Statistical analysis of bioequivalence studies school of statistics and actuarial science by mavuto nyathi. Portions of this section were transferred to the guidance on the conduct and analysis of comparative bioavailability studies since the information was more relevant to study design than to standards. Section 4 presents some controversial issues that are commonly encountered when conducting bioequivalence studies for the assessment of. Design and analysis of bioavailability and bioequivalence studies, 2nd edn. Included are timely updates on many controversial and newly emerging areas in the design and analysis of bioavailability and bioequivalence studies. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Taking into account the regulatory and scientific developments that have occurred since the second edition, design and analysis of bioavailability and bioequivalence studies, third edition provides a complete presentation of the latest progress of activities and results in bioavailability and bioequivalence on regulatory requirements, scientific. Designs of bioavailability studies statistical inferences for effects from a standard 2x2 crossover design statistical methods for average bioavailability power and sample size determination transformation and analysis of individual subject ratios the assessment of inter and intrasubject variabilities. Buy design and analysis of bioavailability and bioequivalence studies 9781584886686. Average, population and individual bioequivalence is checked. Bioavailability and bioequivalence studies submitted in ndas or inds general considerations. Dissolution bioavailability bioequivalence download ebook. Bioavailability and bioequivalence studies are required to ensure therapeutic equivalence between a pharmaceutically equivalent test drug and a generic drug or reference drug.
The assessment of be of different drug products is based on the fundamental assumption that two products are equivalent when the rate and extent of absorption of the test drug does not show a significant difference from the rate and extent of absorption of the reference drug when administered at the same molar dose of the therapeutic ingredient under similar. It involved sample size reestimation at an interim time point using an abba crossover design. Preeminent experts update a wellrespected booktaking into account the regulatory and scientific developments that have occurred since the second edition, design and analysis of bioavailability and bioequivalence studies, third edition provides a complete presentation of the latest progress of activities and results in bioavailability and bioequiva. Bioavailability and bioequivalence studies intechopen. Taking into account the regulatory and scientific developments that have occurred since the second edition, design and analysis of bioavailability and bioequivalence studies, third edition provides a complete presentation of the latest progress of activities and results in bioavailability and bioequivalence on regulatory. Tasneem ahmad, cbsbr, university of karachi 1 selection of be study design estimation of sample size number of volunteers 800 calculation of bioavailability ba.
This practical referencetext, written at a basic mathematical and statistical level, presents important statistical concepts for assessing bioequivalence through real examples and provides a thorough, unified discussion of the design and analysis of bioavailability and bioequivalence studies. The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase tk encoded by hsv and vzv. Transformation and analysis of individual subject ratios 7. In bioavailabilitybioequivalence studies, following the administration of a drug.
Statistical inference for effects from a standard 2x2 crossover design ii average bioequivalence 4. To every method there are numerical examples given with real data. To see whether tablet a is bioequivalent to tablet b, the bioavailability rates of the two are compared. Provides a comprehensive summary of the continuously growing literature and research activities on the regulatory requirements, scientific and practical issues, and statistical methodology of the design and analysis of bioavailability and bioequivalence studies. This study is required for all immediaterelease and modifiedrelease oral dosage forms. The design and evaluation of wellcontrolled bioequivalence studies require cooperative input from pharmacokineticists, statisticians, clinicians, bioanalytical chemists, and others. In the next section, the design and analysis of bioequivalence studies will be briefly outlined. Provides a complete presentation of the latest progress of activities and results in bioavailability and bioequivalence on regulatory requirements. Design and analysis of bioavailability and bioequivalence studies third edition, shein. Nevertheless this book is a fantastic reference for bioavailability and bioequivalence and is definitely worth having.
This draft guidance is a revision of an october 1997 draft guidance entitled foodeffect bioavailability and bioequivalence studies. Bioequivalence and bioavailability studies are important during drug development of both new drug products. The purpose of this study was to evaluate the effect of residual variability and carryover on average bioequivalence abe studies performed under a 2. Design and analysis of bioavailability and bioequivalence studies sheinchung chow, jenpei liu it has been over 9 years since the second edition of this book came out. Establishing bioequivalence comparative pharmacokinetic studies in vivo comparative bioavailability studies comparison of performance of products based rate and extent of absorption of drug substance from each formulation area under the concentrationtime curve auc maximal concentration cmax time to maximal concentration. Generics and bioequivalence provides a clear, insightful, and indepth analysis of the many complex issues encountered in the determination of drug bioequivalence.
