EMA/CMDh: Appendix 1 for Nitrosamines Updated Again

Recommendation

14-16 May 2024
Vienna, Austria

Analytical Instrument Qualification
Practical Approaches for USP General Chapter <1058> Compliance in the QC Laboratory

The nitrosamine Q&A document "Questions and answers for marketing authorization 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 appendices (Appendix 1-3) in its current version of October 2023. These documents are published on the EMA website and can be viewed under "Questions and answers".

Appendix 1 was prepared by the "Non-clinical Working Party (NcWP)". The information provided there regarding the Acceptable Intakes (AIs) is based on the "Carcinogenic Potency Categorization Approach (CPCA)". This appendix was updated again in February 2024. Fifteen substances were added which are highlighted in red and clearly recognizable in the list of Acceptable Intakes (AIs).

These include:

• 2,2,5-trimethyl-3-nitroso-1,3-oxazolidine
• N-nitroso-apixaban Impurity B
• N-nitroso-clozapine
• N-nitroso-clozapine EP Impurity C
• N-nitroso-desmethyl-tamoxifen
• N-Nitrosodiisopropanolamine
• N-nitroso-flecainide
• N-nitroso-folic acid
• N-nitroso-masitinib
• N-nitroso-meglumine
• N-nitroso-meropenem
• N-nitroso-ritalinic acid
• N-nitroso-silodosin
• N-nitroso terazosin Impurity C
• N-nitroso terazosin Impurity N

Appendices 2 and 3 are still available in their October 2023 version and, like Appendix 1 and the Q&A document for nitrosamines, can be viewed on the EMA website.