, Vinod P; Bashaw, Edward D

    2014-01-01

    This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic...

  14. 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

  15. 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.

  16. 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.

  17. [Bioequivalence of dermatological topical medicines:the Brazilian scenario and the challenges for health surveillance].

    Science.gov (United States)

    Soares, Kelen Carine Costa; Moraes, Marcelo Vogler; Gelfuso, Guilherme Martins; Gratieri, Taís

    2015-11-01

    The comparative evaluation required for the registration of generic topical medicines in Brazil is conducted by means of a pharmaceutical equivalence study, which merely assesses the physical/chemical and microbiological parameters of the formulations. At the international level, clinical or pharmacodynamic studies are now being required to prove the efficacy and safety of semisolid topical generic formulations. This work presents a comparison of the different requirements for the registration of topical formulations, taking into consideration the various regulatory authorities, and presents a survey of topical medicines registered in Brazil prior to 2013. The survey revealed that in comparison with the USA there were many more copies of these formulations registered in Brazil. This fact, together with the large number of studies in the literature showing the lack of bioequivalence of topical medication, is clear proof of the major importance of the need to realign Brazilian legislation with respect to the technical requirements for the registration of generic and similar medication for dermatological topical application in Brazil.

  18. 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.

  19. Required number of records for ASCE/SEI 7 ground-motion scaling procedure

    Science.gov (United States)

    Reyes, Juan C.; Kalkan, Erol

    2011-01-01

    The procedures and criteria in 2006 IBC (International Council of Building Officials, 2006) and 2007 CBC (International Council of Building Officials, 2007) for the selection and scaling ground-motions for use in nonlinear response history analysis (RHA) of structures are based on ASCE/SEI 7 provisions (ASCE, 2005, 2010). According to ASCE/SEI 7, earthquake records should be selected from events of magnitudes, fault distance, and source mechanisms that comply with the maximum considered earthquake, and then scaled so that the average value of the 5-percent-damped response spectra for the set of scaled records is not less than the design response spectrum over the period range from 0.2Tn to 1.5Tn sec (where Tn is the fundamental vibration period of the structure). If at least seven ground-motions are analyzed, the design values of engineering demand parameters (EDPs) are taken as the average of the EDPs determined from the analyses. If fewer than seven ground-motions are analyzed, the design values of EDPs are taken as the maximum values of the EDPs. ASCE/SEI 7 requires a minimum of three ground-motions. These limits on the number of records in the ASCE/SEI 7 procedure are based on engineering experience, rather than on a comprehensive evaluation. This study statistically examines the required number of records for the ASCE/SEI 7 procedure, such that the scaled records provide accurate, efficient, and consistent estimates of" true" structural responses. Based on elastic-perfectly-plastic and bilinear single-degree-of-freedom systems, the ASCE/SEI 7 scaling procedure is applied to 480 sets of ground-motions. The number of records in these sets varies from three to ten. The records in each set were selected either (i) randomly, (ii) considering their spectral shapes, or (iii) considering their spectral shapes and design spectral-acceleration value, A(Tn). As compared to benchmark (that is, "true") responses from unscaled records using a larger catalog of ground

  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. Large-volume injection of sample diluents not miscible with the mobile phase as an alternative approach in sample preparation for bioanalysis: an application for fenspiride bioequivalence.

    Science.gov (United States)

    Medvedovici, Andrei; Udrescu, Stefan; Albu, Florin; Tache, Florentin; David, Victor

    2011-09-01

    Liquid-liquid extraction of target compounds from biological matrices followed by the injection of a large volume from the organic layer into the chromatographic column operated under reversed-phase (RP) conditions would successfully combine the selectivity and the straightforward character of the procedure in order to enhance sensitivity, compared with the usual approach of involving solvent evaporation and residue re-dissolution. Large-volume injection of samples in diluents that are not miscible with the mobile phase was recently introduced in chromatographic practice. The risk of random errors produced during the manipulation of samples is also substantially reduced. A bioanalytical method designed for the bioequivalence of fenspiride containing pharmaceutical formulations was based on a sample preparation procedure involving extraction of the target analyte and the internal standard (trimetazidine) from alkalinized plasma samples in 1-octanol. A volume of 75 µl from the octanol layer was directly injected on a Zorbax SB C18 Rapid Resolution, 50 mm length × 4.6 mm internal diameter × 1.8 µm particle size column, with the RP separation being carried out under gradient elution conditions. Detection was made through positive ESI and MS/MS. Aspects related to method development and validation are discussed. The bioanalytical method was successfully applied to assess bioequivalence of a modified release pharmaceutical formulation containing 80 mg fenspiride hydrochloride during two different studies carried out as single-dose administration under fasting and fed conditions (four arms), and multiple doses administration, respectively. The quality attributes assigned to the bioanalytical method, as resulting from its application to the bioequivalence studies, are highlighted and fully demonstrate that sample preparation based on large-volume injection of immiscible diluents has an increased potential for application in bioanalysis.

  2. Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

    Science.gov (United States)

    Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

    2013-12-01

    Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

  3. 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.

  4. 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.

  5. Metadata requirements for results of diagnostic imaging procedures: a BIIF profile to support user applications

    Science.gov (United States)

    Brown, Nicholas J.; Lloyd, David S.; Reynolds, Melvin I.; Plummer, David L.

    2002-05-01

    A visible digital image is rendered from a set of digital image data. Medical digital image data can be stored as either: (a) pre-rendered format, corresponding to a photographic print, or (b) un-rendered format, corresponding to a photographic negative. The appropriate image data storage format and associated header data (metadata) required by a user of the results of a diagnostic procedure recorded electronically depends on the task(s) to be performed. The DICOM standard provides a rich set of metadata that supports the needs of complex applications. Many end user applications, such as simple report text viewing and display of a selected image, are not so demanding and generic image formats such as JPEG are sometimes used. However, these are lacking some basic identification requirements. In this paper we make specific proposals for minimal extensions to generic image metadata of value in various domains, which enable safe use in the case of two simple healthcare end user scenarios: (a) viewing of text and a selected JPEG image activated by a hyperlink and (b) viewing of one or more JPEG images together with superimposed text and graphics annotation using a file specified by a profile of the ISO/IEC Basic Image Interchange Format (BIIF).

  6. Comparison of parametric and bootstrap method in bioequivalence test.

    Science.gov (United States)

    Ahn, Byung-Jin; Yim, Dong-Seok

    2009-10-01

    The estimation of 90% parametric confidence intervals (CIs) of mean AUC and Cmax ratios in bioequivalence (BE) tests are based upon the assumption that formulation effects in log-transformed data are normally distributed. To compare the parametric CIs with those obtained from nonparametric methods we performed repeated estimation of bootstrap-resampled datasets. The AUC and Cmax values from 3 archived datasets were used. BE tests on 1,000 resampled datasets from each archived dataset were performed using SAS (Enterprise Guide Ver.3). Bootstrap nonparametric 90% CIs of formulation effects were then compared with the parametric 90% CIs of the original datasets. The 90% CIs of formulation effects estimated from the 3 archived datasets were slightly different from nonparametric 90% CIs obtained from BE tests on resampled datasets. Histograms and density curves of formulation effects obtained from resampled datasets were similar to those of normal distribution. However, in 2 of 3 resampled log (AUC) datasets, the estimates of formulation effects did not follow the Gaussian distribution. Bias-corrected and accelerated (BCa) CIs, one of the nonparametric CIs of formulation effects, shifted outside the parametric 90% CIs of the archived datasets in these 2 non-normally distributed resampled log (AUC) datasets. Currently, the 80~125% rule based upon the parametric 90% CIs is widely accepted under the assumption of normally distributed formulation effects in log-transformed data. However, nonparametric CIs may be a better choice when data do not follow this assumption.

  7. Use of partial AUC (PAUC) to evaluate bioequivalence--a case study with complex absorption: methylphenidate.

    Science.gov (United States)

    Fourie Zirkelbach, Jeanne; Jackson, Andre J; Wang, Yaning; Schuirmann, Donald J

    2013-01-01

    Methylphenidate modified-release products produce early and late peak concentrations critical for treatment of morning and afternoon symptoms of attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE) criteria cannot be applied to these products. The performance of partial area under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were independently evaluated for two products. A two-stage analysis was performed on plasma data for two methylphenidate modified-release products (Product 1 and 2). Simulations using the fitted parameters determined how changes in fast absorption rate constant (K0Fast) and fraction available (F1) affected curve shape and BE determination using Cmax, AUCINF and PAUC. The sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference) ratios for PAUC0-4h are more responsive to both decreases and increases in K0Fast(test) than Product 2. Product 2 showed a greater response in the mean PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased and less response as the value is increased. PAUC estimated curve shape is sensitive to changes in absorption and are product specific, and may require a new PAUC metric for each drug. A non-product specific metric to assess curve shape is warranted.

  8. The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

    Science.gov (United States)

    Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

    2015-01-23

    To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

    Science.gov (United States)

    Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

    2009-01-01

    The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

  10. 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...

  11. A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

    Science.gov (United States)

    Pan, Lin; Belloni, Paula; Ding, Han Ting; Wang, Jianshuang; Rubino, Christopher M; Putnam, Wendy S

    2017-09-01

    Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states. A Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted. Each subject received an 801-mg single dose of pirfenidone as three 267-mg capsules or one 801-mg tablet under fasted and fed conditions. Pirfenidone plasma C max , AUC 0-t and AUC 0-∞ were used to assess bioequivalence. Forty-four subjects were randomized to treatment. The 801-mg tablet in the fasted state met bioequivalence criteria [90% confidence intervals (CI) 80.00-125.00%] for the GLSM ratios of natural log-transformed C max , AUC 0-t and AUC 0-∞ . Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC 0-t and AUC 0-∞ , but slightly exceeded the bioequivalence criteria for the C max (90% CI of 108.26-125.60%). The tablet C max was approximately 17% higher than that of the capsules. In the fed state, the tablet C max , and both AUC 0-t and AUC 0-∞ were reduced by 39% and 17%, respectively, relative to the fasted state. The tablet and capsules had acceptable tolerability profiles. The pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet C max was slightly higher relative to capsules in the fed state, but this is not expected to have a clinically meaningful impact on the benefit-risk profile of pirfenidone. This work was supported by F. Hoffmann-La Roche Ltd.

  12. 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.

  13. Effect of Different Sampling Schedules on Results of Bioavailability and Bioequivalence Studies: Evaluation by Means of Monte Carlo Simulations.

    Science.gov (United States)

    Kano, Eunice Kazue; Chiann, Chang; Fukuda, Kazuo; Porta, Valentina

    2017-08-01

    Bioavailability and bioequivalence study is one of the most frequently performed investigations in clinical trials. Bioequivalence testing is based on the assumption that 2 drug products will be therapeutically equivalent when they are equivalent in the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed and becomes available at the site of drug action. In recent years there has been a significant growth in published papers that use in silico studies based on mathematical simulations to analyze pharmacokinetic and pharmacodynamic properties of drugs, including bioavailability and bioequivalence aspects. The goal of this study is to evaluate the usefulness of in silico studies as a tool in the planning of bioequivalence, bioavailability and other pharmacokinetic assays, e.g., to determine an appropriate sampling schedule. Monte Carlo simulations were used to define adequate blood sampling schedules for a bioequivalence assay comparing 2 different formulations of cefadroxil oral suspensions. In silico bioequivalence studies comparing different formulation of cefadroxil oral suspensions using various sampling schedules were performed using models. An in vivo study was conducted to confirm in silico results. The results of in silico and in vivo bioequivalence studies demonstrated that schedules with fewer sampling times are as efficient as schedules with larger numbers of sampling times in the assessment of bioequivalence, but only if T max is included as a sampling time. It was also concluded that in silico studies are useful tools in the planning of bioequivalence, bioavailability and other pharmacokinetic in vivo assays. © Georg Thieme Verlag KG Stuttgart · New York.

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

    KAUST Repository

    Al-Talla, Zeyad; Akrawi, Sabah H.; Emwas, Abdul-Hamid M.

    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

  15. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Science.gov (United States)

    2013-12-05

    ... exposure measures is suitable for documenting BE (e.g., transdermal delivery systems and certain rectal and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1464] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted...

  16. 78 FR 66743 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability

    Science.gov (United States)

    2013-11-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369] Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability AGENCY... guidance, FDA recommended an in vivo fasting BE study with pharmacokinetic endpoints and in vitro studies...

  17. 75 FR 33311 - Guidance for Industry on Bioequivalence Recommendations for Specific Products; Availability

    Science.gov (United States)

    2010-06-11

    ... available recommendations on how to design product-specific BE studies to support ANDAs. Under this process... thinking on a new process for making available to sponsors FDA guidance on how to design product-specific... ``Bioequivalence Recommendations for Specific Products.'' This guidance describes a new process for making...

  18. 77 FR 10535 - Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations...

    Science.gov (United States)

    2012-02-22

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

  19. 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...

  20. Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

    Science.gov (United States)

    Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

    2013-11-01

    To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers.

    Science.gov (United States)

    Baribeault, David

    2011-08-01

    Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent. In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG. Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%. A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

  2. 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.

  3. 75 FR 31334 - Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's “Required Use...

    Science.gov (United States)

    2010-06-03

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

  4. 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...

  5. [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.

  6. Definition of Specific Functions and Procedural Skills Required by Cuban Specialists in Intensive Care and Emergency Medicine.

    Science.gov (United States)

    Véliz, Pedro L; Berra, Esperanza M; Jorna, Ana R

    2015-07-01

    INTRODUCTION Medical specialties' core curricula should take into account functions to be carried out, positions to be filled and populations to be served. The functions in the professional profile for specialty training of Cuban intensive care and emergency medicine specialists do not include all the activities that they actually perform in professional practice. OBJECTIVE Define the specific functions and procedural skills required of Cuban specialists in intensive care and emergency medicine. METHODS The study was conducted from April 2011 to September 2013. A three-stage methodological strategy was designed using qualitative techniques. By purposive maximum variation sampling, 82 professionals were selected. Documentary analysis and key informant criteria were used in the first stage. Two expert groups were formed in the second stage: one used various group techniques (focus group, oral and written brainstorming) and the second used a three-round Delphi method. In the final stage, a third group of experts was questioned in semistructured in-depth interviews, and a two-round Delphi method was employed to assess priorities. RESULTS Ultimately, 78 specific functions were defined: 47 (60.3%) patient care, 16 (20.5%) managerial, 6 (7.7%) teaching, and 9 (11.5%) research. Thirty-one procedural skills were identified. The specific functions and procedural skills defined relate to the profession's requirements in clinical care of the critically ill, management of patient services, teaching and research at the specialist's different occupational levels. CONCLUSIONS The specific functions and procedural skills required of intensive care and emergency medicine specialists were precisely identified by a scientific method. This product is key to improving the quality of teaching, research, administration and patient care in this specialty in Cuba. The specific functions and procedural skills identified are theoretical, practical, methodological and social contributions to

  7. 21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE... test product and the reference material should be administered to subjects in the fasting state, unless...

  8. 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)

  9. 46 CFR 281.1 - Information and procedure required under liner operating-differential subsidy agreements.

    Science.gov (United States)

    2010-10-01

    ... shall be sent to the Division of Trade Studies, Office of Subsidy Administration, Maritime... in the American insurance market. Therefore, when a renewal of policies or new insurance is under... options (such as facsimile and Internet) for transmission of required information to MARAD, if practicable...

  10. 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...

  11. 26 CFR 1.7519-2T - Required payments-procedures and administration (temporary).

    Science.gov (United States)

    2010-04-01

    ... tax imposed by section 4251 (relating to communications services tax), sections 4261 and 4271... (temporary). 1.7519-2T Section 1.7519-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES The Tax Court § 1.7519-2T Required payments...

  12. 7 CFR Appendix to Subpart C of... - Accounting Methods and Procedures Required of All Borrowers

    Science.gov (United States)

    2010-01-01

    ... Television Services 105 Comprehensive Income—108 Consolidated Financial Statements 106 Cushion of Credit... statements even though this financial information is presented in the parent's consolidated statements. 2. In... consolidated financial statements in accordance with the requirements of Statement No. 94. These consolidated...

  13. 36 CFR 251.54 - Proposal and application requirements and procedures.

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF AGRICULTURE LAND USES Special Uses § 251.54 Proposal and application requirements and... activity does not materially impact the characteristics or functions of the environmentally sensitive...-disposal facilities; (3) The availability of sufficient potable drinking water; (4) The risk of disease...

  14. 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

  15. 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.

  16. 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.

  17. Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

    Science.gov (United States)

    Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

    2012-04-01

    FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

  18. FEDERAL RULEMAKING: Procedural and Analytical Requirements at OSHA and Other Agencies

    Science.gov (United States)

    2001-06-14

    informal rulemaking. Formal rulemaking is used in ratemaking proceedings and in certain other cases when rules are required by statute to be made “on...substantial flexibility regarding how the analyses should be prepared, but also indicates that the analyses should contain certain basic elements and...calendar days, so our review is limited to a description of the issuing agency’s rulemaking actions.25 We also collect basic information about the nonmajor

  19. 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.

  20. Radiological and administrative criteria and procedures required by the Radiation Protection Ordinance for exemption from regulatory control

    International Nuclear Information System (INIS)

    Birkholz, W.

    2000-01-01

    The system of required radioactivity measurements and limits as well as methods, based on the 10 μSv concept, constitutes the regulatory regime for exemption of radioactive waste materials from regulatory control according to atomic energy law. The methods and administrative procedures are suitable both for smaller amounts of materials, such as those resulting from the use of radioactive substances in scientific research and medical applications, and for the large waste volumes emanating from the dismantling of nuclear installations. The system provided for in the Radiation Protection Ordinance ensures harmonized administrative action of all public authorities involved. (orig./CB) [de

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

    International Nuclear Information System (INIS)

    Szebeni, Janos; Storm, Gert

    2015-01-01

    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.

  2. 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.

