D2S15-Dandamudi-v1.2-FINAL.pdf

1、ICH M13A High-risk vs Non-high-risk Case Studies-BE ImplicationsSuman Dandamudi,Ph.D.Lead PharmacologistDivision of Bioequivalence III/Office of BioequivalenceOffice of Generic Drugs|CDER|US FDASBIA Generic Drugs Forum April 23,2026www.fda.gov2Disclaimer:This presentation reflects the views of the p

2、resenter and should not be construed to represent FDAs views or policies.www.fda.gov3Learning ObjectivesProvide an overview of ICH M13A guidanceExplain the FDAs framework for risk-based categorization of solid oral immediate release(IR)productsDescribe bioequivalence(BE)study recommendations for hig

3、h-risk vs non-high-risk productsHighlight the cases studies showing impact of M13A guidance from a bioequivalence perspectivewww.fda.gov4M13A Bioequivalence Guidance for Immediate-Release Solid Oral Dosage FormsM13A guidance harmonizes global approaches for conducting BE studies on immediate-release

4、 solid oral dosage formsDrug products are classified into two categories based on their potential for bio-inequivalence:High-risk Products:Drug substance characteristics in combination with the complexity of formulation design or manufacturing process lead to an increased likelihood that gastrointes

5、tinal(GI)conditions(fasted and fed state)will differentially impact in vivo performance Non-high-risk ProductsRisk-based approach to determine BE study conditionswww.fda.gov5FDAs Framework-Risk Classification Determination Biopharmaceutic properties Biopharmaceutics Classification System(BCS)class o

6、f drug,drug solubility across physiological pH range Complexity of the formulation design or manufacturing process of the products to improve solubility and/or pk performance Solid dispersions,microemulsions,co-processed drug substances,nanotechnologies,lipid based formulations Critical excipients t