Chinese Plant Linked To Valsartan Recalls Gets Warning Letter Over Manufacturing Problems

Federal drug regulators say inspections of a Chinese generic drug manufacturing plant linked to a series of recent valsartan recalls have revealed a number of problems and violations. 

The FDA issued a warning letter to Zhejiang Huahai Pharmaceutical Co. Ltd (ZHP) late last month, according to a press release issued Tuesday. Investigators say they found problems with impurity control, and evidence of cross contamination from one manufacturing line to another in a facility linked to batches of valsartan recalled because they contained the cancer-causing impurity N-nitrosodimethylamine (NDMA).

The inspections took place at the China facility from July 23 to August 3, 2018, according to the letter. The inspectors found that the facility failed to adequately respond to, and resolve, quality-related complaints.

In one specific instance, FDA investigators determined the plant received a complaint in June by a customer who received batches of the active pharmaceutical ingredient (API) valsartan that were contaminated with NDMA. The company’s investigation determined that only one valsartan manufacturing process had been affected by NDMA contamination. However, the FDA found multiple batches contaminated with NDMA after being manufactured through an entirely different process, leading inspectors to determine that ZHP’s investigation had been inadequate.

The first valsartan problems surfaced in July, when European regulators announced that batches of the active ingredient supplied by Zhejiang Huahai Pharmaceuticals in China, tested positive for NDMA.

The FDA followed with its own recall announcement the following week, indicating that the agency had launched an investigation to determine the scope of the contamination and the potential risk to consumers. Since that time, the recall has been expanded several times, impacting a variety of manufacturers of the generic drug.

In September, the FDA stopped all imports of drug ingredients and medicines made by ZHP.

ZHP officials argued that they were not the only manufacturer linked to the presence of NDMA in valsartan. However, the FDA letter notes that their levels were the highest detected.

“In your case, FDA analyses of samples identified amounts of NDMA in valsartan API manufactured at your firm that were significantly higher than the NDMA levels in valsartan API manufactured by other firms,” the letter states. “FDA has grave concerns about the potential presence of mutagenic impurities in all intermediates and API manufactured at your facility, both because of the data indicating the presence of impurities in API manufactured by multiple processes, and because of the significant inadequacies in your investigation.”

The FDA’s warning letter indicates ZHP is still on Import Alert, which means that the agency is continuing to refuse to allow the company’s drug products into the United States until adequate corrections are made.

The agency is also continuing to test other valsartan drugs, as well as other similar hypertension drugs, like irbesartan, which has also suffered recalls due to similar cancer-causing impurities. The FDA is asking patients who use the drugs to regularly check its updated list of recalled valsartan drugs, recalled irbesartan drugs, and its list of valsartan drugs that have not been recalled.

As more individuals discover that they may have received contaminated pills, a growing number of valsartan recall lawsuits are being filed, including claims that individuals may have avoided a cancer diagnosis if NDMA has not been in the generic hypertension drugs.