  3. Development of Small UAS Beyond-Visual-Line-of-Sight (BVLOS Flight Operations: System Requirements and Procedures

    Directory of Open Access Journals (Sweden)

    Scott Xiang Fang

    2018-04-01

    Full Text Available Due to safety concerns of integrating small unmanned aircraft systems (UAS into non-segregated airspace, aviation authorities have required a set of detect and avoid (DAA systems to be equipped on small UAS for beyond-visual-line-of-sight (BVLOS flight operations in civil airspace. However, the development of small UAS DAA systems also requires BVLOS flights for testing and validation. To mitigate operational risks for small UAS BVLOS flight operations, this paper proposes to initially test small UAS DAA systems in BVLOS flights in a restricted airspace with additional safety features. Later, this paper further discusses the operating procedures and emergency action plans for small UAS BVLOS flight operations. The testing results show that these safety systems developed can help improve operational safety for small UAS BVLOS flight operations.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 39 CFR 230.26 - Do these rules affect the service of process requirements of the Federal Rules of Civil Procedure...

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Do these rules affect the service of process....26 Do these rules affect the service of process requirements of the Federal Rules of Civil Procedure... Rules of Civil Procedure regarding service of process. ...

  9. 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.

  10. 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.

  11. Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

    2015-03-01

    RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

  12. Bioequivalence of a new liquid formulation of benazepril compared with the reference tablet product.

    Science.gov (United States)

    Kelers, K; Devi, J L; Anderson, G A; Zahra, P; Vine, J H; Whittem, T

    2013-08-01

    To compare the bioequivalence and 'switchability' of two formulations of benazepril (tablet and liquid) after oral administration. Randomised cross-over design, followed by parallel comparison. Twelve mixed-breed dogs were administered either a tablet (Group A) or liquid formulation (Group B) of benazepril orally at 0.45 mg/kg daily for 4 days. With no washout period, the dogs then received the alternative treatment at the same dose for a further 4 days. Blood samples taken prior to treatment and serially after treatment were analysed for plasma concentrations of benazepril and benazeprilat and the activity and concentration of angiotensin-converting enzyme (ACE). The calculated percentage inhibition of ACE was defined as the primary outcome variable. No statistically significant differences were found between groups A and B for any variable evaluated. The mean (± SD) percentage of ACE inhibition was 85.5 ± 7.04% for the liquid formulation and 85.9 ± 6.66% for the tablet formulation. The mean of the ratios was 1.00 (80% confidence interval 0.96-1.04). No evaluated effect term (sequence, formulation or period) had any statistical effect on any outcome variable. This study supports a conclusion that, based on pharmacodynamic response, the liquid formulation of benazepril is bioequivalent to the reference tablet formulation. Further, the lack of a sequence effect supports the switchability of these two formulations. © 2013 Australian Veterinary Association.

  13. Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

    Science.gov (United States)

    Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

    2008-10-01

    Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

  14. 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

  15. 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....

  16. 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

  17. 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...

  18. Advantages of automation in plasma sample preparation prior to HPLC/MS/MS quantification: application to the determination of cilazapril and cilazaprilat in a bioequivalence study.

    Science.gov (United States)

    Kolocouri, Filomila; Dotsikas, Yannis; Apostolou, Constantinos; Kousoulos, Constantinos; Soumelas, Georgios-Stefanos; Loukas, Yannis L

    2011-01-01

    An HPLC/MS/MS method characterized by complete automation and high throughput was developed for the determination of cilazapril and its active metabolite cilazaprilat in human plasma. All sample preparation and analysis steps were performed by using 2.2 mL 96 deep-well plates, while robotic liquid handling workstations were utilized for all liquid transfer steps, including liquid-liquid extraction. The whole procedure was very fast compared to a manual procedure with vials and no automation. The method also had a very short chromatographic run time of 1.5 min. Sample analysis was performed by RP-HPLC/MS/MS with positive electrospray ionization using multiple reaction monitoring. The calibration curve was linear in the range of 0.500-300 and 0.250-150 ng/mL for cilazapril and cilazaprilat, respectively. The proposed method was fully validated and proved to be selective, accurate, precise, reproducible, and suitable for the determination of cilazapril and cilazaprilat in human plasma. Therefore, it was applied to a bioequivalence study after per os administration of 2.5 mg tablet formulations of cilazapril.

  19. Bioequivalence study of two losartan tablet formulations with special emphasis on cardiac safety.

    Science.gov (United States)

    Khandave, Suhas S; Sawant, Satish V; Sahane, Rakhi V; Murthi, Vivekanand; Dhanure, Shivanand S; Surve, Pradeep G

    2012-05-01

    To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments. The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters. The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters. The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non

  20. High-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

    Science.gov (United States)

    Inoue, Satoki; Kawaguchi, Masahiko; Sakamoto, Takanori; Kitaguchi, Katsuyasu; Furuya, Hitoshi; Sakaki, Toshisuke

    2002-07-01

    group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group. Amrinone at an infusion rate of 15 or 5 microg x kg(-1) x min(-1) with a reloading at the beginning of rewarming accelerated the rewarming rate of core temperature during deliberate mild hypothermia. This suggests that high-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

  1. Proposing the Use of Partial AUC as an Adjunctive Measure in Establishing Bioequivalence Between Deltoid and Gluteal Administration of Long-Acting Injectable Antipsychotics.

    Science.gov (United States)

    Lee, Lik Hang N; Choi, Charles; Gershkovich, Pavel; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

    2016-12-01

    The maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC) are commonly used to establish bioequivalence between two formulations of the same oral medication. Similarly, these pharmacokinetic parameters have also been used to establish bioequivalence between two sites of administration for the same injectable formulation. However, these conventional methods of establishing bioequivalence are of limited use when comparing modified-release formulations of a drug, particularly those with rates of absorption that are amenable to change with the site of injection. Inherent differences in the rate of absorption can result in clinically significant differences in early exposure and drug response. Here, we propose the use of the partial AUC (pAUC) as a measure of early exposure to aid in the assessment of bioequivalence between the gluteal and the deltoid site of administration for long-acting injectable antipsychotics.

  2. Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

    Science.gov (United States)

    Padgaonkar, K A; Revankar, S N; Bhatt, A D; Vaz, J A; Desai, N D; D'Sa, S; Shah, V; Gandewar, K

    1999-07-01

    To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

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

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Nokyu; Lee, Sungjin [KHNP, Daejeon (Korea, Republic of)

    2015-05-15

    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.

  5. Dissolution efficiency and bioequivalence study using urine data from healthy volunteers: a comparison between two tablet formulations of cephalexin

    Directory of Open Access Journals (Sweden)

    Cristina Helena dos Reis Serra

    2015-06-01

    Full Text Available The aim of the present study was to assess the bioequivalence of two cephalexin tablet formulations available in the Brazilian market (product A as reference formulation and product B as test formulation. Dissolution efficiency (DE% was calculated for both formulations to evaluate their in vitrobiopharmaceutical features. The oral bioequivalence study was performed in twenty-four healthy volunteers in a crossover design. Single oral dose (tablet containing 500 mg of cephalexin of each product was administered with two weeks of washout period. Urinary concentrations of cephalexin were measured by high-performance liquid chromatography (HPLC method and pharmacokinetics parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of cephalexin excreted in the urine, the total amount of cephalexin excreted in the urine and the maximum urinary excretion rate of cephalexin. DE values of immediate-release cephalexin tablets (500 mg were 68.69±4.18% for product A and 71.03±6.63% for product B. Regarding the dissolution test of the two brands (A and B analysed, both were in compliance with the official pharmacopeial specifications, since the dissolution of both formulations was superior to 80% of the amount declared in the label after 45 minutes of test (A=92.09%±1.84; B=92.84%±1.08. The results obtained indicated that the products A and B are pharmaceutical equivalents. Confidence intervals for the pharmacokinetic parameters were in compliance with the international standards, indicating that products A and B can be considered bioequivalents and, therefore, interchangeable.

  6. 48 CFR 622.1503 - Procedures for acquiring end products on the List of Products Requiring Contractor Certification...

    Science.gov (United States)

    2010-10-01

    ... end products on the List of Products Requiring Contractor Certification as to Forced or Indentured... List of Products Requiring Contractor Certification as to Forced or Indentured Child Labor. (e) The... manufacture an end product furnished pursuant to a contract awarded subject to the certification required in...

  7. 48 CFR 22.1503 - Procedures for acquiring end products on the List of Products Requiring Contractor Certification...

    Science.gov (United States)

    2010-10-01

    ... end products on the List of Products Requiring Contractor Certification as to Forced or Indentured... products on the List of Products Requiring Contractor Certification as to Forced or Indentured Child Labor... contracting officer must check the List of Products Requiring Contractor Certification as to Forced or...

  8. Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

    Science.gov (United States)

    Agrawal, S; Kaul, C L; Panchagnula, R

    2001-08-01

    To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

  9. Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

    2013-12-01

    Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

  10. Development of a new benazepril hydrochloride chewable tablet and evaluation of its bioequivalence for treatment of heart failure in dogs.

    Science.gov (United States)

    Qian, M; Chen, T; Zhou, D; Zhang, Z; Zhang, Q; Tang, S; Xiao, X

    2016-02-01

    The aim of the study was to develop a new chewable benazepril hydrochloride(BH) tablet, investigate its physical properties, and evaluate its bioequivalence with the branded formulation (Fortekor). A corrective agent was included in the formula to improve its palatability and convenience for administration to dogs. The tablet remained stable in light, heat, and humidity tests, and its physical properties such as hardness, uniformity of content, and dissolution rate were highly consistent with the technical standards. After single and repeated administrations to eight beagles and single dose to 14 mongrel dogs (0.5 mg/kg p.o.), plasma BH and its active metabolite, benazeprilat (BZ), were detected. There was no significant difference in the major pharmacokinetic parameters (Cmax , Tmax, and AUC₀₋₂₄) between the two formulations. The 90% confidence intervals calculated for the ratios of area under the time-concentration curve (AUC₀₋₂₄) were 92.4-116.3% for BH and 89.9-102.3% for BZ, within the accepted range for bioequivalence of 80-125%. The results showed our new chewable tablet is bioequivalent to the commercial product and suitable for addition to the benazepril product family for the treatment of heart failure in dogs. © 2015 John Wiley & Sons Ltd.

  11. 29 CFR 1928.52 - Protective frames for wheel-type agricultural tractors-test procedures and performance requirements.

    Science.gov (United States)

    2010-07-01

    ... a 4,410-lb (2,000-kg) weight acting as a pendulum. The impact face of the weight shall be 27 ± 1 in..., or blocking shift or break during the test, the test shall be repeated. (ii) H = Vertical height of... test procedure; and (C) Impact at side. The blocking and restraining shall conform to paragraphs (d)(3...

  12. 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

  13. 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.

  14. Effect of the Wetting Agent Sodium Lauryl Sulfate on the Pharmacokinetics of Alectinib: Results From a Bioequivalence Study in Healthy Subjects.

    Science.gov (United States)

    Morcos, Peter N; Parrott, Neil; Banken, Ludger; Timpe, Carsten; Lindenberg, Marc; Guerini, Elena; Dall, Georgina; Bogman, Katrijn; Sturm, Carolina; Zeaiter, Ali; Martin-Facklam, Meret; Phipps, Alex

    2017-05-01

    The anaplastic lymphoma kinase (ALK) inhibitor alectinib is an effective treatment for ALK-positive non-small-cell lung cancer. This bioequivalence study evaluated the in vivo performance of test 3 formulations with the reduced wetting agent sodium lauryl sulfate (SLS) content. This randomized, 4-period, 4-sequence, crossover study compared alectinib (600 mg) as 25%, 12.5%, and 3% SLS hard capsule formulations with the reference 50% SLS clinical formulation in healthy subjects under fasted conditions (n = 49), and following a high-fat meal (n = 48). Geometric mean ratios and 90% confidence intervals (CIs) for C max , AUC 0-last , and AUC 0-∞ of alectinib, its major active metabolite, M4, and alectinib plus M4 were determined for the test formulations versus the reference formulation. Bioequivalence was concluded if the 90%CIs were within the 80% to 125% boundaries. The 25% SLS formulation demonstrated bioequivalence to the reference 50% SLS formulation for C max , AUC 0-last , and AUC 0-∞ of alectinib, M4, and alectinib plus M4 under both fasted and fed conditions. Further reductions in SLS content (12.5% and 3% SLS) did not meet the bioequivalence criteria. Cross-group comparisons showed an approximately 3-fold positive food effect. Reducing SLS to 25% resulted in a formulation that is bioequivalent to the current 50% SLS formulation used in alectinib pivotal trials. © 2016, The American College of Clinical Pharmacology.

  15. Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

    Science.gov (United States)

    Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

    2016-07-01

    Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Significance of metabolites in bioequivalence: losartan potassium as a case study.

    Science.gov (United States)

    Charoo, Naseem Ahmad; Cristofoletti, Rodrigo; Khatri, Aamer Roshanali; Ali, Areeg Anwer

    2014-06-01

    Estimation of metabolite data as a supportive evidence of comparable therapeutic outcome is recommended by various guidance documents. However, a consensus on using it solely to establish bioequivalence (BE) is lacking as parent drug is believed to detect pharmacokinetic differences between test and reference formulations better. Four BE studies of losartan potassium reported in the literature are reviewed. In all the four studies, 90% confidence intervals (CIs) of geometric mean ratios of the test and reference formulations for maximum blood drug concentration (Cmax ) of losartan potassium were outside the acceptable range of 80%-125%, whereas, 90% CIs for its active metabolite, losartan carboxylic acid (LCA), were within the acceptance criteria. Although BE with respect to area under the plasma concentration versus time profile curve was demonstrated in all the cases, BE with respect to Cmax could not be established. However, marketing authorization in all the four cases was granted based on scientific evidence that LCA is 10-40 times more potent than losartan, LCA exhibited higher plasma concentration levels than losartan, pharmacodynamic effects correlate with LCA, and losartan shows wide therapeutic index. Further, widened CI limits for losartan were accepted. Losartan presents an opportunity in the diligence of the principles of quality risk management for selecting moiety on which BE decision must be based. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Investigation of Bioequivalence Between Brand-name and Generic Irinotecan Products.

    Science.gov (United States)

    Saito, Ken-Ichi; Inoue, Yutaka; Ikegami, Yoji; Nanbo, Izumi; Onozuka, Mari; Sano, Kazumi; Yoshida, Hisahiro; Sakamoto, Toshihiro; Tatebayashi, Emi; Fujita, Ken-Ichi; Sasaki, Yasutsuna; Kitazawa, Takaki

    2016-11-01

    To investigate bioequivalence among generic and brand-name irinotecan products. Products of Yakult and Daiichi-Sankyo (brand-name products), Sandoz, Nippon Kayaku, Taiho, and Sawai were compared with respect to their composition and antitumor activity. High-performance liquid chromatography demonstrated that related substances were within the acceptable range. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed significant differences in cytotoxicity for four cancer cell lines among the products. The concentration of the active compound SN-38 was highest in Yakult's product (23.82 ng/ml) and lowest in Daiichi-Sankyo's product (8.96 ng/ml). MTT assay data were correlated with the SN-38 concentration, suggesting that it influenced differences in cytocidal activity among products. However, the SN-38 concentration was far lower than that of irinotecan (20 mg/ml), suggesting a negligible clinical effect. Metabolism of irinotecan to SN-38 or open-ring forms did not differ significantly among the products. The generic products showed equivalent efficacy and safety to the brand-name products. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

    Science.gov (United States)

    Agrawal, S; Singh, I; Kaur, K J; Bhade, S R; Kaul, C L; Panchagnula, R

    2002-10-01

    Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

  19. Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w).

    Science.gov (United States)

    Mitra, Amitava; Kim, Nanhye; Spark, Darren; Toner, Frank; Craig, Susan; Roper, Clive; Meyer, Thomas A

    2016-12-01

    The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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.

  1. 18 CFR 376.209 - Procedures during periods of emergency requiring activation of the Continuity of Operations Plan.

    Science.gov (United States)

    2010-04-01

    ... periods of emergency requiring activation of the Continuity of Operations Plan. 376.209 Section 376.209... of the Continuity of Operations Plan. (a)(1) The Commission's Continuity of Operations Plan is...) During periods when the Continuity of Operations Plan is activated, the Commission will continue to act...

  2. 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

    2018-06-01

    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.
.

  3. 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.
.

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

    Science.gov (United States)

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

    2017-08-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Mona Zarifpour

    2017-05-01

    Full Text Available 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 T2-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. Pharmacokinetic and bioequivalence study of two brands of valsartan tablets in healthy male volunteers.

    Science.gov (United States)

    Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba; Nemati, Mahboob

    2010-01-01

    Valsartan (CAS 137862-53-4) is an antihypertensive drug belonging to the family of angiotensin II receptor antagonists acting at the AT1 receptor, which mediates all known effects of angiotensin II on the cardiovascular system. In the present study, the pharmacokinetic parameters of two oral formulations of valsartan tablets were compared in a randomized, single oral dose, two-treatment crossover design in 24 healthy male volunteers under fasting conditions. After an overnight fast, the volunteers received 80 mg valsartan. Blood samples were collected up to 48 h and drug concentrations were determined by a reverse-phase HPLC method with fluorescence detection. Various pharmacokinetic parameters were determined from the plasma concentration-time curves of both formulations. The obtained values for test and reference products were 3067.7 +/- 1,281.7 and 3,304.3 +/- 1,196.4 ng/ml for Cmax; 17,834.4 +/- 7,083.8 and 18,319.1 +/- 7,800.7 ng x h/ml for AUC0-48; 18,825.7 +/- 7,553.2 and 19,172.2 +/- 8,307.2 ng x h/ml for AUC0-infinity, respectively. The 90% confidence intervals obtained by analysis of variance were 86.84-100.87% for Cmax and 93.43-115.54% for AUC0-t, which are within the acceptance range of 80-125%. Therefore it can be concluded that both products are bioequivalent in terms of rate and extent of drug absorption and therefore interchangeable.

  8. 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.

  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. 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.

  11. 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.
.

  12. 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.

  13. 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.

  14. 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

  15. Emergency procedures

    International Nuclear Information System (INIS)

    Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail

    2004-01-01

    The following subjects are discussed - Emergency Procedures: emergency equipment, emergency procedures; emergency procedure involving X-Ray equipment; emergency procedure involving radioactive sources

  16. Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment.

