EMA recalls heart medicine valsartan made by Chinese firm over potential cancer-causing residue

Several heart drugs containing valsartan are being recalled in Europe and Asia after a Chinese active ingredient manufacturer found residues of a substance in its supplies that could cause cancer.

China’s Zhejiang Huahai Pharmaceutical voluntarily informed the European Medicines Agency (EMA) that it had identified N-nitrosodimethylamine (NDMA), a chemical that might lead to cancer, in its valsartan provided to the European market, the agency said in a release last Thursday. As a result, medicines containing valsartan made by Huahai are being recalled across Europe, while the EMA carries out a thorough review to determine the impact.

Valsartan, a drug first developed by Novartis to treat high blood pressure and heart failure, has already gone off patent and is used in many medicines made by several drugmakers. Novartis itself markets valsartan under the brand name Diovan, along with other valsartan-containing drugs like Exforge and Entresto. Teva’s Actavis, Stada and Dexcel Pharma are among others selling the drug.

In a statement shared with FiercePharma, Novartis said it is recalling Sandoz's valsartan and valsartan HCT distributed in 23 countries due to the impurity, while its Novartis branded products and those made for the U.S. are not affected.

“The presence of NDMA was unexpected and is thought to be related to changes in the way the active substance was manufactured,” said the EMA. According to Huahai’s disclosure made to the Shanghai Stock Exchange, the new manufacturing system had previously obtained approvals from related countries, and the amount of NDMA detected is “extremely small.”

Novartis, in its statement, also said “the amount of NDMA found in valsartan API is neither considered to represent a significantly increased risk to patients taking Sandoz valsartan or Sandoz valsartan HCT film coated tablets nor having an effect on the efficacy of the product.”

NDMA is currently classified in Group 2A as a probable carcinogen by the World Health Organization’s International Agency for Research on Cancer, meaning there’s limited evidence of the agent’s cancer-leading effect in humans.

Drug agencies in Japan, Taiwan and Hong Kong have also issued recall, and as of Monday, Huahai said it has not heard from the U.S. FDA. In a statement (Chinese) published on Monday on its official social media account, Novartis’ China branch said none of the valsartan-containing products it sells in mainland China are affected because its APIs come from outside of the country.

Huahai said no regulatory agency has currently placed restrictions on NDMA, but in the interest of public health, it has suspended manufacturing and supply of valsartan, sealed its unshipped batches and informed customers and regulators. In the meantime, it is currently engaging with regulators including the U.S. FDA to push for the establishment of an industry standard on NDMA.

Located in Zhejiang province, Huahai was among the first Chinese companies to get drugs approved in the U.S. It has in many cases passed FDA GMP inspections and has formed supply agreements with some of the largest pharma companies around the world, including Novartis and Merck. During an online investor conference on Monday, the company said its other products are not affected due to having a different manufacturing process.

As a major valsartan API maker, Huahai sold CNY 328 million ($50 million) worth of the ingredient in 2017. The company saw its stock price in Shanghai slip more than 20% on the news.