A Fresenius Kabi cancer drug plant in India savaged by the FDA in the past for hiding serious drug testing issues has been branded with a new warning letter.
The letter to the oncology API plant in Kalyani, Nadia, West Bengal, was issued earlier this month and posted by the FDA this week. While only two observations are outlined in the letter, the FDA said the repeat violations suggest a failure in the company’s production oversight.
“In a previous warning letter (WL 320-13-20), FDA cited similar CGMP deviations. You proposed specific remediation for these deviations in your response,” the letter reads. “These repeated failures demonstrate that your facility’s oversight and control over the manufacture of drugs is inadequate.”
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The warning stems from an inspection last May in which investigators found that employees had halted and invalidated HPLC analyses nearly 250 times when they believed the tests were going to end with out-of-spec results.
Fresenius managers acknowledged that analysts “abort HPLC analyses if they 'expect to invalidate' them later for an assignable cause.” The FDA said it documented 248 such cases. But the FDA said that obtaining an unexpected result does not constitute an “assignable cause” and is not a valid reason to interrupt an analysis.
The agency ordered the plant to do a retrospective review of all invalidated out-of-spec results, both those stopped during analysis as well as in finished tests for products on the U.S. market. It suggested that the company hire a consultant that can help it get its processes in order.
In 2013, the FDA first found big problems at the plant in India. It discovered that plant employees had lied about having blended APIs that failed quality tests into batches that passed in an effort to hit specifications. The company also confessed that during previous inspections, high-pressure liquid chromatography equipment and computers were removed from the plant so investigators wouldn't learn that the plant had been manipulating data to get passing levels. The 2013 letter said Fresenius "repeatedly delayed, denied, limited or refused to provide information to the FDA investigators."
The new problems with the FDA come at a very inopportune time for the drugmaker, which is making massive investments in its manufacturing capabilities in the U.S. to gain a bigger piece of the generic and sterile injectables market there. It has also bought a portfolio of biosimilars, including copies of injected cancer drugs, that it hopes the FDA will approve.
In April, it committed $4.75 billion to buy U.S.-based generics maker Akorn. It will also spend more than $100 million and add 445 jobs at the syringe and drugmaking site in Wilson, North Carolina, that it acquired in 2016 from Becton Dickinson. That project comes on top of the $250 million the drugmaker is investing in a sterile injectables manufacturing site in Melrose Park, Illinois, near its U.S. headquarters in Lake Zurich, Illinois.