CMDh/EMA: New Update to Appendix 1 on 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' contains three appendices (Appendices 1-3). These documents are published on the EMA website and can be viewed under the heading 'Questions and answers'.

Appendix 1 was compiled by the Non-clinical Working Party (NcWP), and the data provided therein regarding Acceptable Intakes (AIs) are based on the Carcinogenic Potency Categorisation Approach (CPCA). In March 2026, new substances were added to Appendix 1, which consists of a tabular list of substances, and some data was updated. These are marked in red in the list of Acceptable Intakes (AIs) and are clearly identifiable.

The new substances included:

• 6-nitro-N-nitrosoadrenaline
• N,N'-dimethylethylenedinitrosamine
• N-nitroso-adrenaline
• N-nitroso-brensocatib
• N-nitroso-dabigatran etexilate amide
• N-nitroso-desbutyldronedarone
• N-nitroso-desmethyl-cidoxepin
• N-nitroso-desmethyl-diltiazem
• N-nitroso-desmethyl-ulipristal acetate
• N-nitroso-diazepam Impurity D
• N-nitroso-methylethylamine
• N-nitroso-N-descyclopropanecarbaldehyde olaparib
• N-nitroso-remibrutinib

The updated entries include:

• 3-(dimethylamino)propyl 2-[benzyl(nitroso)amino]benzoate
• 3-((ethyl(nitroso)amino)methyl) benzenesulfonate
• N-nitroso-folic acid
• N-nitroso-labetalol
• N-nitroso-meglumine
• N-nitroso-paroxetine
• N-nitroso-vancomycin

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