CMDh/EMA: Appendix 1 for Nitrosamines Revised

In the current version of July 2024, 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" contains three appendices (Appendix 1-3). These documents are available on the EMA website under "Questions and answers".

Appendix 1 was compiled by the "Non-clincal Working Party (NcWP)" and the information provided for the Acceptable Intakes (AIs) is based on the "Carcinogenic Potency Categorization Approach (CPCA)". In February 2025, new substances were added to Appendix 1; the substances are listed in tabular form. The new entries are marked in red in the list of Acceptable Intakes (AIs) and are easily identifiable. The following substances are newly listed:

• 2-(N-nitrosomethylamino)-N-[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]acetamide
• N-nitroso-dalbavancin 
• N-nitroso-dasatinib 
• N-deshydroxyethyl-N-nitroso dasatinib
• N-nitroso-desmethyl-cabergoline
• N-nitroso-desmethyl-lercanidipine
• N-nitroso-desmethyl-lercanidipine impurity D
• N-nitroso-N-desmethyl-mianserin 
• N-nitroso-norfloxacin 
• N-nitroso-sarcosine 
• N-nitroso-vancomycin

Appendices 2 and 3 as well as Appendix 1 and the Q&A document for nitrosamines can be viewed on the EMA website.