Health Canada has identified a second impurity, N‑nitrosodiethylamine (NDEA) in valsartan manufactured by Zhejiang Huahai Pharmaceuticals in China. All drugs containing valsartan manufactured from that source have already been recalled in Canada after the first impurity, N-nitrosodimethylamine (NDMA), was identified earlier this summer. Both, NDEA and NDMA are classified as probable human carcinogens, which means that long-term exposure could cause cancer.
Besides Health Canada, also the EMA and the US FDA have released further reviews on valsartan medicines. Together with other international regulatory partners they are investigating the root cause of the issue. The EMA’s risk assessment considers the life-time risk of cancer to be low. It is estimated to be in order of 1 in 5,000 for an adult patient who had taken an affected valsartan medicine at the highest dose (320 mg) every day from July 2012 to July 2018. The low risk estimate is to some extent supported by a Danish study which tracked patients who had taken medicines containing valsartan from Zhejiang Huahai over the past 6 years. However, the authors note that patients were followed up for a relatively short period (4.6 years on average).
Data on levels of NDEA are currently very limited, and both, Health Canada and EMA will provide further information on whether its presence impacts the risk assessment once more information becomes available. Meanwhile EU authorities have carried out inspections of the manufacturing sites of the involved companies (Zhejiang Huahai and Zhejiang Tianyu) in China and will consider the findings.
Medicines containing valsartan from the two manufacturers are no longer distributed in the EU or have been recalled. Both companies are not currently authorised to produce valsartan for medicines in the EU.
The US FDA has also updated its investigation results and also reports on the finding of the additional impurity NDEA identified in products of Torrent Pharmaceuticals Ltd. Torrent’s valsartan was already part of an earlier recall of August 2018. The API used again originated from Zhejiang Huahai Pharmaceuticals. Currently the FDA is continuing to test all products that contain valsartan for NDEA and related impurities.
Health Canada: Recalls and Alerts
EMA: Press Release
FDA: Press Announcement