缓释制剂简略新药申请中常见的生物等效性缺陷-Kim.pdf

1、Common Bioequivalence Deficiencies in Abbreviated New Drug Applications for Extended-Release Drug Products Juhyun Kim,Ph.D.Division of Bioequivalence III,Office of Bioequivalence,Office of Generic DrugsCDER|US FDA(April 10,2025)Disclaimer:This presentation reflects the views of the author and should

2、 not be construed to represent FDAs views or policies fda.gov/cdersbiafda.gov/cdersbia2OutlineCommon bioequivalence(BE)deficiencies identified for extended-release(ER)drug product First-cycle BE adequacy rate and review time for ER drug product Case study for BE deficiencies on dissolution testing u

3、sing scored tablets Recommendations for avoiding BE deficienciesfda.gov/cdersbiafda.gov/cdersbia3Learning Objectives Summarize common first-cycle BE deficiencies in ANDAs for ER drug products Learn from a case study on BE deficiencies in ER formulations to better understand the common BE deficiencie

4、s impacting 1st cycle approval for ER products Identify strategies to prevent some of these deficienciesfda.gov/cdersbiafda.gov/cdersbia4Common BE Deficiencies for ER Drug Product PK,17%Bioanalysis,35%Dissolution,37%Formulation,11%157 ANDAs1 were submitted until 12/31/2024.224 first cycle deficienci

5、es were identified.1 Evaluated ER Tablet Drug Products:(1)Memantine,(2)Oxymorphone,(3)Tramadol,(4)Metoprolol Succinate,(5)Paliperidone,(6)Glipizide,(7)Oxybutynin Cl,and(8)Quetiapine Fumarate.fda.gov/cdersbiafda.gov/cdersbia5Common BE Deficiencies for ER drug Product(contd)Dissolution(37%)Missing/ina

6、dequate multi-pH media dissolution-9%Missing/inadequate dissolution data for scored tablets 9%Lack of discriminatory ability for the dissolution method 9%Missing/inadequate alcohol dose-dumping data 6%Pharmacokinetics(17%)Subject exclusion without proper justification 4%Missing/inadequate informatio