This alert relates to a recent change to the step 3 deadline for the European Medicines Agency’s (EMA’s) call for review for nitrosamine impurities. The call to review requires marketing authorization holders (MAHs) to review their manufacturing processes in order to identify and, if necessary, mitigate the risk of nitrosamine impurities being present in their medicines and report back to authorities. Following a recent update to EMA guidance, the deadline for completion of step 3 of the call to review for nitrosamine impurities for products containing chemically synthesized active pharmaceutical ingredients (APIs) is October 1, 2023.
The call to review for nitrosamine impurities consists of three steps. Under step 1, MAHs are required to perform a risk evaluation to determine whether APIs and/or finished product could be at risk of the presence of nitrosamines. If a risk is identified under step 1, step 2 requires that MAHs proceed with confirmatory testing in order to confirm or refute the presence of nitrosamines. Finally, under step 3, if the presence of nitrosamines is confirmed, MAHs should implement effective risk mitigation measures through submission of a variation. This three-step review process parallels the calls to review issued by other regulators, including the U.S. Food and Drug Administration (FDA) and Health Canada.
EMA has issued deadlines for completion of all three steps. For human medicines containing chemically synthesized APIs, EMA instructed that the step 1 risk evaluation should be concluded and reported by March 31, 2021. For step 2, EMA has requested that confirmatory testing be completed by September 26, 2022. Previously, EMA imposed this same deadline for completion of step 3 for products containing chemically synthesized APIs. On July 29, 2022, however, EMA issued a revision of its guidance document. EMA, 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 (July 29, 2022). Per this updated guidance, the deadline for completion of step 3 for products containing chemically synthesized APIs is now October 1, 2023.
For products containing biological APIs, EMA instructs that step 1 should be completed by July 1, 2021, while steps 2 and 3 are both expected to be finalized by July 1, 2023.
If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drug, and Devices practice.
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