Europe – EMA addresses risk evaluation, mitigation for nitrosamines

An updated question-and-answer document from the European Medicines Agency (EMA) provides guidance on handling nitrosamine impurity testing for marketing authorization holders.

Marketing authorization holders (MAHs) are to perform a risk evaluation to ascertain whether chemically synthesized active pharmaceutical ingredients (APIs) are at risk for containing nitrosamines by 31 March 2021. Products containing biological APIs should undergo this first step in risk evaluation by 1 July 2021.

After completing a review launched in September 2019, EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that some biological medicines might also be at risk for containing nitrosamine impurities, so the current call for review has been extended to include biological medicinal products. Biologics particularly at risk include those containing chemically synthesized fragments, those where nitrosating reagents are added, and those packaged in nitrocellulose blister packs.

The initial evaluations are followed by a second step of confirmatory testing when risk is involved. Step 2 testing should be completed and reported to EMA by 26 September 2022 for chemical APIs and by 1 July 2023 for biological APIs…