ANDA 中的常见质量重大缺陷-Yuan.pdf

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1、Common Quality Major Deficiencies in ANDAsGeneric Drugs Forum(GDF)2025Fang Yuan,PhDSenior Pharmaceutical ScientistOffice of Product Quality Assessment I|OPQ|CDER|U.S.FDAApril 10,20252www.fda.govEveryone deserves confidence in their next dose of medicine.Pharmaceutical qualityassures the availability

2、,safety,and efficacy of every dose3Learning Objectives Discuss quality major deficiencies issued in the first cycle major Complete Response Letters(CRLs)in Fiscal Year(FY)2023.Provide recommendations to minimize quality major deficiencies and improve ANDA submission quality.www.fda.gov4www.fda.govOv

3、erview Non-quality disciplines(29%)Bioequivalence:18%Pharmacology/Toxicology:6%Others:5%284 first cycle major CRLs issued in FY2023429 major deficiencies identified Over 70%are quality relatedTop pharmaceutical quality disciplines with major deficiencies:Manufacturing(90%facility&5%process)Drug Prod

4、uct(DP)Drug Substance(DS)5www.fda.govDrug Product Related Major DeficienciesTox-E/L:missing safety assessment of extractables/leachables(E/L)or inadequate assessment of E/LUnqualified impurities:missing toxicological studies to qualify unqualified impurities in drug productDS sameness:insufficient d

5、ata to demonstrate drug substance(DS)sameness esp.for complex active ingredientCQA:critical quality attribute(CQA)not identified or controlled Due to consult:inadequacy(ies)identified through consult for safety assessment,device design,immunogenicity risk,etc.DS sameness,19%Unqualified impurity,20%T

6、ox-E/L,20%CQA,14%Due to consult,7%Miscellaneous,20%6www.fda.govMiscellaneous(each less than 5%):e.g.,-unacceptable analytical method for quality control-unacceptable packaging system to assure adequate product performance due to inadequate dosing accuracy or potential safety risk-insufficient long-t