On 7 July 2023, the EMA published a revised version of the “Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products”.
This update includes new scientific approaches for categorisation of N-Nitrosamines and for establishing Acceptable Intakes (AIs), as well as a separate Appendix listing those N-nitrosamines for which AIs have been established by the EMA Non-clinical Working Party (NcWP). These approaches have been agreed together with international partners.
The EDQM has always implemented the principles of the EU Article 5(3) referral and the associated Q&As on active substances covered by CEPs, and therefore the new approaches and the newly established AIs will also be implemented for CEPs from now on.
What should CEP holders and applicants do:
- In those cases where N-nitrosamines have been newly categorised, CEP holders may update their risk assessment, control strategy and their CEP application in accordance with the new AIs and submit a request for minor revision to the EDQM. Similarly, for revisions related to nitrosamine impurities that are currently under assessment, CEP holders are encouraged to proactively update their risk assessment and CEP application in accordance with the newly established AIs and to submit the relevant data to the EDQM.
- For new N-nitrosamines and those not listed in the Appendix of the EMA Q&As document, the Carcinogenic Potency Categorization Approach (CPCA) described in the EMA Q&As should be used to determine the potency category and associated AI to be considered in the risk assessment and the related control strategy.
Any questions related to a specific CEP application can be addressed to the EDQM via the usual e-mail box (with reference to the CEP dossier).
European Medicines Agency - Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products