    Science.gov (United States)

    Oishi, Masayo; Chiba, Koji; Fukushima, Takashi; Tomono, Yoshiro; Suwa, Toshio

    2012-01-01

    In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be ≥80% despite AUClast/AUCinf being AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug.

  17. Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid.

    Science.gov (United States)

    Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival

    2015-07-10

    The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis-Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this model by comparing the results obtained in NONMEM simulations with published experimental data at a dose of 1000 mg. The validated model was used to simulate bioequivalence trials at 3 dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h (-1)). Finally, the third aim was to determine which analyte (parent drug, first generation or second generation metabolite) was more sensitive to changes in formulation performance. The validation results showed that the concentration-time curves obtained with the simulations reproduced closely the published experimental data, confirming model performance. The parent drug (ASA) was the analyte that showed to be more sensitive to the decrease in pharmaceutical quality, with the highest decrease in Cmax and AUC ratio between test and reference formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System

    Science.gov (United States)

    Ramirez, Elena; Laosa, Olga; Guerra, Pedro; Duque, Blanca; Mosquera, Beatriz; Borobia, Alberto M; Lei, Suhua H; Carcas, Antonio J; Frias, Jesus

    2010-01-01

    AIM The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes. METHODS We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products. RESULTS Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3. CONCLUSIONS Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for Cmax or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies. PMID:21039763

  19. [A survey carried out among Italian physicians regarding non-required clinical examinations, treatments and procedures in the current clinical practice: results and considerations.

    Science.gov (United States)

    Vernero, Sandra; Giustetto, Guido

    2017-01-01

    A survey addressed to all Italian physicians regarding how they behave when a patient asks them to prescribe non-required clinical examinations, treatments and procedures has been carried out for the first time. The survey - realized during the last months of the year 2015 thanks to the collaboration between Slow Medicine and the National Federation of Associations of Doctors, Surgeons and Dentists - is based on a questionnaire given to the America physicians by the ABIM Foundation in 2014. The Italian survey results cannot be compared with the American ones because different approaches were used. 4,263 physicians started to fill in the questionnaire and 3,688 completed it. The results suggest that the physicians that answered the questions are highly aware of the over-usage of diagnostic tests and treatments, and among the main reasons they cite the need of safety and then the fear of legal consequences. Most of the physicians who answered the questions believe to be responsible for giving patients accurate information in order to avoid non-required practices, and that the physician is the right person with the most suitable role to face the problem. Among the most important and useful tools to reduce the prescription of non-required examinations and treatments, physicians indicate the possibility to have much more time available to discuss the different options with their patients, to arrange the evidence-based information material for the patients, and to explain the reform on the physician's responsibility (recently approved as law). Therefore, it stands out the opportunity to apply provisions aimed at providing the patients with more accurate information and at improving the relationship between the physician and the patient by ensuring on the one hand more availability of dedicated time and on the other hand the training of the physicians on scientific topics as well as on topics concerning communication and shared decisions. The communication can be

  20. 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.

  1. 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.

  2. 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.

  3. Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

    Science.gov (United States)

    Mylonas, Konstantinos S; Reinhorn, Michael; Ott, Lauren R; Westfal, Maggie L; Masiakos, Peter T

    2017-11-01

    A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P require any opioid analgesics, and nearly all of those who thought that they did need opioids used reserved.

  4. 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

  5. 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

  6. 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.

  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. Determination of itopride in human plasma by liquid chromatography coupled to tandem mass spectrometric detection: application to a bioequivalence study.

    Science.gov (United States)

    Lee, Heon-Woo; Seo, Ji-Hyung; Choi, Seung-Ki; Lee, Kyung-Tae

    2007-01-30

    A simple method using a one-step liquid-liquid extraction (LLE) with butyl acetate followed by high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the determination of itopride in human plasma, using sulpiride as an internal standard (IS). Acquisition was performed in multiple reaction monitoring (MRM) mode, by monitoring the transitions: m/z 359.5>166.1 for itopride and m/z 342.3>111.6 for IS, respectively. Analytes were chromatographed on an YMC C18 reverse-phase chromatographic column by isocratic elution with 1 mM ammonium acetate buffer-methanol (20: 80, v/v; pH 4.0 adjusted with acetic acid). Results were linear (r2=0.9999) over the studied range (0.5-1000 ng mL(-1)) with a total analysis time per run of 2 min for LC-MS/MS. The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

  9. Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study.

    Science.gov (United States)

    Ma, Jing; Yuan, Li-Hua; Ding, Mei-Juan; Zhang, Jun; Zhang, Qing; Xu, Qun-Wei; Zhou, Xue-Min

    2009-03-01

    A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

  10. 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%.

  11. 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.

  12. 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.

  13. Competence and lastingness in specialized clinical laboratories: technical report about requirements concerning quality of users competence and used processes in immunochemical diagnostic procedures using isotopic and non-isotopic tracer technologies

    International Nuclear Information System (INIS)

    Wiegel, B.

    2005-01-01

    From the citizens view this technical report about immunochemical diagnostic procedures using radioactive and nonradioactive tracer technologies describes the requirements in special laboratory diagnostics concerning competency and process control. Governmental or administrational obligations of inspecting both skill and sites to guarantee patients security are pointed out. (orig.)

  14. 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…

  15. Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

    Science.gov (United States)

    Mita, Sachiko; Chitnis, Shripad D; Kulmatycki, Kenneth; Salunke, Atish; He, Yan-Ling; Zhou, Wei; Suzuki, Hikoe

    2016-04-01

    To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for vildagliptin and metformin. In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.

  16. 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.

  17. 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.

  18. Bioequivalence of 250 mg lysine clonixinate tablets after a single oral dose in a healthy female Mexican population under fasting conditions.

    Science.gov (United States)

    Marcelín-Jiménez, G; Angeles, A C P; García, A; Morales, M; Rivera, L; Martín-Del-Campo, A

    2010-05-01

    To evaluate the bioequivalence between two 250 mg-tablets of lysine clonixinate, Dorixina Forte (Siegfried Rhein, México) as reference product, and Prestodol (Farmaceúticos Rayere, S.A., México) as test formulation. 26 healthy adult female Mexican volunteers received a single oral dose of 250-mg lysine clonixinate under fasting conditions. The drug was administered following a randomized, two-period, two-sequence, cross-over design. Twelve serial blood samples were collected up to 8 h after dosing, and clonixin (CLX) was measured by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Decimal logarithm values of Cmax and area under the curve (AUC) were used to construct a classic confidence interval at 90% (90% CI). Bioequivalence was established if 90% CI of mean ratios (test/reference) fall within the 0.8-1.25 range. Volunteers formed a homogeneous population in terms of age (27.2 +/- 6.3 years), weight (55.9 +/- 6.5 kg), height (1.6 +/- 0.04 m), and body mass index (BMI) (22.91 +/- 2.03 kg/m(2)). Reference formulation exhibited the following pharmacokinetics: C(max) (32.39 +/- 8.32 microg/ml); t(max) (0.64 +/- 0.2 h); AUC0-8h (48.92 +/- 16.51 microg x h/ml); t1/2 (1.3 +/- 0.24 h); CLapp (5.64 +/- 1.99 l/h), and Vdapp (10.22 +/- 2.9 l). Concerning bioequivalence, 90% CI were: C(max) (82.32 - 98.79), AUC0-t (94.59-106.29), and AUC(0-inf) (94.61-106.42), with a statistical power of > 0.90 at every tested interval. This single-dose study found that both 250-mg immediate-release tablets of lysine clonixinate met the Mexican regulatory criteria for bioequivalence in these volunteers.

  19. 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.

  20. 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.

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  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. Procedural sedation analgesia

    OpenAIRE

    Sheta, Saad A

    2010-01-01

    The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Individualized care is important when determining if a patient requires procedural sedation analgesia (PSA). The patient might need an anti-anxiety drug, pain medicine, immobilization, simple reassurance, or a combination of these interve...

  7. 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

  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

    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

  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

    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

  10. 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

  11. Federal Student Loan Programs: Opportunities Exist to Improve Audit Requirements and Oversight Procedures. Report to Congressional Committees. GAO-10-668

    Science.gov (United States)

    Daly, Kay L.

    2010-01-01

    The Higher Education Opportunity Act of 2008, Pub. L. No. 110-315, mandated GAO (Government Accountability Office) to study the financial and compliance audits and reviews required or conducted for the Federal Family Education Loan (FFEL) program and the Federal Direct Student Loan (DL) program. The Department of Education's (Education) Office of…

  12. Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

    Science.gov (United States)

    Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

    2015-12-07

    In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for

  13. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date. Final rule; delay of effective date.

    Science.gov (United States)

    2004-02-23

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2006, the effective date of certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). In the Federal Register of May 3, 2000 (65 FR 25639), the agency delayed until October 1, 2001, the effective date of certain requirements in the final rule relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record, and distribution of blood derivatives by entities that meet the definition of a "health care entity" in the final rule. The agency further delayed the effective date of these requirements in three subsequent Federal Register notices. Most recently, in the Federal Register of January 31, 2003 (68 FR 4912), FDA delayed the effective date until April 1, 2004. This action further delays the effective date of these requirements until December 1, 2006. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The agency is taking this action to address concerns about the requirements in the final rule raised by affected parties. As explained in the SUPPLEMENTARY INFORMATION section, FDA is working with stakeholders through its counterfeit drug initiative to facilitate widespread, voluntary adoption of track and trace technologies that will generate a de facto electronic pedigree, including prior transaction history back to the original manufacturer, as a routine course of business. If this technology is widely adopted, it is expected to help fulfill the pedigree requirements of the PDMA and obviate or resolve many of the concerns that have been raised with respect to the final rule by ensuring that an electronic pedigree travels with a drug product at all times. Therefore, it is necessary to delay the effective date of Sec

  14. Pretreatment procedures

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    It is frequently in the patient's best interest that radiation treatments are initiated soon after the decision to treat is made. However, it is essential to good radiation therapy that the patient's treatment course be planned and beam-modifying devices be fabricated with utmost care prior to treatment. The objectives of the treatment, along with the treatment parameters and techniques necessary to achieve these objectives, must be discussed prior to initiating planning procedures. Determination of the target volume is made by the radiation oncologist; this is based on knowledge of the history of the tumor, the patterns of spread of the disease, and on diagnostic findings during the work-up of each patient. It is then necessary to obtain several measurements of the patient and also to identify the position of the target volume and of adjacent normal organs with respect to known external skin marks before the actual treatment planning is begun. Such localization can be done through several methods. The two most commonly used methods are radiographic and computed tomography (CT), both of which are discussed in this chapter. The measurements often include contours of the patient's external surface, usually in the axial plane of the central axis of the beam, and often in multiple levels within the region to be treated. Three dimensional localization and treatment planning requires thorough understanding of geometry as well as of patient positioning and immobilization. This chapter attempts to clarify some of these complicated but essential preparations for treatment

  15. Automation of the testing procedure

    International Nuclear Information System (INIS)

    Haas, H.; Fleischer, M.; Bachner, E.

    1979-01-01

    For the judgement of technologies applied and the testing of specific components of the HTR primary circuit, complex test procedures and data evaluations are required. Extensive automation of these test procedures is indispensable. (orig.) [de

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Development and validation of a liquid chromatography-tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study.

    Science.gov (United States)

    Ye, Ling; Shi, Jian; Wan, Shanhe; Yang, Xiaoshan; Wang, Ying; Zhang, Jiajie; Zheng, Dayong; Liu, Zhongqiu

    2013-11-01

    Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

  1. 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

  2. Quantification of sibutramine and its two metabolites in human plasma by LC–ESI-MS/MS and its application in a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Venkata Suresh Ponnuru

    2012-08-01

    Full Text Available Obesity can be considered as a chronic illness of epidemic proportion and its incidents have increased exponentially in recent years. The use of anti-obesity drugs such as sibutramine is somewhat helpful. There is a need to quantify such drugs in biological samples, which is generally quite difficult. In this report, we developed and validated a simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS method for the quantification of sibutramine (SB and its two metabolites N-des methyl sibutramine (DSB and N-di desmethyl sibutramine (DDSB in human plasma. Zorbax SB-C18 (4.6 mm×75 mm, 3.5 μm, 80 Å analytical column and 5 mM ammonium formate:acetonitrile (10:90, v/v mobile phase were used for chromatographic separation of SB, DSB and DDSB. Multiple reaction monitoring (MRM in the positive mode was used to detect SB, DSB and DDSB at m/z 280.3/124.9, 266.3/125.3 and 252.2/124.9, respectively. Liquid–liquid extraction was used for the extraction of analytes and internal standard from human plasma. This method was validated over a linear concentration range of 10.0–10,000.0 pg/mL for SB, DSB and DDSB with correlation coefficients (r of ≥0.9997. The drug and the two metabolites were stable in plasma samples. The validated method was successfully applied in a bioequivalence and pharmacokinetic study with human volunteers under fasting condition. Keywords: LC–ESI-MS/MS, Sibutramine, Human plasma, Bioequivalence, Pharmacokinetic study

  3. 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

  4. 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...

  5. 12 CFR 574.6 - Procedural requirements.

    Science.gov (United States)

    2010-01-01

    ... will commence upon receipt by the Office of a notice or application deemed sufficient under paragraph... commence again in its entirety upon receipt of such additional information. (i) The 60-day period for the... Information Act to such information for reasons of personal privacy or business confidentiality, which shall...

  6. Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

    Science.gov (United States)

    Brendel, Erich; Weimann, Boris; Dietrich, Hartmut; Froede, Christoph; Thomas, Dirk

    2013-09-01

    To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs. 49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days. Plasma samples were collected for 48 hours after dosing and assayed using a validated LC-MS/MS method. Bioequivalence between the FDC and the loose combination as well as the impact of combined treatment with both drugs on candesartan pharmacokinetics was evaluated in 47 subjects, while the corresponding impact of treatment with both drugs on nifedipine pharmacokinetics was assessed in 46 patients. For AUC(0-tlast) and Cmax the 90% confidence intervals (CIs) for the ratios of the FDC vs. the corresponding loose combination were within the acceptance range for bioequivalence of 80 - 125%. When comparing AUC(0-tlast) and Cmax of nifedipine and candesartan after dosing with the loose combination vs. each drug alone, the 90% CIs remained within the range of 80 - 125% indicating the absence of a clinically relevant pharmacokinetic drug-drug interaction. Nifedipine and candesartan as well as the combinations were well tolerated. The FDC containing 60 mg nifedipine and 32 mg candesartan was bioequivalent to the corresponding loose combination following single oral doses under fasting conditions. No clinically relevant pharmacokinetic drug-drug interaction between nifedipine and candesartan was observed.

  7. 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)

    OpenAIRE

    Stavchansky, Salomon

    2008-01-01

    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 ...

  8. 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

  9. Procedural sedation analgesia

    Directory of Open Access Journals (Sweden)

    Sheta Saad

    2010-01-01

    Full Text Available The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Individualized care is important when determining if a patient requires procedural sedation analgesia (PSA. The patient might need an anti-anxiety drug, pain medicine, immobilization, simple reassurance, or a combination of these interventions. The goals of PSA in four different multidisciplinary practices namely; emergency, dentistry, radiology and gastrointestinal endoscopy are discussed in this review article. Some procedures are painful, others painless. Therefore, goals of PSA vary widely. Sedation management can range from minimal sedation, to the extent of minimal anesthesia. Procedural sedation in emergency department (ED usually requires combinations of multiple agents to reach desired effects of analgesia plus anxiolysis. However, in dental practice, moderate sedation analgesia (known to the dentists as conscious sedation is usually what is required. It is usually most effective with the combined use of local anesthesia. The mainstay of success for painless imaging is absolute immobility. Immobility can be achieved by deep sedation or minimal anesthesia. On the other hand, moderate sedation, deep sedation, minimal anesthesia and conventional general anesthesia can be all utilized for management of gastrointestinal endoscopy.

  10. 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

  11. 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

  12. 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.)

  13. 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...

  14. Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

    Science.gov (United States)

    Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

    2002-02-21

    Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

  15. Quantification of amlodipine and atorvastatin in human plasma by UPLC-MS/MS method and its application to a bioequivalence study.

    Science.gov (United States)

    Rezk, Mamdouh R; Badr, Kamal A

    2018-07-01

    A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C 18 (50 × 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Liquid chromatography-tandem mass spectrometry for the quantification of flurbiprofen in human plasma and its application in a study of bioequivalence.

    Science.gov (United States)

    Mei, Chenghan; Li, Bin; Yin, Qiangfeng; Jin, Jing; Xiong, Ting; He, Wenjuan; Gao, Xiujuan; Xu, Rong; Zhou, Piqi; Zheng, Heng; Chen, Hui

    2015-07-01

    A simple, quick and accurate LC-MS/MS method for the quantification of flurbiprofen in human plasma with indomethacin as internal standard (IS) was developed and validated. Samples were treated with methanol to precipitate proteins, then separated on a Ultimate C18 column (5μm, 2.1×50mm) with a gradient elusion process. Mobile phase A was comprised of water and formic acid, mobile phase B was comprised of acetonitrile and formic acid. Multi reaction monitoring (MRM) signals were saved on a negative ionization electrospray mass spectrometer. The calibration curve showed good linearity in the range of 40.00-10000.00μg/L (r(2)=0.998). Intra-day RE was 0.2-2.2%. Inter-day RE was 0.5-3.4%. The samples showed good stability under the study conditions. No significant matrix effect was observed. The established method was then applied to a bioequivalence study of a flurbiprofen axetil formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 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.

  18. Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

    Science.gov (United States)

    Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

    2011-12-15

    A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. 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.

  20. [Costing nuclear medicine diagnostic procedures].

    Science.gov (United States)

    Markou, Pavlos

    2005-01-01

    To the Editor: Referring to a recent special report about the cost analysis of twenty-nine nuclear medicine procedures, I would like to clarify some basic aspects for determining costs of nuclear medicine procedure with various costing methodologies. Activity Based Costing (ABC) method, is a new approach in imaging services costing that can provide the most accurate cost data, but is difficult to perform in nuclear medicine diagnostic procedures. That is because ABC requires determining and analyzing all direct and indirect costs of each procedure, according all its activities. Traditional costing methods, like those for estimating incomes and expenses per procedure or fixed and variable costs per procedure, which are widely used in break-even point analysis and the method of ratio-of-costs-to-charges per procedure may be easily performed in nuclear medicine departments, to evaluate the variability and differences between costs and reimbursement - charges.

