EDQM New strategy for N-nitrosamine impurities in Ph. Eur. Monographs

European Pharmacopoeia Commission (EPC) approved the new strategy for N-nitrosamine impurities in individual monographs in November 2023. As per the new strategy a specification for N-nitrosamine impurity will be included in a monograph only when it is a process-related impurity, i.e. generated during synthesis of the substance, or a degradation impurity arising from its storage. The Production section referring to N-nitrosamines in individual monographs on active substances will be deleted in existing monographs and avoided in new monographs.

EPC decided not to address the following types of potential N-nitrosamine contamination in individual monographs –

• impurities resulting from manufacturing practices during synthesis of the API (recovered or recycled materials, cross-contamination);
• impurities potentially generated during the manufacture or storage of the medicinal product;
• potential risk of future transformation into a nitrosamine (e.g. secondary amines).

Accordingly, the individual monographs of sartans – (Valsartan, Irbesartan, Candesartan cilexetil, Olmesartan medoxomil and Losartan potassium) will be revised. The revised monographs will be published in European Pharmacopoeia (Ph. Eur.) Supplement 11.6 and implemented as from 1 January 2025.

The Production section covering N-Nitrosamines is being deleted from the individual monographs as it is already covered by general requirement for N-nitrosamines in revised general monograph (2034). While the individual monographs no longer include a Production section discussing Nitrosamine impurities, the need to regulate these impurities remains in the general monograph requirements

New strategy for N-nitrosamine impurities in Ph. Eur. Monographs (EDQM)