Nitrosamines are chemical compounds classified as probable human carcinogens on the basis of animal studies. There is a very low risk that nitrosamine impurities at the levels found in medicines could cause cancer in humans.
Regulators in the European Union (EU) first became aware of nitrosamines in medicines in mid-2018 when nitrosamine impurities, including N-nitrosodimethylamine (NDMA), were detected in blood pressure medicines known as 'sartans'.
Scientific experts in the EU carried out a review of these impurities in EU medicines under Article 5(3) of Regulation (EC) No 726/2004.
The CHMP's Article 5(3) opinion provides guidance for managing, detecting, and preventing impurities like nitrosamines in human medicines.
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EMA finalised a review under Article 5(3) of Regulation (EC) No 726/2004 in June 2020 to provide guidance to marketing authorisation holders on how to avoid the presence of nitrosamine impurities in human medicines.
The CHMP asked marketing authorisation holders to review all chemical and biological human medicines for the possible presence of nitrosamines and test products at risk by following the guidance on nitrosamines impurities.
Companies are required to have appropriate control strategies to prevent or limit the presence of these impurities and, where necessary, to improve their manufacturing processes.
The CHMP's assessment report is available below.
An implementation plan agreed in February 2021 sets out how the European medicines regulatory network, together with the European Directorate for the Quality of Medicines & HealthCare (EDQM) on implementing the outcome of the CHMP's review.
This includes specific measures that the network takes if nitrosamines are detected in a medicine.
EMA and national competent authorities continue to monitor the presence of nitrosamine impurities in medicines, in cooperation with regulators from outside the European Union (EU). They also work with marketing authorisation holders to find rapid solutions to address any adverse findings.
The Nitrosamine Implementation Oversight Group (NIOG) oversees the harmonised implementation of the CHMP's Article 5(3) opinion on nitrosamines.
The European medicines regulatory network set up this oversight group in February 2021, in line with its implementation plan.
The group reports on progress to EMA's Management Board and the Heads of Medicines Agencies (HMA).
It contains representatives from the CHMP, CMDh, EMA working parties, EDQM and EMA staff.
It also enables pharmaceutical industry stakeholders to discuss regulatory and scientific developments on nitrosamines with EMA and the European medicines regulatory network.
For details of meetings involving pharmaceutical industry stakeholders and supporting documents, see:
More information on the group's mandate, activities and composition is available in the document below: