25 August 2022

Update on EMA’s Question and Answer document for MAH’s regarding nitrosamine impurities

European Medicines Agency (EMA) has published the 11th revision 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 (EMA/409815/2020 Rev.11, 29th of July 2022) and extended the deadline for submission of variations from 26th of September 2022 to 1st October 2023. This gives pharmaceutical companies an extended timeframe of 12 months to take measures to reduce the risk of nitrosamine contamination and to submit the relevant variations to their competent authority. In doing so, the submission of incomplete data of the confirmatory examination should be avoided. The deadline for conducting the confirmatory review, 26th of September 2022 for medicinal products with chemically-synthesised active pharmaceutical ingredients and 1st of July 2023 for those with biological active pharmaceutical ingredients remains unchanged.


Shortly after the publication of the aforementioned, the notification addressed to all CEP holders was published in the EDQM newsroom regarding this extension of the deadline. European Directorate for the Quality of Medicines & HealthCare (EDQM) explicitly points out the obligation of CEP holders to provide their customers with all information related to risk assessments of their products with regard to nitrosamines, so that they in turn can fulfil their obligations as marketing authorisation holders towards the authority. There is also a guidance document of the EDQM CEP holders responsibilities towards their customers (PA/PH/CEP (21) 57) on this information obligation of CEP holders, published in January 2022.

Another update relates to the form for step 2, which has been amended to include a checkbox for confirming that the result of the risk analysis after step 1 is to be changed from “risk” to “no risk”. This option for a subsequent change can be used if relevant information was still missing at the time of submission of the risk assessment and only became available after the deadline for step 1 (31 March 2021 for chemically-synthesised substances and 1 July 2021 for biological substances). A subsequent change vice versa, from “no risk” to “risk”, cannot be made with this form.