ICH M13A 实施对生物等效性评估的影响：因暴露量低而删除数据-Vivian.pdf

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1、Impact of ICH M13A Implementation on Bioequivalence Assessment:Removal of Data due to Low ExposureDiana Vivian,Ph.D.Associate Division DirectorDivision of Bioequivalence II,OGD/OBCDER|US FDASBIA Generic Drugs Forum April 10,2025fda.gov/cdersbiafda.gov/cdersbia2Disclaimer:This presentation reflects t

2、he views of the presenter and should not be construed to represent FDAs views or policies.fda.gov/cdersbiafda.gov/cdersbia3Learning Objectives Provide an overview of the ICHM13A guidance recommendations regarding removal of bioequivalence(BE)study data due to low exposure Highlight case studies show

3、ing how the Office of Bioequivalence(OB)has implemented these recommendations,including how the scientific principles have been applied for non-immediate release(IR)productsfda.gov/cdersbiafda.gov/cdersbia4Per the FDA draft Guidances for Industry:Bioequivalence(BE)Studies with Pharmacokinetic Endpoi

4、nts for Drugs Submitted Under an ANDA(Aug 2021)and Statistical Approaches to Establishing Bioequivalence(Dec 2022),data should not be removed from bioequivalence studies due to identification of statistical outliers.Such data was generally only removed with real time documentation of a protocol devi

5、ation;otherwise,it is not clear if the anomalous data could be due to other factors such as product failure.In limited cases,an exception was made due to data below the limit of quantitation(BLQ)which precluded calculation of a subject periods pharmacokinetic(PK)parameters,i.e.,if test/reference(T/R

6、)ratio could not be calculated for the subject.Previous Practice Regarding Low Exposure Data Removalfda.gov/cdersbiafda.gov/cdersbia5Removal of BE Study Data Due to Low ExposureSection II.B.(Data Analysis for Non-Replicate Study Design)1.a.Generally,data should not be removed from the statistical an