D2S16-Lu-v1.2-FINAL.pdf

1、Bioanalysis of Endogenous Drugs Using Surrogate Matrix Approach in Abbreviated New Drug ApplicationsYang Lu,Ph.D.Division of Bioequivalence IIIOffice of BioequivalenceOffice of Generic DrugsCDER,US FDASBIA Generic Drug Forum April 23,2026www.fda.gov2DisclaimerThis presentation reflects the views of

2、the presenter and should not be construed to represent FDAs views or policieswww.fda.gov3Learning objectivesDescribe the bioanalytical challenges of endogenous drugs in ANDAsSummarize different approaches recommended in the ICH M10 guidance for endogenous drug bioanalysisExplain the surrogate matrix

3、 approachEvaluate analytical data acceptability in case studies using the surrogate matrix approach,implementing ICH M10 criteria and FDA regulatory assessmentwww.fda.gov4Endogenous DrugsEndogenous molecules play important physiological and pharmacological roles Examples:sex hormones,thyroid hormone

4、s,fatty acid,elemental iron,vitamins,etc.Endogenous molecules as the active pharmaceutical ingredients(APIs)in ANDAsPost-dose endogenous drug concentrations are the fundamental data for pharmacokinetic(PK)assessment to demonstrate bioequivalencewww.fda.gov5Endogenous Drug BioanalysisBioanalysis of e

5、ndogenous drug concentrations is challenging!“Interference”of the endogenous levelYu,C.et al.,Bioanalysis,2024 Feb;16(3):171-184www.fda.gov6ICH M10 RecommendationsSection 7.1-Methods for analytes that are also endogenous moleculesRecommended approaches Surrogate matrix Surrogate analyte Background s

6、ubtraction Standard additionICH M10,Nov 2022www.fda.gov7Surrogate matrix Benefits of the surrogate matrix approach Analyte-free Robustness Promising sensitivity Interference-free authentic matrix(same matrix type as BE study samples)is acceptablewww.fda.gov8Case study 1 method sensitivityEndogenous