EMA/CMDh: Update Q&A Document for Nitrosamines

The current version of the EMA/CMDh nitrosamine Q&A document "Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products", dated October 2023, contains Annex 1 and three further appendices (Appendix 1-3). These documents are published on the EMA website and can be viewed under "Questions and Answers". The appendices have the following titles

  • Appendix 1 Acceptable intakes (AIs) established for N-nitrosamines 
  • Appendix 2 Carcinogenic Potency Categorisation Approach for N-nitrosamines 
  • Appendix 3 Enhanced Ames Test Conditions for N-nitrosamines

Appendix 1 was compiled by the "Non-clincal Working Party (NcWP)" and the information provided there for the Acceptable Intakes (AIs) is based on the "Carcinogenic Potency Categorisation Approach (CPCA)". This appendix was updated in December 2023. Five substances were newly included and are marked in red and clearly recognisable in the list of Acceptable Intakes (AIs). These include

  • N-nitroso-cinacalcet 
  • N-nitroso-desmethyl-citalopram 
  • N-nitroso-desmethyl-nintedanib 
  • N-nitroso-imatinib 
  • N-nitroso-quetiapine HEEP Impurity

Appendices 2 and 3 continue to exist in their October 2023 version and can be viewed on the EMA website, as can Appendix 1 and the Q&A document for nitrosamines.

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