EMA Provides Update on Nitrosamine Impurities in APIs

The European Medicines Agency (EMA) has provided an update on the work of European Union (EU) and national authorities to prevent and manage the presence of nitrosamine impurities in EU medicines.

The issue of nitrosamine impurities in certain active pharmaceutical ingredients (APIs) first emerged in 2018 with “sartan” APIs, such in 2018, when the EMA and the US Food and Drug Administration (FDA) initiated investigations of nitrosamine impurities in certain “sartan”-containing APIs, used in anti-hypertensive and cardiovascular drugs, such as valsartan candesartan, irbesartan, losartan, and olmesartan. They later broadened those investigations into prescription and over-the-counter forms of ranitidine, a H2 (histamine-2) blocker used to decrease the amount of acid created by the stomach as well as into metformin, a diabetes drug.

Nitrosamines are classified as probable human carcinogens based on animal studies. They are present in some foods and water supplies and are not expected to cause harm when ingested at very low levels, according to the EMA. In the few medicines where they have been found, the risk to patients is expected to be low.

The EMA reports that a review by the EMA’s Committee for Medicinal Products for Human Use (CHMP) is currently considering evidence on how a nitrosamine, N-nitrosodimethylamine (NDMA), came to be present in some batches of ranitidine. In addition, the EMA and national authorities are assessing the impact of recent tests which found NDMA in some EU batches of metformin medicines.

The EMA says that further results from tests on metformin in the EU are being awaited. As metformin is considered a critical medicine, the EMA and national authorities are cooperating closely to avoid possible shortages.

The EMA says that an ongoing procedure aimed at providing guidance to companies on how to deal with nitrosamines in medicines is currently gathering evidence and considering opinions from experts in the EU. As a result of this procedure, which began in September 2019, measures to evaluate and mitigate the risk of nitrosamines are being implemented across the EU.

Authorities in the EU are also conducting an exercise to determine what lessons can be learnt from the presence of nitrosamines in sartans, which came to light in mid-2018. The EMA says its “lesson learnt group” is currently finalizing recommendations to prevent and better manage the presence of impurities in the future.

The EMA says it will continue working closely with national authorities, The European Directorate for the Quality of Medicines and HealthCare (EDQM) and international partners and will take all necessary measures to protect the quality of medicines in the EU.

Source: European Medicines Agency

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