EMA Extends Valsartan Review to Include Four More Active Substances

Regulatory NewsRegulatory News | 21 September 2018 |  By 

The European Medicines Agency (EMA) announced Friday it has extended its review of two impurities classified as probable human carcinogens from its initial valsartan focus to include medicines containing four other “sartans.”
The move to include candesartan, irbesartan, losartan and olmesartan in the ongoing review was prompted by the detection of “very low levels of N-nitrosodiethylamine (NDEA)” in the losartan products manufactured by Hetero Labs in India, EMA said.
NDEA was the second probable human carcinogen to have been detected by regulatory authorities worldwide, including EMA, the US Food and Drug Administration and Health Canada. The first— N-nitrosodimethylamine (NDMA)—resulted in an international recall of valsartan-containing medicines from several China-based suppliers that EMA initiated in July.
“How these impurities came to be present during the manufacture of sartans is yet to be fully established and is being evaluated in the ongoing review,” EMA added.
FDA, meanwhile, has issued at least three Forms 483s to the first China-based valsartan supplier to have been linked to the drug safety issue—Zhejiang Huahai Pharmaceuticals—based on manufacturing site inspections conducted from 2016 to 2018. 
“Based on the trace amounts of NDEA seen so far in one batch of losartan from Hetero Labs, there is no immediate risk to patient,” the European agency clarified. “Further tests are required to determine the extent of the contamination and whether impurities are present in sartan medicines above levels that can be considered acceptable.”
Last year, FDA issued a warning letter to India-based Hetero Labs over violations of good manufacturing practices. The violations cited relate to investigating process deviations and out-of-specification results, equipment manufacturing conditions and quality unit failures. The agency also issued a Form 483 to a Hetero Labs branch—Hetero Drugs—earlier this year.


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy