D2S13-2-Crowley-v1.2-FINAL.pdf

1、Extractable/Leachable Safety Assessment in Generic Drug ProductsGeneric Drug Forum 2026Vince Crowley,PhDSenior PharmacologistDivision of Pharmacology/Toxicology Review(DPTR)Office of Safety and Clinical Evaluation(OSCE)Office of Generic Drugs(OGD)CDER|FDAApril 23,20262DisclaimerThis presentation ref

2、lects the views of the author and should not be interpreted to represent FDAs view or policies.www.fda.gov3Outlinewww.fda.govExtractable/Leachable Safety Review in Generic DrugsKey Factors for Safety ReviewCommon Pitfalls4E/L Safety Review in Generics Extractable and Leachable(E/L)studies identify c

3、ompounds that may migrate from manufacturing equipment or container closure system(CCS)Extractables exaggerated laboratory conditions Leachables drug product storage conditions The Quality review team confirms the adequacy of study design and analytical methods,OGD Pharm/Tox evaluates E/Ls observed

4、above safety thresholds Pharm/Tox assesses mutagenicity,general toxicity,and local toxicity of E/Ls based on context of use5Key Factors for Safety ReviewRoute of AdministrationDuration of Treatment 10 yearsDuration of Treatment 10 yearsMost Routes11.5 g/day5 g/dayTopical Ophthalmic products2Reportin

5、g Threshold:1 ppmIdentification Threshold:10 ppmQualification Threshold:20 ppm1.Drug products administered via sensitive routes(e.g.,intrathecal)may require a lower Safety Concern Threshold(SCT)(e.g.,0.15 g/day).A Controlled Correspondence(CC)can be submitted to OGD to obtain guidance on appropriate

6、 safety thresholds for a specific drug product.2.FDA Guidance for Industry Quality Considerations for Topical Ophthalmic Drug Products(December 2023);https:/www.fda.gov/media/172937/download;ppm(parts per million)is used due to the risk of local toxicity to the eye.6Key Factors for Safety ReviewIden