Nitrosamines, or more correctly N-Nitrosamines, refer to any molecule containing the nitroso functional group. These
molecules are of concern because nitrosamine impurities are probable human carcinogens. Although they are also
present in some foods and drinking water supplies, their presence in medicines is nonetheless considered unacceptable. The European Medicines Agency (EMA) has assessed the risk of nitrosamine formation or presence during the
manufacture of human medicines and has provided guidance to marketing authorization holders to avoid the presence
of nitrosamine impurities.
Recently, there is an update to guidance for MAH on root causes and risk factors for nitrosamine contamination (Q&A
4) and on policy for confirmatory testing (Q&A 8) and dossier requirements (Q&A 15) to allow testing of intermediates, raw materials or API under certain circumstances. EMA finalized a review under Article 5(3) of Regulation (EC) No
726/2004 in June 2020 to provide guidance to marketing authorization holders on how to avoid the presence of nitrosamine impurities in human medicines.
Agency has posted their responses to the industry’s questions in FDA website. While the document provides information regarding some of FDA’s current thinking on the nitrosamine impurities, there are several topics which need clarification. One of the major questions is related to nitrosamine drug substance related impurities (NDSRIs). The NDSRIs
have their origin in the drug substance itself and thus, dicult to control without understanding the source of nitrosating agent in the route of synthesis of the drug substance and the formulation of the finished product. The other question that has been troubling industry is the acceptable levels of NDSRIs in their drug products. Agency, in the May 4th,
2021, meeting has expressed that “read across” may be acceptable in setting limits of NDSRIs. However, with nitrosamine related data being far and few in literature, this may be challenging.
The third edition of Nitrosamine Impurities forum scheduled on 8th- 9th June 2022 online, aims to discuss on the
recent developments related to nitrosamine impurities, the challenges facing by the pharmaceutical industry and work
towards possible solutions that may lead to a world with lower levels of nitrosamines.