  1. FFTF reactor plant procedures plan

    International Nuclear Information System (INIS)

    1972-01-01

    The document presented defines the plan to be used to coordinate the preparation, review, approval, and issuance of the operating procedure documents required to ensure safe and efficient operation of FFTF

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Determination of ergocalciferol in human plasma after Diels-Alder derivatization by LC–MS/MS and its application to a bioequivalence study

    Directory of Open Access Journals (Sweden)

    Pritesh Contractor

    2017-12-01

    Full Text Available An accurate, sensitive and selective method is developed for determination of ergocalciferol (vitamin D2 in human plasma using LC–MS/MS. After liquid-liquid extraction with n-hexane, ergocalciferol was derivatized by reacting with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD, a strong dienophile based on Diels-Alder reaction. Ergocalciferol and its deuterated internal standard, ergocalciferol-d6, were analyzed on X Select CSH C18 (100 mm×4.6 mm, 2.5 µm column using acetonitrile and 0.1% (v/v formic acid in water containing 0.14% methylamine within 6.0 min under gradient elution mode. Tandem mass spectrometry in positive ionization mode was used to quantify ergocalciferol by multiple reaction monitoring (MRM. Entire data processing was done using Watson LIMS™ software which provided excellent data integrity and high throughput with improved operational efficiency. The major advantage of this method includes higher sensitivity (0.10 ng/mL, superior extraction efficiency (≥83% and small sample volume (100 µL for processing. The method was linear in the concentration range of 0.10–100 ng/mL for ergocalciferol. The intra-batch and inter-batch accuracy and precision (% CV values varied from 97.3% to 109.0% and 1.01% to 5.16%, respectively. The method was successfully applied to support a bioequivalence study of 1.25 mg ergocalciferol capsules in 12 healthy subjects. Keywords: Ergocalciferol, Diels-Alder reaction, 4-phenyl-1,2,4-triazoline-3,5-dione, LC–MS/MS, Human plasma

  8. Quantitation of itopride in human serum by high-performance liquid chromatography with fluorescence detection and its application to a bioequivalence study.

    Science.gov (United States)

    Singh, Sonu Sundd; Jain, Manish; Sharma, Kuldeep; Shah, Bhavin; Vyas, Meghna; Thakkar, Purav; Shah, Ruchy; Singh, Shriprakash; Lohray, Brajbhushan

    2005-04-25

    A new method was developed for determination of itopride in human serum by reversed phase high-performance liquid chromatography (HPLC) with fluorescence detection (excitation at 291 nm and emission at 342 nm). The method employed one-step extraction of itopride from serum matrix with a mixture of tert-butyl methyl ether and dichloromethane (70:30, v/v) using etoricoxib as an internal standard. Chromatographic separation was obtained within 12.0 min using a reverse phase YMC-Pack AM ODS column (250 mm x 4.6 mm, 5 microm) and an isocratic mobile phase constituting of a mixture of 0.05% tri-fluoro acetic acid in water and acetonitrile (75:25, v/v) flowing at a flow rate of 1.0 ml/min. The method was linear in the range of 14.0 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 14.0 ng/ml. Average recovery of itopride and the internal standard from the biological matrix was more than 66.04 and 64.57%, respectively. The inter-day accuracy of the drug containing serum samples was more than 97.81% with a precision of 2.31-3.68%. The intra-day accuracy was 96.91% or more with a precision of 5.17-9.50%. Serum samples containing itopride were stable for 180.0 days at -70+/-5 degrees C and for 24.0 h at ambient temperature (25+/-5 degrees C). The method was successfully applied to the bioequivalence study of itopride in healthy, male human subjects.

  9. 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.

  10. Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies.

    Science.gov (United States)

    Xu, Beibei; Yang, Guanyi; Ge, Shufan; Yin, Taijun; Hu, Ming; Gao, Song

    2013-11-01

    The purpose of this study is to develop an UPLC-MS/MS method to quantify 3-hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG) from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1% formic acid in water as mobile phases. The mass analysis was performed in an API 5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The one-step protein precipitation by acetonitrile was used to extract the analytes from blood. The results showed that the linear response range was 0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than 15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than 20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%, accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10 μl of blood is needed due to the high sensitivity of this method. The validated method was successfully used to pharmacokinetic study in A/J mouse, transport study in the Caco-2 cell culture model, and glucuronidation study using mice liver and intestine microsomes. The applications revealed that this method can be used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers such HBSS and KPI. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Multiple position borehole extensometer procedure: Final draft

    International Nuclear Information System (INIS)

    1986-08-01

    The purpose of the Multiple Position Borehole Extensometer Procedure is to provide detailed information for MPBXs installed at the salt Deaf Smith County ESF. This procedure includes design of equipment, installation, instructions, instrument locations, measurement requirements, support requirements, quality assurance procedures, and data acquisition requirements. Data reduction procedures are also discussed; however, the relevance of the data is discussed elsewhere in the appropriate test plans. Sufficient detail is provided in this procedure to allow for integrating the requirements of this procedure into both the facility construction and overall underground testing programs; identifying necessary equipment for procurement; determining data acquisition requirements as input to Automatic Data Acquisition System (ADAS) design; providing step-by-step procedures for training personnel as well as for directing field operations; establishing quality assurance (QA) checkpoints and implementation methods; and defining data reduction methods and providing the anticipated accuracy of the system. 11 refs., 14 figs

  12. Subsea HIPPS design procedure

    International Nuclear Information System (INIS)

    Aaroe, R.; Lund, B.F.; Onshus, T.

    1995-01-01

    The paper is based on a feasibility study investigating the possibilities of using a HIPPS (High Integrity Pressure Protection System) to protect a subsea pipeline that is not rated for full wellhead shut-in pressure. The study was called the Subsea OPPS Feasibility Study, and was performed by SINTEF, Norway. Here, OPPS is an acronym for Overpressure Pipeline Protection System. A design procedure for a subsea HIPPS is described, based on the experience and knowledge gained through the ''Subsea OPPS Feasibility Study''. Before a subsea HIPPS can be applied, its technical feasibility, reliability and profitability must be demonstrated. The subsea HIPPS design procedure will help to organize and plan the design activities both with respect to development and verification of a subsea HIPPS. The paper also gives examples of how some of the discussed design steps were performed in the Subsea OPPS Feasibility Study. Finally, further work required to apply a subsea HIPPS is discussed

  13. 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.

  14. 32 CFR 635.35 - Procedures.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Procedures. 635.35 Section 635.35 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS LAW ENFORCEMENT REPORTING Victim and Witness Assistance Procedures § 635.35 Procedures. (a) As required by Federal law, Army personnel...

  15. 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

  16. MITS Feed and Withdrawal Subsystem: operating procedures

    International Nuclear Information System (INIS)

    Brown, W.S.

    1980-01-01

    This procedure details the steps required to provide continuous feed flow and withdrawal of process product and waste flows in support of thruput operation in the cascade or its elements. It particularly requires operator attention to safety considerations

  17. Procedure for taking physical inventories

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    This session is intended to apprise one of the various aspects of procedures and routines that Exxon Nuclear uses with respect to its nuclear materials physical inventory program. The presentation describes how plant physical inventories are planned and taken. The description includes the planning and preparation for taking the inventory, the clean-out procedures for converting in-process material to measurable items, the administrative procedures for establishing independent inventory teams and for inventorying each inventory area, the verification procedures used to include previously measured tamper-safed items in the inventory, and lastly, procedures used to reconcile the inventory and calculate MUF (materials unaccounted for). The purpose of the session is to enable participants to: (1) understand the planning and pre-inventorty procedures and their importance; (2) understand the need for and the required intensity of clean-out procedures; (3) understand how inventory teams are formed, and how the inventory is conducted; (4) understand the distinction between inventory previously measured tamper-safed items and other materials not so characterized; (5) understand the reconciliation procedures; and (6) calculate a MUF given the book and inventory results

  18. 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

  19. CT4 - Cost-Optimum Procedures

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    This report collects the status in European member states regarding implementation of the cos optimum procedure for setting energy performance requirements to new and existing buildings.......This report collects the status in European member states regarding implementation of the cos optimum procedure for setting energy performance requirements to new and existing buildings....

  20. HASL procedures manual

    International Nuclear Information System (INIS)

    Harley, J.H.

    1977-08-01

    Additions and corrections to the following sections of the HASL Procedures Manual are provided: General, Sampling, Field Measurements; General Analytical Chemistry, Chemical Procedures, Data Section, and Specifications

  1. 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

  2. Estudio de bioequivalencia: formulaciones genéricas y comerciales de estaduvine, lamiduvine, zidovudine e indinavir en pacientes cubanos infectados con VIH Bioequivalence study: generic and trade formulations of stavudine, lamivudine, zidovudine and indinavir in Cuban HIV-infected subjects

    Directory of Open Access Journals (Sweden)

    Alicia Tarinas Reyes

    2006-08-01

    Full Text Available Objetivo: El presente estudio describe los estudios de bioequivalencia de los genéricos cubanos antirretrovirales estavudina, lamivudina, zidovudina e indinavir con respecto a sus productos innovadores. Diseño: Los estudios de bioequivalencia de cada antirretroviral estudiado (formulación de prueba, P y referencia, R, se realizaron en 13 ó 14 sujetos, según el caso con la utilización de las medias en un estudio aleatorio, cruzado y a dosis única con un período de lavado de 10 días. Métodos: Las concentración de los antirretrovirales en plasma se monitorearon durante un período de 12 h después de la administración de estos, mediante el uso de métodos validados de cromatografía líquida de alta resolución (HPLC. Los parámetros farmacocinéticos se determinaron con el uso el software profesional WinNolin, versión 2.1. La comparación de los parámetros farmacocinéticos se realizó con un intervalo de confianza del 95 % con la utilización del software NCSS 2000 PASS 2000 (hipótesis nula. Para el estudio de bioequivalencia se usó el software Equiv Test de soluciones estadísticas, empleando ANOVA con el 90 % de intervalo de confianza. Resultados: El presente estudio mostró que no se observaron diferencias significativas en las medias de AUC0-12, AUC0-¥, Cmax y Tmax de ambas formulaciones de estavudina, lamivudina, zidovudina e indinavir. Se concluye que los parámetros farmacocinéticos estudiados se encuentran dentro de los rangos establecidos siendo 80-125 % para Cmax, AUC0-12, y AUC0-¥. En el caso de Cmax de la zidovudina el rango fue 70-143 %. Conclusión: Estos resultados avalan que los genéricos antirretrovirales cubanos son bioequivalentes con sus respectivos productos innovadores en términos de velocidad y magnitud de la absorciónObjective: The present study describes the determination of the bioequivalence of the Cuban generic and trade formulations of stavudine, lamivudine, zidovudine, and indinavir. Design: The

  3. 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

  4. 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.

  5. Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Liu, Dongzhou J; Collaku, Agron

    2018-01-01

    Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

  6. 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.

  7. Computer assisted procedure maintenance

    International Nuclear Information System (INIS)

    Bisio, R.; Hulsund, J. E.; Nilsen, S.

    2004-04-01

    The maintenance of operating procedures in a NPP is a tedious and complicated task. Through the whole life cycle of the procedures they will be dynamic, 'living' documents. Several aspects of the procedure must be considered in a revision process. Pertinent details and attributes of the procedure must be checked. An organizational structure must be created and responsibilities allotted for drafting, revising, reviewing and publishing procedures. Available powerful computer technology provides solutions within document management and computerisation of procedures. These solutions can also support the maintenance of procedures. Not all parts of the procedure life cycle are equally amenable to computerized support. This report looks at the procedure life cycle in todays NPPs and discusses the possibilities associated with introduction of computer technology to assist the maintenance of procedures. (Author)

  8. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date; reopening of administrative record. Food and Drug Administration, HHS. Final rule; delay of effective date; reopening of administrative record.

    Science.gov (United States)

    2000-05-03

    The Food and Drug Administration (FDA) is delaying until October 1, 2001, the effective date and reopening the administrative record to receive additional comments regarding certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). The other provisions of the final rule become effective on December 4, 2000. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the Modernization Act). FDA is delaying the effective date for certain requirements relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record. FDA is also delaying the effective date of another requirement that would prohibit blood centers functioning as "health care entities" to act as wholesale distributors of blood derivatives. The agency is taking this action to address numerous concerns about the provisions raised by affected parties.

  9. 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...

  10. 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…

  11. Safety analysis procedures for PHWR

    International Nuclear Information System (INIS)

    Min, Byung Joo; Kim, Hyoung Tae; Yoo, Kun Joong

    2004-03-01

    The methodology of safety analyses for CANDU reactors in Canada, a vendor country, uses a combination of best-estimate physical models and conservative input parameters so as to minimize the uncertainty of the plant behavior predictions. As using the conservative input parameters, the results of the safety analyses are assured the regulatory requirements such as the public dose, the integrity of fuel and fuel channel, the integrity of containment and reactor structures, etc. However, there is not the comprehensive and systematic procedures for safety analyses for CANDU reactors in Korea. In this regard, the development of the safety analyses procedures for CANDU reactors is being conducted not only to establish the safety analyses system, but also to enhance the quality assurance of the safety assessment. In the first phase of this study, the general procedures of the deterministic safety analyses are developed. The general safety procedures are covered the specification of the initial event, selection of the methodology and accident sequences, computer codes, safety analysis procedures, verification of errors and uncertainties, etc. Finally, These general procedures of the safety analyses are applied to the Large Break Loss Of Coolant Accident (LBLOCA) in Final Safety Analysis Report (FSAR) for Wolsong units 2, 3, 4

  12. Computerized procedures system

    Science.gov (United States)

    Lipner, Melvin H.; Mundy, Roger A.; Franusich, Michael D.

    2010-10-12

    An online data driven computerized procedures system that guides an operator through a complex process facility's operating procedures. The system monitors plant data, processes the data and then, based upon this processing, presents the status of the current procedure step and/or substep to the operator. The system supports multiple users and a single procedure definition supports several interface formats that can be tailored to the individual user. Layered security controls access privileges and revisions are version controlled. The procedures run on a server that is platform independent of the user workstations that the server interfaces with and the user interface supports diverse procedural views.

  13. Payment Procedures for Electronic Government Services

    OpenAIRE

    Pousttchi, Key; Wiedemann, Dietmar Georg

    2005-01-01

    In this paper, we analyse payment procedures for their suitability for electronic government. We provide an overview of the payment procedures currently available on the market, compare the situation in electronic government with the situation in electronic commerce and analyze what we can transfer. Based on functional requirements we propose a scheme that allows public agencies to examine the appropriateness of any given payment procedure for electronic government.

  14. Robotic vascular resections during Whipple procedure.

    Science.gov (United States)

    Allan, Bassan J; Novak, Stephanie M; Hogg, Melissa E; Zeh, Herbert J

    2018-01-01

    Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vascular resections. This report outlines our technique.

  15. Robotic vascular resections during Whipple procedure

    OpenAIRE

    Allan, Bassan J.; Novak, Stephanie M.; Hogg, Melissa E.; Zeh, Herbert J.

    2018-01-01

    Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vas...

  16. Procedures in diagnostic radiology

    International Nuclear Information System (INIS)

    Doyle, T.; Hare, W.S.C.; Thomson, K.; Tess, B.

    1989-01-01

    This book outlines the various procedures necessary for the successful practice of diagnostic radiology. Topics covered are: general principles, imaging of the urinary and gastrointestinal tracts, vascular radiology, arthrography, and miscellaneous diagnostic radiologic procedures

  17. 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....

  18. Procedural Media Representation

    OpenAIRE

    Henrysson, Anders

    2002-01-01

    We present a concept for using procedural techniques to represent media. Procedural methods allow us to represent digital media (2D images, 3D environments etc.) with very little information and to render it photo realistically. Since not all kind of content can be created procedurally, traditional media representations (bitmaps, polygons etc.) must be used as well. We have adopted an object-based media representation where an object can be represented either with a procedure or with its trad...

  19. Classification of radiological procedures

    International Nuclear Information System (INIS)

    1989-01-01

    A classification for departments in Danish hospitals which use radiological procedures. The classification codes consist of 4 digits, where the first 2 are the codes for the main groups. The first digit represents the procedure's topographical object and the second the techniques. The last 2 digits describe individual procedures. (CLS)

  20. Unusual Development of Iatrogenic Complex, Mixed Biliary and Duodenal Fistulas Complicating Roux-en-Y Antrectomy for Stenotic Peptic Disease of the Supraampullary Duodenum Requiring Whipple Procedure: An Uncommon Clinical Dilemma.

    Science.gov (United States)

    Polistina, Francesco A; Costantin, Giorgio; Settin, Alessandro; Lumachi, Franco; Ambrosino, Giovanni

    2010-10-23

    Complex fistulas of the duodenum and biliary tree are severe complications of gastric surgery. The association of duodenal and major biliary fistulas occurs rarely and is a major challenge for treatment. They may occur during virtually any kind of operation, but they are more frequent in cases complicated by the presence of difficult duodenal ulcers or cancer, with a mortality rate of up to 35%. Options for treatment are many and range from simple drainage to extended resections and difficult reconstructions. Conservative treatment is the choice for well-drained fistulas, but some cases require reoperation. Very little is known about reoperation techniques and technical selection of the right patients. We present the case of a complex iatrogenic duodenal and biliary fistula. A 42-year-old Caucasian man with a diagnosis of postoperative peritonitis had been operated on 3 days earlier; an antrectomy with a Roux-en-Y reconstruction for stenotic peptic disease was performed. Conservative treatment was attempted with mixed results. Two more operations were required to achieve a definitive resolution of the fistula and related local complications. The decision was made to perform a pancreatoduodenectomy with subsequent reconstruction on a double jejunal loop. The patient did well and was discharged on postoperative day 17. In our experience pancreaticoduodenectomy may be an effective treatment of refractory and complex iatrogenic fistulas involving both the duodenum and the biliary tree.

