In September 2023, WHO Prequalification Team - Medicines (PQT/MED) recognized new approaches to determine acceptable intakes (AIs) for nitrosamine impurities in medicines developed by medicines regulatory authorities:
https://extranet.who.int/prequal/news/update-n-nitrosamine-impurities
The use of the less-than-lifetime (LTL) concept described in ICH M7 (R2) for short treatment durations has now been recognized by several medicine regulatory authorities as applicable to nitrosamine impurities based on new evidence.
A suggested reference is the European Medicines Agency (EMA) Questions and answers document on nitrosamine impurities where recent information on the LTL framework for nitrosamines and related clarifications can be found:
Reference to similar guidance issued by other regulatory agencies may also be made.
For eligible products used for short treatment durations the LTL approach may be used now to propose adjusted AI limits for nitrosamine impurities in Active Pharmaceutical Ingredients Master Files (APIMFs) and Finished Pharmaceutical Products (FPPs) for new applications including those already under assessment and for accepted APIMFs and prequalified products.
Clinical uses, maximum daily doses and treatment durations applied by PQT/MED are based on the therapeutic treatments referred to in the various FPP Invitations for Expression of Interest (EOIs):
https://extranet.who.int/prequal/medicines/fpps-apis-eligible-prequalification-eois
For further clarification, please contact Mr Wondiyfraw Worku (FPPs) at zelekew@who.int and Dr Antony Fake (APIs) at fakea@who.int.