CHMP: Test all metformin for nitrosamines before release

Regulatory NewsRegulatory News | 19 October 2020 |  By 

Medicines containing the diabetes medication metformin must be tested for the presence of nitrosamines before being released into the European market, said a committee of the European Medicines Agency (EMA) following its scheduled September meeting.
“As of October 2020, EMA and the national competent authorities are asking marketing authorization holders for metformin-containing medicines to test their medicines before releasing them onto the market,” said EMA’s Committee on Human Medicinal Products (CHMP) in an update to its post-authorization nitrosamine impurity testing procedures. (RELATED: EMA addresses risk evaluation, mitigation for nitrosamines, Regulatory Focus 06 August 2020)
An Article 5(3) review is underway, and the testing requirement is a “precautionary step” as CHMP – and regulators worldwide – grapple with how to detect and manage the presence of nitrosamine impurities. The substance occurs naturally in minute amounts, but elevated levels may be carcinogenic.
The detection of nitrosamine at elevated levels in pharmaceutical products is complicated both because the amounts being measured are extremely small – mere nanograms of nitrosamines reach the threshold of impurity in medicines – and because some testing methods themselves may result in nitrosamines being formed, skewing results.
Nitrosamines have been found at elevated levels in the antacid ranitidine, in certain anti-hypertensive medications and tuberculosis drugs, and in extended release metformin.
The US Food and Drug Administration has announced voluntary recalls of extended release metformin marketed by several different firms, and in September 2020 put guidance immediately into effect that details steps for prevention and detection of nitrosamine impurities. (RELATED: N-Nitrosamine impurities: FDA issues detection, prevention guidance, Regulatory Focus 01 September 2020)


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