FDA Finds More Impurities in Recalled High Blood Pressure Drug Valsartan
The FDA has found an additional impurity in its ongoing investigation of several recently recalled drug products containing the active pharmaceutical ingredient (API) valsartan, used to treat high blood pressure and heart failure. The investigation began in June 2018 after a manufacturer detected a probable carcinogen, N-nitrosodimethylamine (NDMA), in the API, which followed with other companies recalling products.
The FDA’s latest testing of products shows an additional unexpected impurity in three lots of recalled valsartan drug products from Torrent Pharmaceuticals’, Novo Nordisk’s Ahmedabad, India-headquartered manufacturing partner. This second impurity, N-Nitrosodiethylamine (NDEA) is a known animal and suspected human carcinogen. These Torrent products were included in the company’s recall on August 23, 2018.
The FDA and the European Medicines Agency have also learned that Zhejiang Huahai Pharmaceuticals (ZHP), a Linhai, China-based pharmaceutical company that earlier detected NDMA in the API, found NDEA in several batches of its valsartan API. The FDA immediately began retesting all valsartan API and products, including both recalled products and those currently marketed in the US, for NDEA. Based on FDA testing to date, the agency discovered NDEA in some of ZHP’s valsartan API. This impurity was also found in Torrent’s valsartan 160-mg (lot BV47D001) and 320-mg (lots BV48D001 and BV48D002) tablets, which were made using API from ZHP and were part of the earlier recall. The FDA’s testing shows that not all products made using ZHP’s valsartan API contain the NDEA impurity.
“As we continue to investigate the root cause of the impurities found in products that contain valsartan, our scientists are testing these products to better understand these impurities and to ensure they’re not present in other products,” said FDA Commissioner Scott Gottlieb, MD, in a September 13, 2018 agency statement. “We’re also taking steps to make sure we’re providing stringent oversight of manufacturing processes to reduce the likelihood that impurities could be introduced into other products…We’ll also continue to work with global regulatory agencies to learn as much as we can about how these impurities came about and how they may affect patients’ health around the globe.”
The FDA is continuing to test all products that contain valsartan for NDEA and related impurities. If the agency finds NDEA in products that have not been recalled, the FDA said it will work with companies to ensure all affected products are removed from the market. The agency is also evaluating the risks NDEA in these products poses to patients. The FDA says it expects to complete this risk analysis in the coming days and will continue to provide updates to the public as new information becomes available.
Like NDMA, NDEA is also formed from a specific sequence of manufacturing steps and chemical reactions. In addition to the FDA’s testing, the agency will post a preliminary method for detecting NDEA. Manufacturers and global regulators can use this method to screen other products for the potential presence of this impurity.
Additionally, the agency says it will update the list of products included in the recall and the list of products not included in the recall as products are tested for NDEA and as more information becomes available.