  1. Unusual Development of Iatrogenic Complex, Mixed Biliary and Duodenal Fistulas Complicating Roux-en-Y Antrectomy for Stenotic Peptic Disease of the Supraampullary Duodenum Requiring Whipple Procedure: An Uncommon Clinical Dilemma

    Directory of Open Access Journals (Sweden)

    Francesco A. Polistina

    2010-10-01

    Full Text Available Complex fistulas of the duodenum and biliary tree are severe complications of gastric surgery. The association of duodenal and major biliary fistulas occurs rarely and is a major challenge for treatment. They may occur during virtually any kind of operation, but they are more frequent in cases complicated by the presence of difficult duodenal ulcers or cancer, with a mortality rate of up to 35%. Options for treatment are many and range from simple drainage to extended resections and difficult reconstructions. Conservative treatment is the choice for well-drained fistulas, but some cases require reoperation. Very little is known about reoperation techniques and technical selection of the right patients. We present the case of a complex iatrogenic duodenal and biliary fistula. A 42-year-old Caucasian man with a diagnosis of postoperative peritonitis had been operated on 3 days earlier; an antrectomy with a Roux-en-Y reconstruction for stenotic peptic disease was performed. Conservative treatment was attempted with mixed results. Two more operations were required to achieve a definitive resolution of the fistula and related local complications. The decision was made to perform a pancreatoduodenectomy with subsequent reconstruction on a double jejunal loop. The patient did well and was discharged on postoperative day 17. In our experience pancreaticoduodenectomy may be an effective treatment of refractory and complex iatrogenic fistulas involving both the duodenum and the biliary tree.

  2. 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

  3. 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

  4. 25 CFR 225.21 - Negotiation procedures.

    Science.gov (United States)

    2010-04-01

    ... setting forth the duration of the minerals agreement; (3) A statement providing indemnification to the... accounting and mineral valuation procedures; (8) Provisions establishing operating and management procedures... refusal by the Indian mineral owner in the event of a proposed assignment; (10) Bond requirements; (11...

  5. W-087 Acceptance test procedure. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, A.W.

    1997-06-10

    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.

  6. 22 CFR 226.71 - Closeout procedures.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Closeout procedures. 226.71 Section 226.71 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS After-the-Award Requirements § 226.71 Closeout procedures. (a) Recipients shall...

  7. 22 CFR 92.37 - Authentication procedure.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication procedure. 92.37 Section 92.37... Notarial Acts § 92.37 Authentication procedure. (a) The consular officer must compare the foreign official...) Where the State law requires the consular officer's certificate of authentication to show that the...

  8. 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. ...

  9. 21 CFR 314.530 - Withdrawal procedures.

    Science.gov (United States)

    2010-04-01

    ... Serious or Life-Threatening Illnesses § 314.530 Withdrawal procedures. (a) For new drugs approved under... benefit; (2) The applicant fails to perform the required postmarketing study with due diligence; (3) Use...

  10. 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

  11. 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).

  12. 48 CFR 432.006-4 - Procedures.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS CONTRACT FINANCING 432.006-4 Procedures. (a) Immediately upon submittal of the referral described... decision making process. (c) The OIG will determine the need for and the extent of an investigation. (d...

  13. 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

  14. 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.

  15. 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

  16. Waste segregation procedures and benefits

    International Nuclear Information System (INIS)

    Fish, J.D.; Massey, C.D.; Ward, S.J.

    1990-01-01

    Segregation is a critical first step in handling hazardous and radioactive materials to minimize the generation of regulated wastes. In addition, segregation can significantly reduce the complexity and the total cost of managing waste. Procedures at Sandia National Laboratories, Albuquerque require that wastes be segregated, first, by waste type (acids, solvents, low level radioactive, mixed, classified, etc.). Higher level segregation requirements, currently under development, are aimed at enhancing the possibilities for recovery, recycle and reapplication; reducing waste volumes; reducing waste disposal costs, and facilitating packaging storage, shipping and disposal. 2 tabs

  17. BWR emergency procedure guidelines

    International Nuclear Information System (INIS)

    Post, J.S.; Karner, E.F.; Stratman, R.A.

    1984-01-01

    This chapter describes plans for dealing with reactor accidents developed by the Boiling Water Reactor (BWR) Owners' Group in response to post-Three Mile Island US NRC requirements. The devised Emergency Procedure Guidelines (EPGs), applicable to all BWRs, are symptom-based rather than event-based. According to the EPGs, the operator does not need to identify what event is occurring in the plant in order to decide what action to take, but need only observe the symptoms (values and trends of key control parameters) which exist and take appropriate action to control these symptoms. The original objective was to provide reactor operator guidance in responding to a small break loss-of-coolant accident (LOCA), but subsequent revisions have included other types of reactor accidents. Topics considered include the reactor pressure vessel (RPV) control guideline, the primary containment control guideline, the secondary containment control guideline, the radioactivity release control guideline, multiple failures vs. the design basis, safe limits vs. technical specifications, the technical status, licensing, and implementation. The EPGs are based upon maintaining both adequate core cooling and primary containment integrity

  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. Analytical procedures. Pt. 4

    International Nuclear Information System (INIS)

    Rackwitz, R.

    1985-01-01

    The semi-analytical procedures are summarized under the heading 'first or second-order reliability method'. The asymptotic aggravation of the theory was repeatedly hinted at. In supporting structures the probability of outage of components always is also a function of the condition of all other components. It depends moreover on the stress affecting mostly all components. This fact causes a marked reduction of the effect of redundant component arrangements in the system. It moreover requires very special formulations. Although theoretically interesting and practically important developments will leave their mark on the further progress of the theory, the statements obtained by those approaches will continue to depend on how closely the chosen physical relationships and stoachstic models can come to the scatter quantities. Sensitivity studies show that these are partly aspects of substantially higher importance with a view to decision criteria than the refinement of the (probabilistic) method. Questions of relevance and reliability of data and their adequate treatment in reliability analyses seem to rank higher in order of sequence than exaggerated demands on methodics. (orig./HP) [de

  20. 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

  1. 48 CFR 32.003 - Simplified acquisition procedures financing.

    Science.gov (United States)

    2010-10-01

    ... procedures financing. 32.003 Section 32.003 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 32.003 Simplified acquisition procedures financing. Unless agency regulations otherwise permit, contract financing shall not be provided for...

  2. 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)

  3. Civil Procedure In Denmark

    DEFF Research Database (Denmark)

    Werlauff, Erik

    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......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...

  4. Procedures monitoring and MAAP analysis

    International Nuclear Information System (INIS)

    May, R.S.

    1991-01-01

    Numerous studies of severe accidents in light water reactors have shown that operator response can play a crucial role in the predicted outcomes of dominant accident scenarios. MAAP provides the capability to specify certain operator actions as input data. However, making reasonable assumptions about the nature and timing of operator response requires substantial knowledge about plant practices and procedures and what they imply for the event being analyzed. The appearance of knowledge based software technology in the mid-1980s provided a natural format for representing and maintaining procedures as IF-THEN rules. The boiling water reactor (BWR) Emergency Operating Procedures Tracking System (EOPTS) was composed of a rule base of procedures and a dedicated inference engine (problem-solver). Based on the general approach and experience of EOPTS, the authors have developed a prototype procedures monitoring system that reads MAAP transient output files and evaluate the EOP messages and instructions that would be implied during each transient time interval. The prototype system was built using the NEXPERT OBJECT expert system development system, running on a 386-class personal computer with 4 MB of memory. The limited scope prototype includes a reduced set of BWR6 EOPs procedures evaluation on a coarse time interval, a simple text-based user interface, and a summary-report generator. The prototype, which is limited to batch-mode analysis of MAAP output, is intended to demonstrate the concept and aid in the design of a production system, which will involve a direct link to MAAP and interactive capabilities

  5. Spline-procedures

    International Nuclear Information System (INIS)

    Schmidt, R.

    1976-12-01

    This report contains a short introduction to spline functions as well as a complete description of the spline procedures presently available in the HMI-library. These include polynomial splines (using either B-splines or one-sided basis representations) and natural splines, as well as their application to interpolation, quasiinterpolation, L 2 -, and Tchebycheff approximation. Special procedures are included for the case of cubic splines. Complete test examples with input and output are provided for each of the procedures. (orig.) [de

  6. 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.

  7. 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...

  8. Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

    Science.gov (United States)

    Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

    2013-10-01

    To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

  9. Handbook of radiologic procedures

    International Nuclear Information System (INIS)

    Hedgcock, M.

    1986-01-01

    This book is organized around radiologic procedures with each discussed from the points of view of: indications, contraindications, materials, method of procedures and complications. Covered in this book are: emergency radiology chest radiology, bone radiology, gastrointestinal radiology, GU radiology, pediatric radiology, computerized tomography, neuroradiology, visceral and peripheral angiography, cardiovascular radiology, nuclear medicine, lymphangiography, and mammography

  10. Decision-making Procedures

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  11. Maintenance procedure upgrade programs

    International Nuclear Information System (INIS)

    Campbell, J.J.; Zimmerman, C.M.

    1988-01-01

    This paper describes a systematic approach to upgrading nuclear power plant maintenance procedures. The approach consists of four phases: diagnosis, program planning, program implementation, and program evaluation. Each phase is explained as a series of steps to ensure that all factors in a procedure upgrade program are considered

  12. Actor-Network Procedures

    NARCIS (Netherlands)

    Pavlovic, Dusko; Meadows, Catherine; Ramanujam, R.; Ramaswamy, Srini

    2012-01-01

    In this paper we propose actor-networks as a formal model of computation in heterogenous networks of computers, humans and their devices, where these new procedures run; and we introduce Procedure Derivation Logic (PDL) as a framework for reasoning about security in actor-networks, as an extension

  13. Analytical procedures. Pt. 1

    International Nuclear Information System (INIS)

    Weber, G.

    1985-01-01

    In analytical procedures (Boole procedures) there is certain to be a close relationship between the safety assessment and reliability assessment of technical facilities. The paper gives an overview of the organization of models, fault trees, the probabilistic evaluation of systems, evaluation with minimum steps or minimum paths regarding statistically dependent components and of systems liable to suffer different kinds of outages. (orig.) [de

  14. 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

  15. 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...

  16. 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

  17. 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

  18. Packaging requirements and procedures for the transport of radioactive materials

    International Nuclear Information System (INIS)

    White, M.C.

    1980-01-01

    Canadian regulations on the transportation of radioactive materials are based on those formulated by the IAEA. A synopsis of these regulations is presented, and the background to certain key provisions is explained. (LL)

  19. Inspection system performance test procedure

    International Nuclear Information System (INIS)

    Jensen, C.E.

    1995-01-01

    This procedure establishes requirements to administer a performance demonstration test. The test is to demonstrate that the double-shell tank inspection system (DSTIS) supplied by the contractor performs in accordance with the WHC-S-4108, Double-Shell Tank Ultrasonic Inspection Performance Specification, Rev. 2-A, January, 1995. The inspection system is intended to provide ultrasonic (UT) and visual data to determine integrity of the Westinghouse Hanford Company (WHC) site underground waste tanks. The robotic inspection system consists of the following major sub-systems (modules) and components: Mobile control center; Deployment module; Cable management assembly; Robot mechanism; Ultrasonic testing system; Visual testing system; Pneumatic system; Electrical system; and Control system

  20. 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

  1. HASL procedures manual

    International Nuclear Information System (INIS)

    1980-08-01

    Addition and corrections to the following sections of the HASL Procedures Manual are provided: Table of Contents; Bibliography; Fallout Collection Methods; Wet/Dry Fallout Collection; Fluoride in Soil and Sediment; Strontium-90; Natural Series; Alpha Emitters; and Gamma Emitters

  2. 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

  3. 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 ...

  4. Modified arthroscopic Brostrom procedure.

    Science.gov (United States)

    Lui, Tun Hing

    2015-09-01

    The open modified Brostrom anatomic repair technique is widely accepted as the reference standard for lateral ankle stabilization. However, there is high incidence of intra-articular pathologies associated with chronic lateral ankle instability which may not be addressed by an isolated open Brostrom procedure. Arthroscopic Brostrom procedure with suture anchor has been described for anatomic repair of chronic lateral ankle instability and management of intra-articular lesions. However, the complication rates seemed to be higher than open Brostrom procedure. Modification of the arthroscopic Brostrom procedure with the use of bone tunnel may reduce the risk of certain complications. Copyright © 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  5. 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...

  6. Cosmetic Procedure Questions

    Science.gov (United States)

    ... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... time of their procedure. 6. What are my pain management and anesthesia options? To help avoid the ...

  7. Special Blood Donation Procedures

    Science.gov (United States)

    ... Blood Products Special Blood Donation Procedures Precautions and Adverse Reactions During Blood Transfusion (See Overview of Blood Transfusion .) Plateletpheresis (platelet donation) In plateletpheresis, a donor gives only platelets rather than whole blood. Whole ...

  8. 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)

  9. Radiochemical procedures and techniques

    International Nuclear Information System (INIS)

    Flynn, K.

    1975-04-01

    A summary is presented of the radiochemical procedures and techniques currently in use by the Chemistry Division Nuclear Chemistry Group at Argonne National Laboratory for the analysis of radioactive samples. (U.S.)

  10. 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.

  11. Bariatric Surgery Procedures

    Science.gov (United States)

    ... Meetings of Interest Online Education Job Board CME Policies CBN Fellowship Certificate Research Grant Program Resources All Resources Approved Procedures Patient Safety Vignettes Dr. Mason Historical Library Governing Documents Guidelines Access and Insurance Position and ...

  12. Can proceduralization support coping with the unexpected?

    Energy Technology Data Exchange (ETDEWEB)

    Norros, Leena; Savioja, Paula; Liinasuo, Marja; Wahlstrom, Mikael [VTT Technical Research Centre of Finland, Vuorimiehentie (Finland)

    2014-08-15

    Operations of safety critical industries unquestionably require a diversity of technical and organizational control measures to increase stability and predictability of the complex sociotechnical systems. Nevertheless, experiences from recent severe accidents and results of safety research have questioned the effectiveness of the prevailing safety management strategy that mainly relies on standardization and designed-in defenses. This paper discusses the identified need to balance between stability and flexibility in a concrete safety issue, i.e., proceduralization. The main research problem of our study is whether procedure guided practice can offer sufficient support for flexibility of operating activity. We shall frame our study with the help of a model that explains different aspects of procedures. We then elaborate how these different aspects were considered empirically in our 3-phase study. In the first study we interviewed 62 main control room operators and asked how they consider procedures to support balancing. In the second study we observed in detail 12 NPP operator crews' activity in a simulated loss-of-coolant accident. In a third study we inquired 5 procedure designers about their conceptions concerning procedure guidance in operator work. Drawing on either interview or behavioral data we analyzed the personnel's stance to the flexibility and stability balancing, and how the conceptions portray in the practices of procedure usage. Our results demonstrate that the operators are aware of the need for balancing flexibility and stability and consider successful balancing to represent 'good' professional action. In actual action many operators, however, tend towards more straightforward following of procedures. Designers also see the capability for balancing stability and flexibility as a key operator competence but describe actual acting simply as procedure-following. According to the documents of the nuclear community, procedure

  13. Can proceduralization support coping with the unexpected?

    International Nuclear Information System (INIS)

    Norros, Leena; Savioja, Paula; Liinasuo, Marja; Wahlstrom, Mikael

    2014-01-01

    Operations of safety critical industries unquestionably require a diversity of technical and organizational control measures to increase stability and predictability of the complex sociotechnical systems. Nevertheless, experiences from recent severe accidents and results of safety research have questioned the effectiveness of the prevailing safety management strategy that mainly relies on standardization and designed-in defenses. This paper discusses the identified need to balance between stability and flexibility in a concrete safety issue, i.e., proceduralization. The main research problem of our study is whether procedure guided practice can offer sufficient support for flexibility of operating activity. We shall frame our study with the help of a model that explains different aspects of procedures. We then elaborate how these different aspects were considered empirically in our 3-phase study. In the first study we interviewed 62 main control room operators and asked how they consider procedures to support balancing. In the second study we observed in detail 12 NPP operator crews' activity in a simulated loss-of-coolant accident. In a third study we inquired 5 procedure designers about their conceptions concerning procedure guidance in operator work. Drawing on either interview or behavioral data we analyzed the personnel's stance to the flexibility and stability balancing, and how the conceptions portray in the practices of procedure usage. Our results demonstrate that the operators are aware of the need for balancing flexibility and stability and consider successful balancing to represent 'good' professional action. In actual action many operators, however, tend towards more straightforward following of procedures. Designers also see the capability for balancing stability and flexibility as a key operator competence but describe actual acting simply as procedure-following. According to the documents of the nuclear community, procedure

  14. 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

  15. Efficient Reanalysis Procedures in Structural Topology Optimization

    DEFF Research Database (Denmark)

    Amir, Oded

    This thesis examines efficient solution procedures for the structural analysis problem within topology optimization. The research is motivated by the observation that when the nested approach to structural optimization is applied, most of the computational effort is invested in repeated solutions...... on approximate reanalysis. For cases where memory limitations require the utilization of iterative equation solvers, we suggest efficient procedures based on alternative termination criteria for such solvers. These approaches are tested on two- and three-dimensional topology optimization problems including...

  16. PENILE ENHANCEMENT PROCEDURES: UROLOGICAL AND ETHICOLEGAL ISSUES

    OpenAIRE

    Marco Vella

    2012-01-01

    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...

  17. 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...

  18. 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...

  19. 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...

  20. 22 CFR 201.23 - Procurement under private sector procedures.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Procurement under private sector procedures... § 201.23 Procurement under private sector procedures. (a) General requirements. Procurements under private sector procedures will normally be carried out by importers using negotiated procurement...

  1. 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

  2. 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

  3. 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.

  4. 47 CFR 1.2112 - Ownership disclosure requirements for applications.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Ownership disclosure requirements for... PROCEDURE Competitive Bidding Proceedings General Procedures § 1.2112 Ownership disclosure requirements for... agreements, management agreements, franchise agreements, spectrum leasing arrangements, spectrum resale...

  5. 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

  6. 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.

  7. 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

  8. Evaluation of safeguards procedures: a summary of a methodology

    International Nuclear Information System (INIS)

    Salisbury, J.D.; Savage, J.W.

