Dear Nitrosamine Exchange Community,
I would appreciate any experience or feedback regarding regulatory expectations for nitrosamine risk assessments in Phase I short-term clinical pharmacology studies (e.g., SAD/MAD trials) conducted in healthy volunteers, typically with treatment durations of less than one month.
In particular:
- Have regulators accepted the use of time-adjusted Acceptable Intake (AI) limits based on Less-Than-Lifetime (LTL) corrections as described in ICH M7(R2) for nitrosamines across all CPCA categories?
- Have any concerns been raised regarding the applicability of LTL-adjusted limits for high-potency nitrosamines, particularly those classified within CPCA Categories 1 or 2?
- For early-phase development programs, is a high-level nitrosamine risk assessment generally considered sufficient, given that formulations, synthetic routes, manufacturing processes, and control strategies are often still evolving throughout development?
- Have any agencies requested more extensive assessments or additional supporting data specifically for Phase I studies?
Any insights, examples, or experiences from recent regulatory interactions would be greatly appreciated.
Many thanks in advance.
Best regards,
Diego