Second Impurity Found in Recalled Valsartan Drug Products
A second unexpected impurity was shown in 3 lots of Torrent Pharmaceuticals’ recalled drug products during an ongoing FDA investigation.
A second unexpected impurity was shown in 3 lots of Torrent Pharmaceuticals’ recalled drug products during an ongoing FDA investigation. The additional impurity was found in products included in the company’s August 23 recall of drug products containing the active pharmaceutical ingredient (API) valsartan.
This second impurity, N-Nitrosodiethylamine (NDEA), is a known animal and suspected human carcinogen. Previously, various valsartan-containing drug products were recalled due to the discovery of N-nitrosodimethylamine (NDMA), an impurity classified as a probable human carcinogen. The presence of NDMA is thought to be related to changes in the way the active substance was manufactured.
Valsartan is used to treat high blood pressure and heart failure. The impurity NDMA was found in valsartan manufactured by Zhejiang Huahai Pharmaceuticals (ZHP) in China, and utilized in the production of some drug products in the United States, including those recalled by Torrent.
According to the FDA, its testing discovered NDEA in some of ZHP’s valsartan API. The additional impurity also was found in Torrent’s valsartan 160mg (lot BV47D001) and 320mg (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 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. 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,” said FDA Commissioner Scott Gottlieb, MD, in a prepared statement. “As we expand our investigational efforts, we’ll continue to make sure the public has the most up-to-date information. 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. Like NDMA, NDEA is 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.
FDA provides update on its ongoing investigation into valsartan products; and reports on the finding of an additional impurity identified in one firm’s already recalled products [news release]. Silver Spring, MD; September 13, 2018: FDA website. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm620499.htm. Accessed September 13, 2018.