    1979-01-01

    A methodology for the evaluation of safeguards procedures is described. As presently conceptualized, the methodology will consist of the following steps: (1) expansion of the general protection requirements that are contained in the NRC regulations into more detailed but still generic requirements for use at the working level; (2) development of techniques and formats for using the working-level requirements in an evaluation; (3) development of a technique for converting specific facility protection procedures into a format that will allow comparison with the working-level requirements; (4) development of an evaluation technique for comparing the facility protection procedures to determine if they meet the protection requirements

  9. 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.

  10. COPMA-III - Intelligent handling of existing procedures

    International Nuclear Information System (INIS)

    Hulsund, John-Einar; Jung, Yeonsub; Nilsen, Svein

    1999-04-01

    This report describes how COPMA-III makes it possible to enhance old procedures without having to change much of their original layout. By means of COPMA-III one can insert into the old procedure text tags that describe the 'meaning' of the various textual elements in the procedure. Those tags can be made invisible to the person using the procedure, but the computer is able to inspect the tags and give appropriate assistance in carrying through the procedure. Previous versions of COPMA required a reformulation and most often a re-structuring of the procedures before taking them into use. A fixed set of instructions and a fixed procedure structure made the computerised procedure different from the original procedure (in most cases). This is no more so in COPMA-III. By means of small procedural elements (microelements), it is possible to configure the COPMA-III system to fit the set of instructions and the procedure structure that is being used in the old procedure system. This report describes an example case, starting with an old procedure, goes through a set of working steps and ends up with a procedure having exactly the same appearance as the old procedure, but having assistance from the COPMA-III system in executing the procedure (author) (ml)

  11. Procedural learning and dyslexia.

    Science.gov (United States)

    Nicolson, R I; Fawcett, A J; Brookes, R L; Needle, J

    2010-08-01

    Three major 'neural systems', specialized for different types of information processing, are the sensory, declarative, and procedural systems. It has been proposed (Trends Neurosci., 30(4), 135-141) that dyslexia may be attributable to impaired function in the procedural system together with intact declarative function. We provide a brief overview of the increasing evidence relating to the hypothesis, noting that the framework involves two main claims: first that 'neural systems' provides a productive level of description avoiding the underspecificity of cognitive descriptions and the overspecificity of brain structural accounts; and second that a distinctive feature of procedural learning is its extended time course, covering from minutes to months. In this article, we focus on the second claim. Three studies-speeded single word reading, long-term response learning, and overnight skill consolidation-are reviewed which together provide clear evidence of difficulties in procedural learning for individuals with dyslexia, even when the tasks are outside the literacy domain. The educational implications of the results are then discussed, and in particular the potential difficulties that impaired overnight procedural consolidation would entail. It is proposed that response to intervention could be better predicted if diagnostic tests on the different forms of learning were first undertaken. 2010 John Wiley & Sons, Ltd.

  12. 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

  13. 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

  14. 38 CFR 39.10 - Application requirements.

    Science.gov (United States)

    2010-07-01

    ...-10) Grant Requirements and Procedures § 39.10 Application requirements. (a) For a project to be..., etc., (10) Economic activities, (11) Cultural resources, (12) Aesthetics, (13) Residential population...

  15. 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.

  16. Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

    Directory of Open Access Journals (Sweden)

    Jing-Bo Peng

    2014-01-01

    Full Text Available A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA in human plasma. Acitretin was used as the internal standard (IS. After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE, ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE–methanol–acetic acid, 50:50:0.5, v/v and 60% phase B (water–methanol–acetic acid, 50:50:0.5, v/v with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45–217.00 ng/mL (r ≥ 0.999 with a lower limit of quantitation (LLOQ of 0.45 ng/mL. The intra- and inter-day precisions values were below 8% relative standard deviation and the accuracy was from 98.98% to 106.19% in terms of relative error. The validated method was successfully applied in a bioequivalence study of ATRA in Chinese healthy volunteers.

  17. Procedure guideline for thyroid scintigraphy (version 3)

    International Nuclear Information System (INIS)

    Dietlein, M.; Schicha, H.; Eschner, W.; Deutsche Gesellschaft fuer Medizinische Physik; Koeln Univ.; Leisner, B.; Allgemeines Krankenhaus St. Georg, Hamburg; Reiners, C.; Wuerzburg Univ.

    2007-01-01

    The version 3 of the procedure guideline for thyroid scintigraphy is an update of the procedure guideline previously published in 2003. The interpretation of the scintigraphy requires the knowledge of the patients' history, the palpation of the neck, the laboratory parameters and of the sonography. The interpretation of the technetium-99m uptake requires the knowledge of the TSH-level. As a consequence of the improved alimentary iodine supply the 99m Tc-uptake has decreased; 100 000 counts per scintigraphy should be acquired. For this, an imaging time of 10 minutes is generally needed using a high resolution collimator for thyroid imaging. (orig.)

  18. 78 FR 16779 - Type Certification Procedures for Changed Products

    Science.gov (United States)

    2013-03-19

    ...-8994; Amdt. No. 21-96] RIN 2120-AK19 Type Certification Procedures for Changed Products AGENCY: Federal... requirements for the certification of changes to type-certificated products. The revision required the... entitled, ``Type Certification Procedures for Changed Products'' (December 4, 2012, 77 FR 71691). The 2000...

  19. Motive Criminal Procedure Evidence

    Directory of Open Access Journals (Sweden)

    В. В. Вапнярчук

    2015-03-01

    Full Text Available In the article the need for such a level of mental regulation of behavior of proving motivation. The latter refers to internal motivation conscious entity Criminal Procedure proof, due to specific needs, interests and goals that cause a person to act rishymist. Detailed attention is given to the first two determinants, namely the nature of needs and interests. In particular, analyzes highlighted in the literature variety of needs (physiological, ekzistentsionalni, social, prestige, cognitive, aesthetic and spiritual and the manifestation of some of them in the criminal procedural proof.

  20. 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.

  1. 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

  2. 49 CFR 1503.101 - TSA requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false TSA requirements. 1503.101 Section 1503.101... Scope of Investigative and Enforcement Procedures § 1503.101 TSA requirements. (a) The investigative and enforcement procedures in this part apply to TSA's investigation and enforcement of violations of TSA...

  3. 49 CFR 601.45 - Required information.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Required information. 601.45 Section 601.45 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ORGANIZATION, FUNCTIONS, AND PROCEDURES Emergency Procedures for Public Transportation Systems § 601.45 Required...

  4. 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...

  5. Electronic procedure distribution

    International Nuclear Information System (INIS)

    Slone, B.J. III; Richardson, C.E.

    1993-01-01

    Printed procedures can offer a mix of text and graphic information that improves readability and increases understanding. A typical procedure uses illustrations and graphics to clarify concepts, a variety of type styles and weights to make it easier to find different topics and sections, white space to improve readability, and familiar navigational clues such as page numbers and topic headers. Initially, electronic procedure systems had limited typeface options, often only a single typeface, with no capability for enhancing readability by varying type size bolding, italicizing, or underlining, and no ability to include graphics. Even recently, many text-only electronic procedures were originally created in a modern What-You-See-Is-What-You-Get (WYSI-WYG) document authoring system, only to be converted to pages and pages of plain type for electronic distribution. Given the choice of paper or on-line producers, most users have chosen paper for its readability. But current-generation electronic document systems that use formatted text and embedded graphics offer users vastly improved readability. Further, they are offering ever-better search tools to enable rapid location of material of interest

  6. The nuclear licensing procedure

    International Nuclear Information System (INIS)

    Wagner, H.

    1976-01-01

    To begin with, the present nuclear licensing procedure is illustrated by a diagram. The relationship between the state and the Laender, the various experts (GRS - IRS + LRA -, TUEV, DWD, university institutes, firms of consulting engineers, etc), participation of the public, e.g. publication of the relevant documents, questions, objections (made by individuals or by groups such as citizens' initiatives), public discussion, official notice, appeals against the decision, the right of immediate execution of the decision are shortly dealt with. Finally, ways to improve the licensing procedure are discussed, from the evaluation of the documents to be submitted, published, and examined by the authorities (and their experts) up to an improvement of the administrative procedure. An improved licensing procedure should satisfy the well-founded claims of the public for more transparency as well as the equally justifiable claims of industry and utilities in order to ensure that the citizens' legal right to have safe and adequate electric power is guaranteed. The updated energy programme established by the Federal Government is mentioned along with the effectiveness of dealing with nuclear problems on the various levels of a Land government. (orig.) [de

  7. 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

  8. Pneumomediastinum after odontologic procedure

    International Nuclear Information System (INIS)

    Olivella C, Fabio Alejandro; Bermudez G, Mary; Hidalgo M, Patricia; Sanchez M, Jully Mariana; Solarte R, Ivan; Uriza C, Felipe

    2005-01-01

    The sudden increase in alveolar pressure is a frequent cause of pneumomediastinum, but there are other reasons that could lead to it such as airway or esophagus trauma. The pneumomediastinum, which has been produced after dental procedures, is very rare and product deserves special attention by dentists and medical personnel in order to get its soon recognition and handling

  9. 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,…

  10. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    properties of the analysed data. The broad theoretical background of robust procedures was given as a very useful supplement to the classical methods, and a new tool, based on robust PCA, aiming at identifying Rayleigh and Raman scatters in excitation-mission (EEM) data was developed. The results show...

  11. 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

  12. 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.

  13. 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

  14. Experiments with Cloze Procedure

    Science.gov (United States)

    Evans, Gordon; Haastrup, Kirsten

    1976-01-01

    The Nordic Test Development Group prepared proficiency tests of English designed to provide reliable information on which to base decisions as to whether a candidate would be able to function in a job as described or whether he could be trained to do so. Two subtests used a modified cloze procedure. (Author/CFM)

  15. 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

  16. 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

  17. 22 CFR 226.44 - Procurement procedures.

    Science.gov (United States)

    2010-04-01

    ... Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.44 Procurement procedures. (a... and assistance, as appropriate, of such organizations as the Small Business Administration and the...

  18. 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...

  19. 5 CFR 5502.105 - Agency procedures.

    Science.gov (United States)

    2010-01-01

    ....105 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL FINANCIAL DISCLOSURE REQUIREMENTS FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5502.105 Agency procedures. (a) The designated agency ethics official or, with the concurrence of the designated agency ethics official, each of...

  20. Military Publications, Index of Test Operations Procedures

    Science.gov (United States)

    1981-10-01

    serial number, aad design information for majur components. Prescribes vehicle, major component, and system descrip- tive elements required; such as...mount operating characteristics. Discusses preparation for test, instrumentation, and facil- ities. Describes procedures for force measurement, carriage...backlash and accuracy, turret friction, gun balance, manual handcrank force , manual response ratio, weapon and sighting system backlash, power controller

  1. 78 FR 21517 - Practices and Procedures

    Science.gov (United States)

    2013-04-11

    ... electronic format, including word processing applications, HTML or PDF. Commenters are asked to use a text format and not an image format for attachments. The email should contain a subject line indicating that... Administrative Procedure Act (APA). However, an exemption from notice and comment rulemaking requirements exists...

  2. 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)

  3. 48 CFR 32.006-4 - Procedures.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS CONTRACT FINANCING 32.006-4 Procedures. (a) In any case in which an agency's remedy coordination...) of this subsection. (e) Before making a decision to reduce or suspend further payments, the agency... determination and decision. (g) The agency shall retain in its files the written justification for each— (1...

  4. 48 CFR 17.403 - Procedures.

    Science.gov (United States)

    2010-10-01

    ... CONTRACT TYPES SPECIAL CONTRACTING METHODS Leader Company Contracting 17.403 Procedures. (a) The contracting officer may award a prime contract to a— (1) Leader company, obligating it to subcontract a designated portion of the required end items to a specified follower company and to assist it to produce the...

  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. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

    Science.gov (United States)

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-06-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

  7. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

    Directory of Open Access Journals (Sweden)

    André Daher

    2015-06-01

    Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

  8. Cancer pancreatis, diagnostic procedures

    International Nuclear Information System (INIS)

    Graadal, Oe.; Schlichting, E.; Aasen, A.O.; Stadaas, J.O.

    1990-01-01

    151 patients treated for carcinoma of the pancreas at Ullevaal Hospital (Oslo University) during the period 1980-89 were studied. The most common initial symptom was abdominal pain. Other frequent debut symptoms were loss of weight and jaundice. ERCP and PTC were found to be the best diagnostic procedures. CT or ultrasonography were normal in 10-20% of the patients. Nearly all tumors of the pancreas were found by the ERCP procedure. Also angiography was used to evaluate operability of the pancreas tumor, but was found to be a very uncertain diagnostic method. This method will not be used in the future evaluation of patients with cancer of the pancreas. 13 refs., 1 fig., 2 tabs

  9. 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.

  10. Internal Control Organization Procedure

    OpenAIRE

    Radu Dorin Lenghel

    2013-01-01

    Internal control represents the totality of policies and procedures adopted by management, which contribute: to the fulfilment of managerial objectives, to the prevention and detection of frauds or errors, to the accuracy and exhaustiveness of accounting entries, as well as to the preparation in due course of financial accounting information. Internal control represents a managerial instrument which assures the fulfilment of objectives of the entity, being an ongoing process in which administ...

  11. Analytical Procedures for Testability.

    Science.gov (United States)

    1983-01-01

    Beat Internal Classifications", AD: A018516. "A System of Computer Aided Diagnosis with Blood Serum Chemistry Tests and Bayesian Statistics", AD: 786284...6 LIST OF TALS .. 1. Truth Table ......................................... 49 2. Covering Problem .............................. 93 3. Primary and...quential classification procedure in a coronary care ward is evaluated. In the toxicology field "A System of Computer Aided Diagnosis with Blood Serum

  12. The TOMAX-procedure

    OpenAIRE

    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 the non-functional “penile” nerve on one side to bypass the LSL. Our goal was to increase LSL patients’ sexual health by restoring penile sensation: we show that TOMAX can achieve dramatic improvem...

  13. Start-up procedure

    International Nuclear Information System (INIS)

    Marchl, A.; Krebs, W.D.; Aleite, W.

    1975-01-01

    The start-up procedure will be shown on a pressurized water reactor, although most of the activities will occur similarly in other reactor types. The commissioning time can be divided into 5 sections, the phases A to E together lasting 26 months. Subsequently there are a test run of one month and the handling-over of the plant to the operator. A survey of the commissioning sections with several important main events is shown. (orig./TK) [de

  14. [Procedural learning disorder: neuropsychological characteristics].

    Science.gov (United States)

    Crespo-Eguílaz, N; Narbona, J

    This research aims at neurocognitive delineation of the core features of procedural learning disorder (PLD), otherwise labeled as motor coordination disorder or non-verbal learning disorder. A sample of 209 correlative outpatients (73% males), aged 6-12 years, all of them having QI ranging from 81 to 120, was clustered into the following neurobehavioural groups: PLD (n = 16), PLD plus attention deficit hyperactivity disorder (ADHD) (n = 37), ADHD combined type (n = 47), ADHD predominantly inattentive type (n = 23), specific language impairment (n = 68), and semantic-pragmatic language impairment (n = 18). Two additional groups of patients were included for some comparisons: children with periventricular leukomalacia (PVL) without learning disability (n = 8) or associating PLD (n = 17). A set of behavioural scales and neurocognitive tests was used to evaluate verbal and non-verbal IQ, attention, impulsivity control, visuo-motor coordination, declarative memory, procedural memory and learning, formal and functional dimensions of language, peer relationships and academic achievement. Parametric analysis were used to test the differences and similarities of neurobehavioural variables between groups. Our results allow us to conclude that PLD implies a difficult acquisition of automatized motor, cognitive and communicative abilities required in school work and peer social relationships. PLD is different from autistic spectrum disorders. It is frequently associated to inattentive ADHD. Operational criteria for diagnosis of PLD are proposed, according to our results. A bilateral posterior parietal dysfunction is a plausible explanation of its physiopathology. Preserved general intelligence and formal linguistic abilities are the clues for intervention designs.

  15. Systems Engineering Management Procedures

    Science.gov (United States)

    1966-03-10

    hls -iii-rit. -miiiirme 4 --tandnirdized hle iil*ri oa;iu ’ -enperfrm)a- -yýfefi ~lall uitm l--im eniai~ atar n which will lumPremiiieuiea -. v-imli m...with standard component/part selection. and de- tile total system requirements stated in the Sys- tailed functional and physical interfaces: eval- tern...system survivability requirAent. As physical , interface, time, environment, use of these facility requirements are bei developed, standard perts; and

  16. Coal pillar design procedures

    CSIR Research Space (South Africa)

    York, G

    2000-03-01

    Full Text Available Final Project Report Coal pillar design procedures G. York, I. Canbulat, B.W. Jack Research agency: CSIR Mining Technology Project number: COL 337 Date: March 2000 2 Executive Summary Examination of collapsed pillar cases outside of the empirical... in strength occurs with increasing specimen size. 45 40 35 30 25 20 15 10 5 0 20 40 60 80 100 120 140 160 UNIAX IA L COMPR EHEN SIV E S TR ENG TH (M Pa ) CUBE SIZE (cm) Figure 1...

  17. Emergency procedures in London

    International Nuclear Information System (INIS)

    Cree, D.

    1984-01-01

    This chapter discusses the following: emergency services (fire brigade, ambulance and police) that would be involved in dealing with an accident to a nuclear fuel flask in transport through London, with special reference to procedures used by the Metropolitan Police; geographical area covered by Metropolitan Police; initiation of action; decision whether to evacuate the area of the accident; examples of action taken to deal with non-radiation accidents (in absence of any example of relevant radiation accident); specific instructions, or advice, to police relating to the movement of irradiated fuel; training exercises. (U.K.)

  18. 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.

  19. Remote handling procedures in JET

    International Nuclear Information System (INIS)

    Raimondi, T.; Huguet, M.

