A U.S. inspector raised concerns with the Chinese manufacturer of a widely used heart drug more than a year before it was recalled for containing a probable cancer-causing chemical.
A Food and Drug Administration inspection in May 2017 found that the company, Zhejiang Huahai Pharmaceutical Co. Ltd., ignored quality testing that showed unnamed drugs didn’t meet U.S. standards, according to an agency report posted online on Thursday. The company didn’t look into the failures and instead passing results were recorded, according to the report. The blood-pressure medicine, called valsartan, was recalled last month.
Zhejiang Huahai didn’t immediately respond to requests for comment.
“As soon as the FDA was alerted to problems, we initiated an investigation and coordinated with the manufacturers to take swift action to recall all of the affected products,” FDA Commissioner Scott Gottlieb said in an email statement.
The FDA didn’t respond to requests seeking information on when it was alerted to the problems.
The FDA on Thursday also added valsartan made by India-based Hetero Labs Ltd. to the recall. The chemical in the Hetero valsartan exceeds acceptable levels, though is generally lower than levels found in the active ingredient made by Zhejiang Huahai. The Hetero products are labeled under Camber Pharmaceuticals Inc. An FDA inspection uncovered problems at Hetero in 2016.
Hetero’s manufacturing process is similar to Zhejiang Huahai’s, and the FDA has contacted other valsartan makers to determine if their manufacturing processes are at risk.
The FDA has found issues related to drug manufacturing in China and India that have raised concerns about the safety of those pharmaceuticals. More than 80 percent of the ingredients used to make U.S.-consumed drugs are produced outside of the country, according to the agency. China, along with India, accounts for most of the raw ingredients in drugs consumed in the U.S.
The FDA redacted from the Zhejiang Huahai report the names of the drugs that failed quality testing, but the report indicates that the tests were on active pharmaceutical ingredients. Zhejiang Huahai made active ingredients for the drug valsartan, which treats heart failure and high blood pressure and is sold by Teva Pharmaceutical Industries Ltd. and Prinston Pharmaceutical Inc. Those companies recalled the products last month.
The valsartan that was recalled contained a chemical called NDMA, which the U.S. Environmental Protection Agency considers a probable human carcinogen. Based on manufacturing records, NDMA may have been in the impure valsartan for as long as four years.
During impurity testing, Zhejiang Huahai ignored indications of potential problems but they weren’t investigated, the FDA inspector found last year, the report said.
FDA inspectors comb through computer files at drug manufacturing companies to examine the integrity of their testing processes. They also inspect equipment used to make the drugs. The report posted on Thursday found Zhejiang Huahai machines in disrepair.
The inspection covered Zhejiang Huahai’s Chuannan factory in Linhai. Danish authorities have confirmed valsartan’s active ingredient was made in the Linhai factory in the town of Duqiao where the 2017 FDA inspection covers.
The company also has a factory in Xunqiao that the FDA inspected in November 2016. The FDA found workers didn’t follow all procedures meant to prevent contamination and hadn’t established proper controls to ensure drugs met U.S. standards for strength, quality and purity.
It’s unclear if the valsartan active ingredient was also made at the Xunqiao plant. Pharmaceutical companies aren’t required under U.S. law to reveal which drugs they make at which factories. They also can protect as a trade secret where they obtain active ingredient so Americans don’t typically know where their drug ingredients are made unless a major recall necessitates the companies reveal the information.
After each inspection, the FDA told Zhejiang Huahai it needed to voluntarily make corrections to its manufacturing practices.