On Aug. 9, FDA expanded its list of valsartan products currently under recall to include other items that contain the active ingredient, which may be tainted with a carcinogenic impurity, manufactured by Hetero Labs Limited in India.
Certain valsartan products contain N-nitrosodimethylamine (NDMA), which is a known carcinogenic impurity.
The FDA noted not all of Camber’s valsartan products that are distributed in the U.S. are being recalled. Test results from Hetero Labs Limited showed the amount of NDMA found in its valsartan active pharmaceutical ingredient exceeds levels deemed acceptable in the U.S., though the amount of NDMA discovered is lower than the amount originally discovered in the tainted products manufactured by Zhejiang Huahai Pharmaceuticals in China.
In a warning letter to Hetero Labs Limited, the FDA noted its investigators observed specific violations including:
- Failure to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed.
- Failure to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.
- Failure to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow such written procedures.
“FDA is working with drug manufacturers to ensure future valsartan active pharmaceutical ingredients are not at risk of NDMA formation,” the FDA noted in an Aug. 2 update. “The agency reminds manufacturers to thoroughly evaluate their API manufacturing processes, and changes to those processes, to detect any unsafe impurities. If a manufacturer detects new or higher levels of impurity, they should take action to prevent changes to the product’s safety profile.”
The FDA first issued a recall of valsartan in last month. Currently, 22 other countries have also issued recall alerts for the drug.