    1976-01-01

    Remote maintenance will be needed in the second phase of operation due to the structural activation produced by deuterium-tritium discharges. Priority will be given to tasks which require frequent intervention, but efforts will be made also to tackle larger operations such as replacement of an octant. Owing to the variety and unpredictability of the operations which may be required, general purpose telemanipulator and TV systems will be used, mounted on versatile articulated supports capable of reaching the various parts of the machine. An experimental programme is planned to test the envisaged equipment and develop procedures for carrying out the various tasks as they are more clearly identified. Design of peripheral equipment for easy accessibility, choice of simple connection methods, development of auxiliary tools, as well as careful programming of the operations, will be essential for successful remote maintenance. The effort put into these areas will, however, also result in considerable time saving during the assembly and maintenance in non-active conditions. Preliminary feasibility tests of some difficult operations have already been done with a force-reflecting servo-manipulator and two TV sets for front and side viewing. Leak identification and precision welding for vacuum tightness were demonstrated

  20. 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

  1. 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

  2. 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

  3. Radiation dose electrophysiology procedures

    International Nuclear Information System (INIS)

    Hernandez-Armas, J.; Rodriguez, A.; Catalan, A.; Hernandez Armas, O.; Luque Japon, L.; Moral, S.; Barroso, L.; Rfuez-Hdez, R.

    2006-01-01

    The aim of this paper has been to measure and analyse some of the parameters which are directly related with the doses given to patients in two electrophysiology procedures: diagnosis and ablation with radiofrequency. 16 patients were considered in this study. 13 them had an ablation with radiofrequency at the Unit of Electrophysiology at the University Hospital of the Canaries, La Laguna., Tenerife. The results of skin doses, in the ablation cases, were higher than 2 Gy (threshold of some deterministic effects). The average value was 1.1 Gy. The personal doses, measured under the lead apron, for physician and nurses were 4 and 3 micro Sievert. These results emphasised the necessity of radiation protection measures in order to reduce, ad much as possible, the doses to patients. (Author)

  4. Decommissioning licensing procedure

    International Nuclear Information System (INIS)

    Perello, M.

    1979-01-01

    Decommissioning or closure of a nuclear power plant, defined as the fact that takes place from the moment that the plant stops producing for the purpose it was built, is causing preocupation. So this specialist meeting on Regulatory Review seems to be the right place for presenting and discusing the need of considering the decommissioning in the safety analysis report. The main goal of this paper related to the licensing procedure is to suggest the need of a new chapter in the Preliminary Safety Analysis Report (P.S.A.R.) dealing with the decommissioning of the nuclear power plant. Therefore, after a brief introduction the problem is exposed from the point of view of nuclear safety and finally a format of the new chapter is proposed. (author)

  5. 7 CFR 1735.94 - Final approval and closing procedure.

    Science.gov (United States)

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Requirements for All Acquisitions and Mergers § 1735.94 Final approval and closing procedure. (a) Legal documents relating to the acquisition or merger, including copies of required franchises, commission orders...

  6. Antibiotic prophylaxis in obstetric procedures.

    Science.gov (United States)

    van Schalkwyk, Julie; Van Eyk, Nancy

    2010-09-01

    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 June 2009 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. SUMMARY STATEMENTS: 1. Available evidence does not support the use of prophylactic antibiotics to reduce infectious morbidity following operative vaginal delivery. (II-1) 2. There is insufficient evidence to argue for or against the use of prophylactic antibiotics to reduce infectious morbidity for manual removal of the placenta. (III) 3. There is insufficient evidence to argue for or against the use of

  7. 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

  8. 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

  9. 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

  10. Toddler test or procedure preparation

    Science.gov (United States)

    ... a test or procedure: Explain the procedure in language your child understands, using plain words. Avoid abstract terms. Make sure your child understands the exact body part involved in the test, and that the ...

  11. 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. ...

  12. 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.

  13. 76 FR 31013 - Proposed Collection; Comment Request for Revenue Procedure 99-17

    Science.gov (United States)

    2011-05-27

    ... Revenue Procedure 99-17 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... information collection requirements related to Revenue Procedure 99-17, Mark to Market Election for.... OMB Number: 1545-1641. Revenue Procedure Number: Revenue Procedure 99-17. Abstract: This revenue...

  14. 75 FR 67165 - Proposed Collection; Comment Request for Revenue Procedure2007-XX (RP-155430-05)

    Science.gov (United States)

    2010-11-01

    ... Revenue Procedure 2007- XX (RP-155430-05) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice... soliciting comments concerning Revenue Procedure 2007-XX (RP-155430-05), Section 6707/6707A Accelerated... Procedure 2007-XX (RP-155430-05). Abstract: The collection of information this revenue procedure requires is...

  15. 42 CFR 433.320 - Procedures for refunds to CMS.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Procedures for refunds to CMS. 433.320 Section 433... Overpayments to Providers § 433.320 Procedures for refunds to CMS. (a) Basic requirements. (1) The agency must refund the Federal share of overpayments that are subject to recovery to CMS through a credit on its...

  16. 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.

  17. 48 CFR 432.003 - Simplified acquisition procedures financing.

    Science.gov (United States)

    2010-10-01

    ... procedures financing. 432.003 Section 432.003 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 432.003 Simplified acquisition procedures financing. (a) The chief of the contracting office may approve contract financing on a contract to be...

  18. 48 CFR 1332.003 - Simplified acquisition procedures financing.

    Science.gov (United States)

    2010-10-01

    ... procedures financing. 1332.003 Section 1332.003 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 1332.003 Simplified acquisition procedures financing. Contract financing may be provided for purchases made under the authority of FAR Part 13. Contract...

  19. 48 CFR 1532.003 - Simplified acquisition procedures financing.

    Science.gov (United States)

    2010-10-01

    ... procedures financing. 1532.003 Section 1532.003 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 1532.003 Simplified acquisition procedures financing. (a) Scope. This subpart provides for authorization of advance and interim payments on...

  20. 17 CFR 270.30a-3 - Controls and procedures.

    Science.gov (United States)

    2010-04-01

    ... and procedures, within the 90-day period prior to the filing date of each report on Form N-CSR (§§ 249... to be disclosed by the investment company on Form N-CSR (§§ 249.331 and 274.128 of this chapter) and... include, without limitation, controls and procedures designed to ensure that information required to be...

  1. Knowledge of Legally Sanctioned Discipline Procedures by School Personnel.

    Science.gov (United States)

    Hillman, Susan J.

    Principals, teachers, and counselors in 15 Indiana high schools were interviewed to determine what procedures they believed were required in various disciplinary actions, and what authority they believed had sanctioned these procedures. The interviewees came from small, medium, and large schools in rural and urban settings. Nearly 71 percent of…

  2. 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.

  3. 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). ...

  4. 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...

  5. 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 ...

  6. 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

  7. 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.

  8. Could conscious sedation with midazolam for dental procedures be ...

    African Journals Online (AJOL)

    2012-04-25

    Apr 25, 2012 ... they used CS. Minor oral surgical procedures and tooth extraction processes requiring no saline irrigation, however, ... The pre-diagnosis and related treatment plans .... accompanying tooth decay; orthodontic tooth extractions.

  9. 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...

  10. 45 CFR 1634.12 - Emergency procedures and waivers.

    Science.gov (United States)

    2010-10-01

    ... COMPETITIVE BIDDING FOR GRANTS AND CONTRACTS § 1634.12 Emergency procedures and waivers. The President of the... requirements imposed by law on the awards of grants and contracts for a particular fiscal year. ...

  11. Application of safeguards procedures

    International Nuclear Information System (INIS)

    1977-01-01

    The earliest applications of safeguards procedures took place in a political and technical climate far different from that of today. In the early 1960's there was a fear of the proliferation possibilities which could arise as more and more countries acquired nuclear power plants. Today nuclear power is being produced in some 20 countries without resulting in nuclear weapons proliferation. The export of equipment and technology for the nuclear fuel cycle, however, has become the subject of current concern. In view of these developments, it is not surprising that techniques in the application of safeguards have also changed. In order to appreciate the nature of these changes, it is important to be aware of the original general attitude towards the technical problems of safeguards applications. Originally, the common attitude was that the objectives of safeguards were self-evident and the methods, while in need of development, were known at least in outline. Today, it has become evident that before a safeguards procedure can be applied, the objectives must first be carefully defined, and the criteria against which success in meeting those objectives can be measured must also be developed. In line with this change, a significant part of the effort of the safeguards inspectorate is concerned with work preliminary and subsequent to the actual inspection work in the field. Over the last two years, for example, a considerable part of the work of experienced safeguards staff has been spent in analysing the possibilities of diverting material at each facility to be safeguarded. These analyses are carried out in depth by a 'facility officer' and are subjected to constructive criticism by teams composed of staff responsible for similar types of facilities as well as other technical experts. The analyses consider the measures currently considered practicable, to meet the diversion possibilities and where necessary list the development work needed to overcome any present

  12. Human Engineering Procedures Guide

    Science.gov (United States)

    1981-09-01

    Research Laboratory AFETR Air Force Eastern Test Range AFFTC Air Force Flight Test Center AFHRL Air Force Human Resources Laboratory AFR Air Force...performance requirements through the most effective use of man’s performance capability. 13 Human Engineering is one of five elements in the Human...applied judiciously and tailored to fit * the program or program phase and the acquisition strategy to achieve cost effective acquisition and life cycle

  13. 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

  14. 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.

  15. Informed consent: not just for procedures anymore.

    Science.gov (United States)

    Feld, Andrew D

    2004-06-01

    The ethical and legal requirement to obtain informed consent prior to performing a procedure or administering a treatment derives from the concept of personal (patient) autonomy. The competent patient, after receiving appropriate disclosure of the material risks of the procedure or treatment, understanding those risks, the benefits, and the alternative approaches, makes a voluntary and uncoerced informed decision to proceed. This article will present a general overview of the modern concept of informed consent as a process (mutual communication) rather than an event (document signing). The historical evolution of this concept and the legal rulings that have shaped the requirements of informed consent will be cited. The benefits of informed decision making as a communication and risk management tool are presented. This review is intended as general information, and not as legal advice, which should be sought from a health-care attorney.

  16. 75 FR 78804 - Proposed Collection; Comment Request for Revenue Procedure 2003-45 and Revenue Procedure 2004-48

    Science.gov (United States)

    2010-12-16

    ... required by the Paperwork Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently... Corporations, and Revenue Procedure 2004-48, Deemed Corporate Election for Late Electing S Corporations. DATES...-45, Late Election Relief for S Corporations, and Revenue Procedure 2004-48, Deemed Corporate Election...

  17. 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

  18. 76 FR 44656 - Proposed Collection; Comment Request for Revenue Procedure(s)

    Science.gov (United States)

    2011-07-26

    ... disaffililiation and procedure to eliminate impediments to e-filing consolidated returns and reduce reporting... Eliminate Impediments to E-Filing Consolidated Returns and Reduce Reporting Requirements. OMB Number: 1545... eliminate impediments to the electronic filing of Federal income tax returns (e- filing) and to reduce the...

  19. Radiation dose during angiographic procedures

    International Nuclear Information System (INIS)

    Lavoie, Ch.; Rasuli, P.

    2001-01-01

    The use of angiographic procedures is becoming more prevalent as new techniques and equipment are developed. There have been concerns in the scientific community about the level of radiation doses received by patients, and indirectly by staff, during some of these radiological procedures. The purpose of this study was to assess the level of radiation dose from angiographic procedures to patient at the Ottawa Hospital, General Campus. Radiation dose measurements, using Thermo-Luminescent Dosimeters (TLDs), were performed on more than 100 patients on various procedures. The results show that while the patient dose from the great majority of angiographic procedures is less than 2 Gy, a significant number of procedures, especially interventional procedures may have doses greater than 2 Gy and may lead to deterministic effects. (author)

  20. Autonomous Real Time Requirements Tracing

    Science.gov (United States)

    Plattsmier, George; Stetson, Howard

    2014-01-01

    One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto- Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner-TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the

  1. 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

  2. Diesel generator trailer acceptance test procedure

    International Nuclear Information System (INIS)

    Kostelnik, A.J.

    1994-01-01

    This Acceptance Test Procedure (ATP) will document compliance with the requirements of WHC-S-0252 Rev. 1 and ECNs 609271, and 609272. The equipment being tested is a 150KW Diesel Generator mounted on a trailer with switchgear. The unit was purchased as a Design and Fabrication procurement activity. The ATP was written by the Seller and will be performed by the Seller with representatives of the Westinghouse Hanford Company witnessing the test at the Seller's location

  3. 29 CFR 15.26 - Claims procedures.

    Science.gov (United States)

    2010-07-01

    ... forth in § 15.21(d) will be accepted and considered a claim under the Act if it constitutes a demand for compensation from the Department. A demand is not required to be for a specific sum of money. (c) Notification... 29 Labor 1 2010-07-01 2010-07-01 true Claims procedures. 15.26 Section 15.26 Labor Office of the...

  4. Administrative Procedure Act and mass procedures (illustrated by the nuclear licensing procedure)

    International Nuclear Information System (INIS)

    Naumann, R.

    1977-01-01

    The report deals with the administrative procedure law of 25.5.76 of the Fed. Government, esp. with its meaning for the administrative procedures for the permission for nuclear power plants, as fas ar so-called mass procedures are concerned. (UN) [de

  5. Method Validation Procedure in Gamma Spectroscopy Laboratory

    International Nuclear Information System (INIS)

    El Samad, O.; Baydoun, R.

    2008-01-01

    The present work describes the methodology followed for the application of ISO 17025 standards in gamma spectroscopy laboratory at the Lebanese Atomic Energy Commission including the management and technical requirements. A set of documents, written procedures and records were prepared to achieve the management part. The technical requirements, internal method validation was applied through the estimation of trueness, repeatability , minimum detectable activity and combined uncertainty, participation in IAEA proficiency tests assure the external method validation, specially that the gamma spectroscopy lab is a member of ALMERA network (Analytical Laboratories for the Measurements of Environmental Radioactivity). Some of these results are presented in this paper. (author)

  6. Principles and procedures in forensic toxicology.

    Science.gov (United States)

    Wyman, John F

    2012-09-01

    The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

  7. Procedure for reducing hydrogen ion concentration in acidic anion eluate

    International Nuclear Information System (INIS)

    Parobek, P.; Baloun, S.; Plevac, S.

    1992-01-01

    A procedure is suggested for reducing the concentration of hydrogen ions in the acidic anionic eluate formed during the separation of uranium. The procedure involves anex elution, precipitation, filtration, precipitate rinsing, and anex rinsing. The procedure is included in the uranium elution process and requires at least one ion exchanger column and at least one tank in the continuous or discontinuous mode. Sparing the neutralizing agent by reducing the hydrogen ion concentration in the acidic anionic eluate is a major asset of this procedure. (Z.S.). 1 fig

  8. 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.

  9. Bioequivalence evaluation of new microparticulate capsule and ...

    African Journals Online (AJOL)

    data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann's two one-sided t-test ... The reasons for low compliance of NSAIDs ... 7.32 cm (range, 168.2 - 190.93 cm); and BMI, ... blood pressure and body temperature) were ... Figure 1: Scanning electron microscopy image of AF-7 microparticles.

  10. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad; Akrawi, Sabah H; Tolley, Luke T; Sioud, Salim H; Zaater, Mohammed F; Emwas, Abdul-Hamid M

    2011-01-01

    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

  11. 9 CFR 442.2 - Definitions and procedures for determining net weight compliance.

    Science.gov (United States)

    2010-01-01

    ... POULTRY PRODUCTS INSPECTION ACT QUANTITY OF CONTENTS LABELING AND PROCEDURES AND REQUIREMENTS FOR ACCURATE... Dressing 3.7Pressed and Blown Glass Tumblers and Stemware 3.8Volumetric Test Procedures for Paint, Varnish...

  12. 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...

  13. 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 ...

  14. 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)

  15. 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

  16. 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

    2014-04-11

    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.

  17. Chromatographic monitoring procedures in laboratory practice

    Energy Technology Data Exchange (ETDEWEB)

    Kaplina, E G; Belova, O I; Lasunina, N A

    1976-01-01

    The Moscow Coke and Chemical Works consist of three plants in combination, viz., the coking plant, the synthetic ammonia plant using coke-oven-gas hydrogen and the oxygen plant. The plant requirements include daily analyses not only of the coke-oven gas but also of a rich gas and an ethylene fraction. The analyses are carried out in VTI-2 apparatus. The analytical data are used to calculate the calorific values and densities of the gases. The time requirements are very considerable and the laboratory has long been engaged in developing and introducing chromatographic procedures for the major constituents of coke-oven gas, rich gas and ethylene fraction. The procedure developed for the coke-oven and rich gases uses two parallel columns, one packed with molecular sieves and the other with grade KSM silica gel. Hydrogen was determined with argon as the carrier gas, and all other constituents with helium. The procedure was time-consuming and complicated. An attempt was made to separate the gases in an LKhM-7a chromatograph with a programme-controlled 50 to 250/sup 0/C heating cycle, but the procedure still had a number of serious defects and could not be recommended for regular quality control. The final variant involved two parallel columns and a procedure based on that in GOST 14920 (''Dry gas. Proximate analysis''). The chromatograph was a type KhL-69 with a 6-way cock in the gas line so that each of the columns could be brought on stream in succession. The analytical column packings were zeolite (in a 2 m column) and diatomaceous brick with 25% n-hexadecane (in a 6 m column).

  18. 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)

  19. Aesthetic procedures in office practice.

    Science.gov (United States)

    Small, Rebecca

    2009-12-01

    Since the approval of botulinum toxin, dermal fillers, and lasers for cosmetic use, minimally invasive aesthetic procedures have rapidly become the treatments of choice for age-related facial changes. In the past 10 years, aesthetic procedures have increased nearly five-fold. Of the 10.2 million aesthetic treatments performed in 2008, 83 percent were minimally invasive procedures. Botulinum toxin and dermal filler injections, laser hair reduction, chemical peels, laser skin resurfacing, microdermabrasion, and intense pulsed light photorejuvenation were the most commonly performed procedures in 2008. These procedures are effective and associated with minimal discomfort, and they have a low incidence of adverse effects and short recovery times. High patient and physician satisfaction have contributed to their growing popularity and availability in the primary care setting. As patient demand for aesthetic treatments increases, family physicians should be familiar with common minimally invasive aesthetic procedures when advising patients or incorporating aesthetic care into office practice.

