Why the FDA Is Worried About Chinese Drugs in Your Medicine CabinetBloomberg News
Inspections find deleted data, altered quality test records
Chinese companies supply ingredients to top brand drugmakers
When FDA inspectors showed up at a Chinese company that supplies key ingredients to two of the U.S.’s biggest drug companies, a curious thing happened.
After lunch, they walked into a quality control lab on the second floor, where they saw a worker pull what looked like a memory stick from a computer and put it in the pocket of his lab coat. The inspectors asked to see what he’d taken.
And then the man turned and ran.
The U.S. Food and Drug Administration inspectors at Zhejiang Hisun Pharmaceutical Co. never found out what the worker took from the computer, but they found plenty of other things, according to agency documents describing problems at the company, obtained through a Freedom of Information Act request by Bloomberg. There was evidence that quality control staff deleted records of tests that might show a drug was impure. Audit trails disappeared. A paper shredder was kept close by machines that recorded quality data.
The U.S. and the rest of the world are more dependent than ever on China for medicine. Along with India, the country is one of the top two producers of base ingredients for drugs in the world, according to the Institute of Medicine, and the FDA has made inspections there a priority to keep patients safe. It’s found plenty -- the agency has barred 38 plants in China from exporting some or all of their products to the U.S. for manufacturing violations. And 34 facilities are banned from exporting a blood thinning ingredient, after a past scandal, according to the FDA’s import alert list.
Among those Chinese manufacturers, Hisun is one of the largest and makes key components of everything from cholesterol to cancer medicines. Its U.S. customers include companies such as Hospira Inc., now owned by Pfizer Inc., and Merck & Co., which take raw ingredients and turn them into pills and vials for pharmacies and hospitals. At least 15 of Hisun’s products were banned from U.S. import in September.
Hisun said it’s working to fix problems at the plant, and confirmed the broad outlines of the report while declining to discuss each specific violation. The company said it retested the samples in question and said they met standards.
“Hisun is maintaining further communication with the FDA, and actively pushing forward rectifications,” the company said in an e-mailed statement. The company said the man fled over a misunderstanding caused by a language barrier, and that he took an electronic key used for one of the lab machines, not a data storage device.
Hisun isn’t alone in its violations of FDA rules. During an August inspection of another drug ingredient manufacturer, Zhejiang Hisoar Pharmaceutical Co., FDA officials found that quality records had been deleted and test records been altered, with failing results sometimes going unreported, according to records obtained through another Freedom of Information Act request by Bloomberg.
Like Hisun, Hisoar makes ingredients for some of the world’s biggest brand-name drugmakers, including Pfizer and Novartis AG. A 2012 stock exchange filing shows that Hisoar has a 20-year agreement to supply antibiotic products to Pfizer Asia Manufacturing Pte Ltd., a subsidiary of the New York-based drugmaker.
Hisoar declined to comment. China’s drug regulatory body, China FDA, said it didn’t have an immediate comment on the violations or its relationship with the U.S. agency. The FDA declined to comment beyond the inspection documents on Hisun or Hisoar.
Pfizer and Novartis both said they’re aware of the inspection at Hisoar, and were taking action to make sure products were up to quality standards, though didn’t provide specifics. Pfizer said it makes sure products meet standards before reaching the market, and that Hisoar’s problems hadn’t affected the quality of Pfizer’s own products. Pfizer also said it was aware of the inspection at Hisun, and there was no known impact on the quality of its drugs.
Merck can’t discuss supplier relationships, said Pam Eisele, a spokeswoman. The FDA declined to comment on Hisun’s customers or other details.
A fundamental part of the FDA’s inspections in China is checking what’s known as data integrity. It’s a manufacturing standard -- companies make a batch of drug ingredients, test it, record the result, and then preserve that record. Yet the agency’s handful of inspectors in China have found numerous, repeated violations -- many of them deleted records of failed tests that could make it seem like manufacturers are better at making ingredients than they actually are.
While the FDA publicly says that local regulators are cooperating and want to improve standards, China has also being more assertive in recent years, U.S. government reports show. After the Chinese government delayed visas to let FDA staff into the country, the FDA shut down two of its three offices in China. While the visas are now approved, the U.S. agency has just one local staff member in Guangzhou, and none at a former office in Shanghai, according to a U.S. Government Accountability Office report released in January. Even in Beijing, the FDA still has only two permanent drug inspectors as of September.
The “FDA is always looking for ways to be more efficient with its resources and create the necessary synergies among FDA staff at foreign posts, and decided to consolidate its offices in China within the U.S. Embassy in Beijing,” said Jeff Ventura, an FDA spokesman.
There are serious risks to patients when drugs aren’t up to standard. In 2008, a blood thinner called heparin was made with contaminated Chinese ingredients, and 246 deaths in the U.S. were linked to the medicine, according to the FDA. Regulators never found at what point the ingredients in the drug, made by Baxter International Inc., were contaminated. At the time, Baxter said it was alarmed that the contamination appeared to have been deliberate, though said it didn’t have proof of how it happened.
The FDA closed its initial criminal investigation into the tainted heparin after it became difficult to obtain evidence in China, though it has since re-opened a related inquiry, according to the House Energy and Commerce Committee. The FDA declined to comment on an open investigation.
From 2012 to 2014, Hisun received at least 11 complaints from customers about their ingredients, including that weren’t up to purity standards, according to the inspection documents. Hisun hadn’t kept any records of the tests that supposedly confirmed that the ingredients were okay, the FDA found during the March inspection.
There were a litany of related violations. “It appears that your laboratory practice is to delete failing and/or undesirable results and repeat analyses until passing and/or acceptable results are achieved,” the FDA said in the Hisun inspection report.
In one example, the FDA found Hisun employees had turned off software that creates an audit trail while conducting impurity tests in 2014. The initial results were deleted and the FDA said Hisun never investigated why. Instead, the tests were repeated two days later and those results were sent to the FDA.
There’s also the issue that Hisun knew about problems -- senior quality management employees told the FDA that the company had been aware of the “potential for data manipulation” since July 2014, according to the agency.
Hisoar also had data violations. According to the FDA, when they’d test a drug ingredient and find it wasn’t of high enough quality, they sometimes wouldn’t report it, according to inspection documents. In some cases, they’d test it again until it passed, turning failure into success.
— With assistance by Hui Li, and Anna Edney