EMA Initiates Review of Nitrosamine Impurities in Ranitidine; To Develop Guidance for APIs

As part of its investigation of nitrosamine impurities in certain active pharmaceutical ingredients (APIs), the European Medicines Agency’s (EMA) Executive Director Guido Rasi has asked the EMA’s Committee for Medicinal Products for Human Use (CHMP) to provide guidance for avoiding the presence of nitrosamine impurities in human medicines containing chemically synthesized active substances.

Nitrosamines are classified as probable human carcinogens. In 2018, nitrosamines were found in a number of blood-pressure medicines known as “sartans,” which lead to a recall of several products and a review by the EMA, which set strict new manufacturing requirements for these medicines.

“It is of paramount importance that we learn from our experience with sartans and take a proactive approach for other classes of medicines,” said Rasi in a September 13, 2019 EMA statement.

The EMA began investigations into nitrosamine impurities in sartan APIs in 2018. Since then, a nitrosamine impurity has been detected in a few batches of pioglitazone, an API in a diabetes medication, from one company and in batches of ranitidine, an API used as an H2 (histamine-2) blocker used in over-the-counter and prescription drugs to decrease the amount of acid created by the stomach. An EU-wide review of ranitidine has been initiated. Also, the US Food and Drug Administration recently reported that it had detected a nitrosamine impurity in ranitidine (see related story).

Drawing on work already carried out by the Coordination Group for Mutual Recognition and Decentralized Procedures, the EMA said that the CHMP will now provide guidance on avoiding the presence of nitrosamine impurities to marketing authorization holders, which they should consider alongside their knowledge of the manufacturing processes of their products.

In addition, the CHMP says it will consider whether to provide guidance for medicines other than those containing chemically synthesized APIs. The EMA says it will continue to work closely with national authorities, European Directorate for the Quality of Medicines and international partners to ensure that effective measures are taken to prevent these impurities from being present in medicines.

The CHMP will also evaluate all available scientific knowledge on the presence of nitrosamines in medicines and advise regulatory authorities on actions to take if companies find nitrosamines in their medicines. In addition, the committee will consider whether to provide guidance for medicines other than those containing chemically synthesized active substances.

Source: European Medicines Agency

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