  20. Procedure of safe handling with cytostatic drugs

    Directory of Open Access Journals (Sweden)

    Kodžo Dragan

    2003-01-01

    Full Text Available Working group for safe handling with cytostatic drugs has been formed by the Ministry of Health, and it consists of professionals from IORS, Federal Bureau of Weights and Measures, Industrial Medicine, Institute of Hematology, Military Medical Academy, and Crown Agents. The aim of this working group is to prepare procedures for safe handling with cytostatic drugs, as well as program for educational seminar for nurses, medical technicians, and pharmaceutical technicians. The procedures will serve as a guide of good practice of oncology health care, and will refer to all actions that health care professionals carry out from the moment of drugs arrival to the pharmacy to the moment of their application. In the first segment of this procedure, general rules are given for working with cytotoxic agents, control for risky exposures, safe system of work, control of working environment, monitoring of the employees' health condition adequate protection in the working environment, protective equipment of the employees (gloves, mask, cap, eyeglasses, shoe covers, coats and chambers for vertical laminary air stream. Storing of cytostatics, procedure in case of accident, and waste handling and removal are also described in this segment. Fifty-three standard operational procedures are described in detail in the second segment. Training scheme for preparation of chemotherapy is given in the third segment - education related to various fields and practical part, which would be carried out through workshops, and at the end of the course participants would pass a test and obtain certificate. After the procedures for safe handling with cytostatics are legally regulated employer will have to provide minimum of protective equipment, special rooms for the drugs dissolving, chambers with laminar airflow, 6 hours working time, rotation of the staff working with drugs dissolving in intervals of every five years, higher efficiency, better health control. In conclusion

  1. Characteristics of Mobile Payment Procedures

    OpenAIRE

    Kreyer, Nina; Pousttchi, Key; Turowski, Klaus

    2002-01-01

    Companies are not going to invest into the development of innovative applications or services unless these can be charged for appropriately. Thus, the existence of standardized and widely accepted mobile payment procedures is crucial for successful business-to-customer mobile commerce. The acceptance of mobile payment procedures depends on costs, security and convenience issues. For the latter, it is important that a procedure can be used over the different payment scenarios mobile commerce, ...

  2. Coding for urologic office procedures.

    Science.gov (United States)

    Dowling, Robert A; Painter, Mark

    2013-11-01

    This article summarizes current best practices for documenting, coding, and billing common office-based urologic procedures. Topics covered include general principles, basic and advanced urologic coding, creation of medical records that support compliant coding practices, bundled codes and unbundling, global periods, modifiers for procedure codes, when to bill for evaluation and management services during the same visit, coding for supplies, and laboratory and radiology procedures pertinent to urology practice. Detailed information is included for the most common urology office procedures, and suggested resources and references are provided. This information is of value to physicians, office managers, and their coding staff. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. 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...

  4. 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.

  5. 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)

  6. Transthoracic Adrenal Biopsy Procedure Using Artificial Carbon Dioxide Pneumothorax as Outpatient Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Favelier, Sylvain [CHU (University Hospital), Department of Radiology (France); Guiu, Severine [Georges-Francois Leclerc Cancer Center, Department of Oncology (France); Cherblanc, Violaine; Cercueil, Jean-Pierre; Krause, Denis; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr [CHU (University Hospital), Department of Radiology (France)

    2013-08-01

    Many routes have been described for percutaneous adrenal gland biopsy. They require either a complex non-axial path or a long hydrodissection or even pass through an organ thereby increasing complications. We describe here an approach using an artificially-induced carbon dioxide (CO{sub 2}) pneumothorax, performed as an outpatient procedure in a 57-year-old woman. Under local anaesthesia, 200 ml of CO{sub 2} was injected in the pleural space through a Veress needle under computed tomography fluoroscopy, to clear the lung parenchyma from the biopsy route. Using this technique, transthoracic adrenal biopsy can be performed under simple local anaesthesia as an safely outpatient procedure.

  7. Avoiding Psychological Pitfalls in Aesthetic Medical Procedures.

    Science.gov (United States)

    Wang, Qiuyu; Cao, Chuan; Guo, Rui; Li, Xiaoge; Lu, Lele; Wang, Wenping; Li, Shirong

    2016-12-01

    Dr. Cash's result given in Table 4 (p aesthetic patients diagnosed with BDD after aesthetic procedures lasting one month. There was a high prevalence rate (14.2 %) of body dysmorphic disorder in aesthetic procedure seekers, and it seemed that those patients suffering from BDD were more likely to be dissatisfied with the results of the aesthetic medical procedures. However, general aesthetic patients showed improvement in most assessments which indicated that aesthetic medical procedures could not only enhance patient appearance, but also patient low self-esteem and QoL. Self-satisfaction could also be promoted. A screening procedure for BDD including suitable screening questionnaires might be considered for routine use in aesthetic clinical settings to minimize dissatisfaction and complaints. This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

  8. Procedures for Sensitive Immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Givol, D. [Department of Chemical Immunology, Weizmann Institute of Science, Rehovot (Israel)

    1970-02-15

    Sensitive immunoassay methods should be applied to small molecules of biological importance, which are non-immunogenic by themselves, such as small peptide hormones (e.g. bradykinin), plant hormones (e.g. indoleacetic acid), nucleotides and other small molecules. Methods of binding these small molecules, as haptens, to immunogenic carriers by various cross-linking agents are described (dicyclohexylcarbodiimide, tolylene-diisocyanate and glutaraldehyde), and the considerations involved in relation to the methods of binding and the specificity of the antibodies formed are discussed. Some uses of antibody bound to bromoacetyl cellulose as an immuno adsorbent convenient for assay of immunoglobulins are described. Finally, the sensitive immunoassay method of chemically modified phage is described. This includes methods of binding small molecules (such as the dinitrophenyl group, penicillin, indoleacetic acid) or proteins (such as insulin, immunoglobulins) to phages. Methods of direct chemical conjugation, or an indirect binding via anti-phage Fab, are described. The phage inactivation method by direct plating and its modifications (such as decision technique and complex inactivation) are compared with the more simple end-point titration method. The inhibition of phage inactivation has some advantages as it does not require radioactive material, or expensive radioactive counters, and avoids the need for separation between bound and unbound antigen. Hence, if developed, it could be used as an alternative to radioimmunoassay. (author)

  9. 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 readability guidelines for patient materials of 6th grade (p 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.

  10. A procedure for effective Dancoff factor calculation

    International Nuclear Information System (INIS)

    Milosevic, M.

    2001-01-01

    In this paper, a procedure for Dancoff factors calculation based on equivalence principle and its application in the SCALE-4.3 code system is described. This procedure is founded on principle of conservation of neutron absorption for resolved resonance range in a heterogeneous medium and an equivalent medium consisted of an infinite array of two-region pin cells, where the presence of other fuel rods is taken into account through a Dancoff factor. The neutron absorption in both media is obtained using a fine-group elastic slowing-down calculation. This procedure is implemented in a design oriented lattice physics code, which is applicable for any geometry where the method of collision probability is possible to apply to get a flux solution. Proposed procedure was benchmarked for recent exercise that represents a system with a fuel double heterogeneity, i.e., fuel in solid form (pellets) surrounded by fissile material in solution, and for a 5x5 irregular pressurised water reactor assembly, which requires different Dancoff factors. (author)

  11. Postoperative infections in craniofacial reconstructive procedures.

    Science.gov (United States)

    Fialkov, J A; Holy, C; Forrest, C R; Phillips, J H; Antonyshyn, O M

    2001-07-01

    The rate of, and possible risk factors for, postoperative craniofacial infection is unclear. To investigate this problem, we reviewed 349 cases of craniofacial skeletal procedures performed from 1996 to 1999 at our institution. Infection rate was determined and correlated with the use of implants, operative site, and cause of deformity. The inclusion criteria consisted of all procedures requiring autologous or prosthetic implantation in craniofacial skeletal sites, as well as all procedures involving bone or cartilage resection, osteotomies, debridement, reduction and/or fixation. Procedures that did not involve bone or cartilage surgery were excluded. The criteria for diagnosis of infection included clinical confirmation and one or more of 1) intravenous or oral antibiotic treatment outside of the prophylactic surgical regimen; 2) surgical intervention for drainage, irrigation, and or debridement; and 3) microbiological confirmation. Among the 280 surgical cases that fit the inclusion criteria and had complete records, there were 23 cases of postoperative infection (8.2%). The most common site for postoperative infection was the mandible (infection rate = 16.7%). Multiple logistic regression analysis revealed gunshot wound to be the most significant predictor of postoperative infection. Additionally, porous polyethylene implantation through a transoral route was correlated with a significant risk of postoperative infection.

  12. 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

  13. 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

  14. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    of Hartmann's procedure as safely as in open surgery and with a faster recovery, shorter hospital stay and less blood loss despite a longer knife time. It therefore seems reasonable to offer patients a laparoscopic procedure at departments which are skilled in laparoscopic surgery and use it for standard...

  15. Developing Competency in Payroll Procedures

    Science.gov (United States)

    Jackson, Allen L.

    1975-01-01

    The author describes a sequence of units that provides for competency in payroll procedures. The units could be the basis for a four to six week minicourse and are adaptable, so that the student, upon completion, will be able to apply his learning to any payroll procedures system. (Author/AJ)

  16. 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...

  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. 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

  19. Process & Quality procedures for transport & handling activities

    CERN Document Server

    Böttcher, O

    2002-01-01

    To respect the detailed and complex planning of the LHC installation project it is essential to reduce possible faults in every technical service that can cause delays in the schedule. In order to ensure proper execution of transport and handling activities it is important to get detailed information from the clients as early as possible in order to do the planning and the organisation of the required resources. One procedure that requires greater focus in the future is the preparation of the resources. The goal is to prevent equipment breakdowns and accidents while executing transport and handling activities. In the LEP dismantling project multiple breakdowns of important cranes caused serious problems in the project schedule. For the LHC installation project similar incidents in the reliability of the equipment cannot be accepted because of the high sensitivity of the whole schedule. This paper shall outline the efforts and methods that are put in place in order to meet the LHC installation requirements.

  20. 7 CFR 1753.8 - Contract construction procedures.

    Science.gov (United States)

    2010-01-01

    ... of all bids including “Buy American” evaluations, if any, and all other evaluations required by law... Contract construction procedures. (a) Sealed, competitive bidding—(1) Bid opening date. The borrower is responsible for scheduling the bid opening date. If RUS review of P&S is required by § 1753.7, the borrower...

  1. Biomonitoring test procedures and biological criteria

    Energy Technology Data Exchange (ETDEWEB)

    Kszos, L.A. [Oak Ridge National Lab., TN (United States); Lipschultz, M.J. [City of Las Vegas, NV (United States); Foster, W.E. [Saint Mary`s Coll., Winona, MN (United States)

    1997-10-01

    The Water Environment Federation recently issued a special publication, Biomonitoring in the Water Environment. In this paper, the authors highlight the contents of the chapter 3, Biomonitoring Test Procedures, identify current trends in test procedures and introduce the concept of biological criteria (biocriteria). The book chapter (and this paper) focuses on freshwater and marine chronic and acute toxicity tests used in the National Pollutant Discharge Elimination System (NPDES) permits program to identify effluents and receiving waters containing toxic materials in acutely or chronically toxic concentrations. The two major categories of toxicity tests include acute tests and chronic tests. The USEPA chronic tests required in NPDEs permits have been shortened to 7 days by focusing on the most sensitive life-cycle stages; these tests are often referred to as short-term chronic tests. The type of test(s) required depend on NPDES permit requirements, objectives of the test, available resources, requirements of the test organisms, and effluent characteristics such as variability in flow or toxicity. The permit writer will determine the requirements for toxicity test(s) by considering such factors as dilution, effluent variability, and exposure variability. Whether the required test is acute or chronic, the objective of the test is to estimate the safe or no effect concentration which is defined as the concentration which will permit normal propagation of fish and other aquatic life in the receiving waters. In this paper, the authors review the types of toxicity tests, the commonly used test organisms, and the uses of toxicity test data. In addition, they briefly describe research on new methods and the use of biological criteria.

  2. 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)

  3. 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.

  4. Procedure for Electronic Management of Rulemaking and Other Docketed Records in the Federal Docket Management System

    Science.gov (United States)

    This procedure identifies the specific requirements, processes and supporting documents EPA uses to electronically manage rulemaking and other docketed records in the Federal Docket Management System (FDMS).

  5. Biomass Compositional Analysis Laboratory Procedures | Bioenergy | NREL

    Science.gov (United States)

    Biomass Compositional Analysis Laboratory Procedures Biomass Compositional Analysis Laboratory Procedures NREL develops laboratory analytical procedures (LAPs) for standard biomass analysis. These procedures help scientists and analysts understand more about the chemical composition of raw biomass

  6. 15 CFR 911.8 - Technical requirements.

    Science.gov (United States)

    2010-01-01

    ... PROCEDURES CONCERNING USE OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.8 Technical requirements. (a) All platform operators of the NOAA DCS must use a data collection platform radio set whose technical... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Technical requirements. 911.8 Section...

  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. 42 CFR 3.106 - Security requirements.

    Science.gov (United States)

    2010-10-01

    ... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT PSO Requirements and Agency Procedures § 3.106 Security requirements. (a) Application. A PSO must secure patient safety work product in conformance with the security... the confidentiality and security of patient safety work product. (2) Distinguishing patient safety...

  9. European Utility Requirements: European nuclear energy

    International Nuclear Information System (INIS)

    Komsi, M.; Patrakka, E.

    1997-01-01

    The work procedure and the content of the European Utility Requirements (EUR) concerning the future LWRs is described in the article. European Utility Requirements, produced by utilities in a number of European countries, is a document specifying the details relating to engineered safety, operating performance, reliability and economics of the reactors to be built by manufacturers for the European market

  10. 12 CFR 370.9 - Recordkeeping requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Recordkeeping requirements. 370.9 Section 370.9 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY TEMPORARY LIQUIDITY GUARANTEE PROGRAM § 370.9 Recordkeeping requirements. The FDIC will establish procedures...

  11. 12 CFR 404.4 - Request requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Request requirements. 404.4 Section 404.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.4 Request requirements. (a) Form. Requests...

  12. 24 CFR 511.11 - Project requirements.

    Science.gov (United States)

    2010-04-01

    ... low income occupancy or rent projections, or restrictions on return on investment or other similar policies that prevent an owner, whether for-profit or non-profit, from maximizing return or setting rent... requirements and with the affirmative marketing requirements and procedures adopted under § 511.13, for the...

  13. 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...

  14. Simplified Laboratory Runoff Procedure (SLRP): Procedure and Application

    National Research Council Canada - National Science Library

    Price, Richard

    2000-01-01

    The Simplified Laboratory Runoff Procedure (SLRP) was developed to provide a faster, less expensive approach to evaluate surface runoff water quality from dredged material placed in an upland environment...

  15. Pelvic denervation procedures for dysmenorrhea.

    Science.gov (United States)

    Ramirez, Christina; Donnellan, Nicole

    2017-08-01

    Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

  16. 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...

  17. Piezometer installation and monitoring procedure: Revision 1

    International Nuclear Information System (INIS)

    1987-04-01

    The Deaf Smith County (Texas) site has been selected by the US Department of Energy as one of three candidate sites for characterization to determine its suitability as a geologic repository for high-level nuclear waste. The installation and monitoring of piezometers has been identified as one of the tasks required during the development of an underground Exploratory Shaft Facility to satisfy specific information needs through a program of in situ testing, instrumentation and monitoring. The scope of piezometer installation and monitoring encompasses the installation of fluid pressure measuring equipment and the subsequent collection, presentation and interpretation of piezometric data from strata surrounding the Exploratory Shaft Facility (ESF) prior to, during and following construction of the ESF, and as part of geohydrologic testing within the ESF. This procedure describes the required instrumentation, equipment, and sequence of activities for piezometer installation in the ESF. The procedure also includes details on the data recording and presentation requirements, personnel responsibilities, test management and quality assurance. 16 refs., 12 figs., 2 tabs

  18. 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.

  19. 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

  20. FREY’S PROCEDURE- TO ANALYSE THE OUTCOME OF THIS PROCEDURE IN CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Shilpa Mariappa Casaba

    2017-04-01

    Full Text Available BACKGROUND Chronic Pancreatitis (CP is a progressive inflammatory disease characterised by debilitating pain and pancreatic insufficiency. There is enormous personal and socio-economic impact on impairment of quality of life, inability to work and even shortening of life expectancy. Although, pancreaticoduodenectomy had been considered the standard surgical procedure for patients with CP because of its high post-op complications with exocrine and endocrine insufficiency, it is not preferred. This has led to a hybrid procedure described by Frey’s, which is used in our study for CP. We aim to analyse the short-term and long-term outcomes of Frey’s procedure at a tertiary care center in patients with chronic pancreatitis. MATERIALS AND METHODS A retrospective review of all CP patients who underwent Frey procedure were reviewed from January 2007-January 2016. Perioperative variables, short-term (30 days and long-term (3 years outcomes were reviewed. Data are frequency (% or mean. RESULTS A total of 97 patients underwent Frey’s procedure. A total of 72 (70.7% were men and 25 (29.3% were women. Mean age was 38 years (range 14-66 years. Indications for surgery included intractable pain (n=97, 100% and obstructive jaundice (n=4, 4.3%. 9 patients (32.6% were diabetic preoperatively. Concomitant procedures include biliary drainage procedure was done for 4 patients (4.3%, i.e. choledochojejunostomy and splenectomy for 2 patients (2.1%, cholecystectomy (n=6, 6%. Short-term outcomes include surgical site infection (n=10, 10%, pancreatic leak (n=6, 5.82% and 2 patients required reoperation for bleeding and no mortality (30 days, diabetic ketoacidosis (n=2, 2%. Pancreatic carcinoma was detected in 3 (2.1% patients. Long-term outcomes include pain free status (n=80, 86.9%, median follow-up of 3 years. Redo pancreatic procedure was performed in 1 (4.3% for anastomotic leak. CONCLUSION Frey’s procedure is a safe and effective pain palliative option for CP