亚硝胺生物等效性方法-Kaur.pdf

1、Bioequivalence Approaches for Nitrosamine Impacted ANDA Applications:Case StudiesParamjeet Kaur,Ph.D.Division of Bioequivalence II,Office of BioequivalenceOffice of Generic Drugs,CDER/FDA SBIA Generic Drug Forum April 10,20252DisclaimerThe opinions and information in this presentation are those of t

2、his presenter and does not necessarily represent views and/or policies of the U.S.Food and Drug Administration3Topics for DiscussionBackgroundBioequivalence(BE)Approaches for Drug Products Impacted by Nitrosamine ImpuritiesCase StudiesSummary4BackgroundSince 2018,several commonly prescribed drug pro

3、ducts have been found to contain unacceptable levels of nitrosamines,with some classified as probable human carcinogens.Nitrosamine issues impact a wide range of drug products and dosage forms,including both New Drug Applications(NDAs)and Abbreviated New Drug Applications(ANDAs)(the majority).The in

4、dustry may need to adopt various strategies to mitigate nitrosamine impurities,including but not limited to changes to active pharmaceutical ingredient(API),drug product manufacturing process,excipient/formulation.5BE Approaches for Drug Products Impacted by Nitrosamine Impurities Guidance for Indus

5、try:Control of Nitrosamine Impurities in Human Drugs(Revision 2;Sept 2024)includes a recommendation for an alternative BE approach that could be utilized for reformulated products of nitrosamine impacted applications.The recommendation is based on FDA research results Addition of certain antioxidant

6、s or pH modifiers to formulations may significantly inhibit nitrosamine formation1 Addition of small amounts of four antioxidants(ascorbic acid,-tocopherol,propyl gallate,or cysteine)do not affect permeability of BCS Class III model drugs2 Addition of small amounts of antioxidants do not affect inte