D2S12-1-Liang-v1.2-FINAL.pdf

1、FDA Nitrosamine Updates and Issues Observed Yuanling Liang,Ph.D.Sr.ChemistDPQA III/OPQA I/OPQCDER|US FDASBIA-Generic Drugs Forum April 23,2026www.fda.gov2DisclaimerThis presentation reflects the views of the speaker which do not necessarily reflect FDA,HHS or other government opinion/policywww.fda.g

2、ov3Objectives Recommended AI limits Implementation Timeline&Progress Updates Emerging Issues Common Issues Observedwww.fda.gov4Why the Nitrosamine Webpage MattersThis webpage is the central regulatory communication tool Updated frequently as new scientific data become available,such as,new AI limits

3、,emerging issues.Immediately implementable Reflects latest science(AI limits,emerging issues)FDA recommendations:Check before and during development Review before submission Reassess when changes occurwww.fda.gov5Webpage contains three tables for the recommended AI limits.Table 1 Theoretical AI limi

4、ts,calculated based on predicted carcinogenic potency categorization(CPCA)Table 2 Compound-specific or Surrogate-Based AI limitsTable 3 Interim AI limits for marketed medical necessity products(serves as temporary regulatory discretion to prevent drug shortage)Key Points:Inclusion in a table confirm

5、ation in your product.AI limits are safety thresholds,not observed levels.Require risk assessment report/Progress Update Recommended AI Limits The Three Tables www.fda.gov6Critical Clarifications on AI Limits Hypothetical,based on molecular structure Not all-inclusive list Can be moved to Table 2 wh

6、en sufficient toxicology data are availableTable 1(CPCA)Use Table 2 AI limits when nitrosamines are moved from Table 1.Table 2 Temporary measures to prevent drug shortage Include estimated duration NOT permanent solution NOT appropriate as specification limits CANNOT be used to justify specification