Nitrosamines are chemical compounds classified as probable human carcinogens on the basis of animal studies.
EU regulators 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'.
that could cause cancer in humans.
Hence 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.
EMA and CMDh have published documents on their websites, (EMA/189634/2019 and CMDh/404/2019), “Information on nitrosamines for marketing authorisation holders” which request marketing authorisation holders (MAH) to follow an investigation process described for synthesised APIs (other than sartans).
Step 1 - Risk evaluation
Step 2 - Confirmatory testing
Step 3 - Revision to the CEP
The risk evaluation for all CEPs was (should) concluded by 26th March 2020. The deadline for Step 2:confirmatory testing remains unchanged: 26 September 2022.
The European medicines regulatory network has agreed to extend the deadline for submissions related to Step 3: variation to the marketing authorisation until 1 October 2023.
This extension is intended to allow companies time to perform a thorough investigation and establish any required risk-mitigating actions.
The Nitrosamine Implementation Oversight Group (NIOG) oversees the harmonised implementation of the CHMP's Article 5(3) opinion on nitrosamines.
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