Confidence Beyond Compliance

In June 2018, authorities (FDA, EMA, etc.) became aware of the presence of a nitrosamine, N-nitrosodimethylamine (NDMA), in valsartan substance from one active pharmaceutical ingredients (APIs) manufacturer. Subsequently another nitrosamine, N-nitrosodiethylamine (NDEA), was detected and other ‘sartans’ from more API manufacturers were later implicated. NDMA and NDEA are classified as probable human carcinogens and their presence in ‘sartans’ was, at the time, unexpected.

On the 13th September, 2019, the FDA announced that preliminary tests found low levels of NDMA in Ranitidine (original brand name Zantac®). Subsequently to this announcement, Sanofi voluntarily recalled over-the-counter (OTC) ranitidine due to possible NDMA contamination. Moreover, pharmaceutical companies such as Novartis and Apotex announced that they are recalling all their generic ranitidine products sold in the US and other territories too.

Following a review of ‘sartans’ risk, a general advice letter summarises FDA and EMA findings to date and provides recommended actions to be taken to ensure that the drug product, drug substance / API, and raw materials are absent of these impurities or below recommended limit.

The EMA has come up with a notification (EMA/189634/2019, dated 19th September 2019) specifying its expectation on the risk assessment of nitrosamines in the medicinal products. The advice states that all authorised human medicinal products containing chemically synthesised APIs are to be reviewed, including generics and OTC products. However, in view of the large number of authorised products, MAHs should use a risk-based approach and prioritise their evaluations and confirmatory testing. This risk evaluation for all products should be submitted before 26th March, 2020.

If you would like help in understanding and acting on the guidance, please contact us to see how we might be able to support you – contact@pharmalex.com.

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As leading experts in regulatory affairs, PharmaLex have written a detailed whitepaper on the background and recommended steps required to ensure your medicinal products comply with the latest guidance for nitrosamines.

To download our Whitepaper, click here>>

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