Primary stages of development of a suitable dosage form for a new drug entity. Bioavailability and bioequivalence wiley online library. Bioavailability studies submitted in ndas or inds general considerations february 2019. Experimental design and analysis for bioequivalence trials by p. View enhanced pdf access article on wiley online library html view. Dissolution bioavailability bioequivalence download. Draft guidance for industry on foodeffect bioavailability. In what follows, the assumption that relative bioavailability is predictive of clinical outcomes, criteria for bioequivalence, basic considerations for conduct of a bioequivalence study such as study design, sample size, and statistical methods, current issues including onesizefitsall criterion and drug interchangeability, and recent. Drug interchangeability in terms of drug prescribability and drug switchability are discussed in section 3. Fasting study bioequivalence studies are usually evaluated by a single dose, twoperiod, twotreatment, twosequence, openlabel, randomized crossover design comparing equal doses of the test and reference products in fasted, adult, healthy subjects.
Bibliography includes bibliographical references and index. Experimental design and analysis for bioequivalence trials. Failure of statistical methods to prove bioequivalence of meloxicam drug products. Ensuring uniformity in standards of quality, efficacy, and safety of pharmaceutical products is the fundamental responsibility of central drugs standard control. Request pdf on mar 1, 2003, minge xie and others published design and analysis of bioavailability and bioequivalence studies. Design and analysis of bioavailability and bioequivalence. I did such a twostage design while working at auxilium. Design and analysis of bioavailability and bioequivalence studies, 3rd edition by chow, sc. The scientific questions to be answered, the nature of the. In the following sections, requirements for the design and conduct of bioavailability or bioequivalence studies are formulated.
Fda is announcing the availability of a draft guidance for industry entitled foodeffect bioavailability and fed bioequivalence studies. Design and analysis of bioavailability and bioequivalence studies. This document is intended to provide guidance for the design and analysis of in vivo bioequivalence studies. This study was undertaken to show the existence of bioequivalence in drugs. Bioavailability and bioequivalence studies submitted in. The greater antiviral activity of acyclovir against hsv. Conduct and analysis of bioavailability and bioequivalence studies. In 127 generic drugs applications to the us food and drug administration in 1997 the mean difference was 3. In a simple parallel study design, the statistical analysis should be conducted including the betweensubject variability to calculate the 90% confidence interval of the treatment mean difference. Bioequivalence studies are often part of applications for generic veterinary. In this regard bioequivalence studies investigating the di erence between two treatment.
Bioavailability is considered in generic drugs to ensure. Bioequivalence and bioavailability, pre conference workshop budapest, 11 may 2009 1 69 57 statistical design and analysis i informa life scienceslife sciences statistical design and analysis i helmut schutz bebac consultancy services for bioequivalence and bioavailability studies 1070 vienna, austria helmut. The assessment of inter and intrasubject variabilities 8. Design and analysis of bioavailability and bioequivalence studies, cap. By definition, when the drug is administered intravenously, its bioavailability is 100%. The overall design of the bioequivalence study should be based on the knowledge of the pharmacokinetics, pharmacodynamics and therapeutics of the api. Design and analysis of bioavailability and bioequivalence studies third edition. Its commonly observed that there are several formulations of the same drug, in the same dose, in similar dosage form and meant to be given by the same route. Bioavailability and bioequivalence studies for orally administered drug products general considerations. Introduction designs of bioavailability studies statistical inferences for effects from a standard 2 x 2 crossover design statistical methods for average bioavailability power and sample size determination transformation and analysis of individual subject ratios assessment of inter and intrasubject variabilities assumptions and. Presents the recent developments in methodology, including population and individual bioequivalence. Oct 04, 2015 fasting study bioequivalence studies are usually evaluated by a single dose, twoperiod, twotreatment, twosequence, openlabel, randomized crossover design comparing equal doses of the test and reference products in fasted, adult, healthy subjects.
Provides a practical overview of the design and analysis of bioequivalence studies. Oct 15, 2008 preeminent experts update a wellrespected booktaking into account the regulatory and scientific developments that have occurred since the second edition, design and analysis of bioavailability and bioequivalence studies, third edition provides a complete presentation of the latest progress of activities and results in bioavailability and bioequiva. Pharmacokinetic analysis is done using the blood or plasma concentrationtime profile. In bioequivalence studies, the study design also determines the appropriate statistical model for data analysis. The basic design for a bioequivalence study is determined by. Design and analysis of bioavailability and bioequivalence studies, third edition shein. Bioequivalence studies compare both the rate and extent of absorption of various multisource drug. Guideline for bioavailability and bioequivalence ich. Project director center for bioequivalence studies and bioassay research international center for chemical and biological sciences university of karachi pakistan. Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 hsv1, 2 hsv2 17, and varicellazoster virus vzv 8. Bioavailability and bioequivalence in drug development.
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