CMDh/EMA: Appendix 1 for Nitrosamines updated again

The 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" of the EMA/CMDh contains three annexes (Appendix 1-3) in the current version of January 2024. These documents are published on the EMA website and can be viewed under "Questions and answers".

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)". In July 2024, new substances were added to Appendix 1, which consists of a tabular list of substances, and some existing entries in the list were updated. These are marked in red in the list of Acceptable Intakes (AIs) and are clearly recognisable. They include

  • 1-diphenylmethyl-4-nitrosopiperazine
  • 3-(dimethylamino)propyl 2-[benzyl(nitroso)amino]benzoate
  • Nitroso-STG-19
  • N-Nitroso-bilastine impurity 2
  • N-nitroso-caspofungin
  • N-Nitroso-desformyl-riociguat
  • N-nitroso-desmethyl-clarithromycin
  • N-nitroso-desmethyl-citalopram
  • N-nitroso-desmethyl-tramadol
  • N-nitroso-desvaleryl-valsartan
  • N-nitroso-diisopropylamine
  • N-nitroso-ethylisopropylamine
  • N-nitroso-N-desmethyl-diphenhydramine
  • N-nitroso-N-methyl-4-aminobutyric acid
  • N-nitroso-tigecycline
  • N-nitroso-trandolapril

Please visit the EMA website to take a look at the Annexes 2 and 3 as well as Appendix 1 and the Q&A document for nitrosamines.

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