EMA Issues Implementation Plan for Reducing Nitrosamine Impurities

By Miranda Greenberg -

November 5, 2020

The European Medicines Agency (EMA) has issued a detailed plan to implement recommendations for reducing the risk of medicines that contain nitrosamine impurities.

Certain nitrosamines are classified as probable human carcinogens, and nitrosamine impurities have been the subject of investigations by the EMA and the US Food and Drug Administration in several active pharmaceutical ingredients (APIs) dating back to 2018. These products include “sartan”-containing APIs, used in anti-hypertensive and cardiovascular drugs, such as valsartan candesartan, irbesartan, losartan, and olmesartan. These investigations were later expanded to include ranitidine, a H2 (histamine-2) blocker used to decrease the amount of acid created by the stomach, and most recently into metformin extended-release products, a diabetes drug.

The plan identifies short-, medium-, and long-term recommendations based on recommendations from lessons learned from the presence of N-nitrosamine impurities in sartan medicines.

The EMA also provided templates for marketing authorization holders (MAHs) to perform risk-assessment testing. The plan issued last month (October 2020) correlates with an earlier report from the EMA on how to avoid the presence of nitrosamine impurities in human medicines.

In June (June 2020), the EMA finalized a review to provide guidance to MAHs on how to avoid the presence of nitrosamine in human medicines. EMA's Committee for Medicinal Products for Human Use also asked all marketing authorization holders to review all chemical and biological human medicines for the possible presence of nitrosamines and test products at risk. In August, (August 2020), the EMA issued a questions-and-answers (Q&A) document on risk-assessment and risk-mitigation measures required of MAHs with respect to nitrosamines impurities.

Source: European Medicines Agency