D1S05-Zhang-v1.2-FINAL.pdf

1、Common Bioequivalence Study Design Deficiencies and How to Avoid ThemZhen Zhang,Ph.D.Master PharmacologistDivision of Bioequivalence I(DBI)Office of Bioequivalence(OB)Office of Generic Drugs(OGD)CDER|US FDASBIA:Generic Drug Forum April 22-23,2026www.fda.gov2Learning ObjectivesUnderstand study design

2、s and relevant guidancesIdentify common deficiencies related to study design and analysisIdentify unacceptable post-hoc modifications in BE studiesApply strategies to prevent common deficiencies and improve study success ratewww.fda.gov3Types of Bioequivalence(BE)Studies In vivo BE Studies In vivo p

3、harmacokinetic(PK)BE study In vivo pharmacodynamic(PD)BE study In vivo comparative clinical endpoint study In vitro BE Studies In vitro release test In vitro permeation test Particle size distribution test Single actuation content test Many othersApproximately 50%of ANDAs submitted over the past 12

4、years included one or more PK BE studieswww.fda.gov4Guidances for in vivo PK BE Study DesignGeneral GuidanceFDA Guidance for Industry:Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application(August 2021)FDA PK BE GuidanceICH M13A Bioequivale

5、nce for Immediate-Release Solid Oral Dosage Forms(October 2024)ICH M13AICH M10 Bioanalytical Method Validation and Study Sample Analysis(November 2022)ICH M10FDA Guidance for Industry:Statistical Approaches to Establishing Bioequivalence(December 2022)FDA BE Statistical GuidanceProduct Specific Guid

6、ance(PSG)2407 PSGs as of 3/8/202661%PSGs with in vivo PK BE Study design recommendationswww.fda.gov5Study ObjectivesStudy Design TypeStudy PopulationDosing ConditionsWashout PeriodBlood Sampling ScheduleComponents of A PK BE Study ProtocolBioanalytical MethodPharmacokinetic AnalysisStatistical Analy