D2S13-1-Xu-v1.2-FINAL.pdf

1、1A RISK-BASED APPROACH TO EXTRACTABLES AND LEACHABLES EVALUATIONSJin Xu,PhDSenior Pharmaceutical Quality Assessor FDA/CDER/OPQ/OPQAII4/23/2026www.fda.gov2DisclaimerThis presentation is not intended to convey formal FDA policy.www.fda.gov3Presentation Outline Introduction Risk assessment Leveraging p

2、rior knowledge Using indirect food additive regulations(21 CFR 174-186)to support oral drugs Post approval supplementswww.fda.gov4Introduction Extractables Chemical entities released from a manufacturing equipment or CCS into an extraction solvent under laboratory conditions.Leachables Chemical enti

3、ties released from a manufacturing equipment,or CCS leached into a drug product during manufacturing and storage.USP/Technical references-PQRI publications FDA Guidance-CCS for packaging human drugs and biologics(1999)www.fda.gov5Risk Assessment Product SpecificMaterials of construction and processi

4、ng aids information fromCCS manufacturersPrior knowledgeRoute of administrationDuration of treatmentMaximum daily exposureFormulation composition and leaching propensityPotential interaction between CCS and drug productStorage conditions and shelf-lifewww.fda.gov6Leveraging Prior Knowledge in Initia

5、l Risk Assessments Prior knowledge with the same or a similar products usingsame CCS may be used to support new applications withproper justification-Same route of administration Same or similar product composition Similar or less leaching propensity Similar or less maximum daily exposurewww.fda.gov

6、7Oral Drug ProductsOral route of administration considered lower riskCompliance with 21 CFR 174-186 and relevant USP standards may besufficient to support use of CCS for oral drugs Applicants should cite specific sections,subsection,and use conditions of the r