D2S17-Rhieu-v1.2-FINAL.pdf

1、Lyophilization in Pharmaceutical Manufacturing:Deficiencies,Control Strategies,and Regulatory ExpectationsSteve RhieuCDR,US Public Health ServiceOffice of Pharmaceutical Manufacturing AssessmentCDER|US FDAGeneric Drugs Forum 2026 April 23,2026Disclaimer:This presentation reflects the views of the sp

2、eaker and should not be construed to represent FDAs views or policies.www.fda.govwww.fda.gov2Learning Objectives Manufacturing unit operations-lyophilization Common deficiencies in drug applications Common control strategies used Inspectional findingswww.fda.govwww.fda.gov3Poll QuestionWhich of the

3、following is the definition of lyophilization found in the 1993 FDA guide to inspections of lyophilization of parenterals?A.A process of transition where solid ice from a product turns into liquid waterB.A process of transition where liquid water from a product turns into water vapor C.A process in

4、which water is removed from a product after it is frozen and placed under a vacuum,allowing the ice to change directly from solid to vapor without passing through a liquid phaseD.None of the abovewww.fda.govwww.fda.govLyo drugs approved per year*FDA lyo drug approvals by types of applicationsAccount

5、ing for 5%of ca.800 generics reviewed annuallyMost frequent process-related deficiencies result from lyophilization*Trends in lyophilization*LyoHUB annual report 2025*AAPS J.(2020)22,100www.fda.govwww.fda.gov5Manufacturing unit operations Compounding Filtration Aseptic filling Lyophilization(or free

6、ze-drying)Crimping/packagingwww.fda.govwww.fda.gov6Common lyo deficiencies Formulation specific issues Poor lyo cycle development Incorrectly identifying endpoint of drying Cake collapse No data/justification for scale-upwww.fda.govwww.fda.gov7Regulatory expectations Reduce uncer