According to the European Medicines Agency’s (EMA) press release on 26 September 2019, EMA’s human medicines committee (CHMP) is requesting that all marketing authorisation holders (MAHs) for human medicines containing chemically synthesised active substances review their medicines for the possible presence of nitrosamines and test all products at risk. If nitrosamines are detected, MAHs must inform authorities immediately so that appropriate regulatory actions can be taken. MAHs are responsible for ensuring that every batch of their finished product is of satisfactory quality, including the active substances and other ingredients used to make them.

Nitrosamines are classified as probable human carcinogens, and prolonged exposure above a certain level may increase cancer risk. Nitrosamines can be formed, for example, during the manufacture of sartans (angiotensin II receptor blockers) or because of contaminated equipment and reagents. The main nitrosamines detected in EMA’s study of sartans were N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). For these impurities, temporary limits have been set in accordance with the current international guideline of ICH (M7(R1)). Medicines containing impurities above these limits or medicines containing both nitrosamines at any level are not allowed in the EU.

What is expected of you as MAH of human medicinal products and when?

EMA gives guidance to companies on how to avoid nitrosamines and to evaluate the possibility of nitrosamines being present in human medicines.

You should use the dedicated templates provided by EMA and CMDh for submitting the risk evaluation (step 1) and confirmatory testing (step 2) responses to the authorities.

EMA also provides guidance to companies manufacturing sartans (angiotensin II receptor blockers).

This summary was compiled by Pharmaceutical Chemical Expert Sari Virtanen at Medfiles Ltd.

If you have any questions or need support for the risk evaluation of nitrosamines in human medicines, Medfiles is happy to help you.
Please don’t hesitate to contact us for more information.


Minna Haapalahti
Minna Haapalahti
Director, Regulatory Affairs and Safety
Tel. +358 20 744 6821
Mob. +358 40 585 7596

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Heta Karvinen
Senior Pharmaceutical Chemical Expert
Tel. +358 20 744 1504
Mob. +358 40 189 9565


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