FDA warning letter tells Cadila to resolve problems with warfarin production

The FDA has found something it likes at a Cadila Healthcare plant. A week after the agency posted a warning letter for Cadila's formulation plant in Moraiya and its Zyfine API plant, the Indian drugmaker says it has gotten an OK for its Baddi plant.

The drugmaker received an Establishment Inspection Report (EIR) this week that it reported in a filing to the Bombay Stock Exchange, the Economic Times reports. An EIR is issued when the FDA has closed out its inspection of a facility. The company reported it that will allow it to seek approvals for other products from the plant in Himachal Pradesh.

That is not the case for Cadila's formulation and API plants in Gujarat, where the FDA had serious concerns about Cadila's production of warfarin products following inspections in 2014. According to the FDA warning letter, at least 5 batches fell short of expectations, but the drugmaker never uncovered the root cause so that it could be fixed.

The drugmaker at one point in 2014 stopped production of the blood thinning med to investigate why products kept failing specification tests. After about two months of looking into the problems, Cadila indicated it believed they were resolved and resumed production. But the FDA says that it learned later, the problems with tablets failing tests also resumed and Cadila still didn't know the reason.

"These persistent failures indicate that your manufacturing process is not in a state of control. Nevertheless, at this time, drugs from this facility are being released to the market," the warning letter says.

The FDA ordered Cadila to send it a list of all warfarin batches with out-of-specification and out-of-trend results, whether they were shipped to the U.S. or other markets, along with test results from a contract laboratory. It gave the company a list of ways it should be determining the cause of the problem then said: "Finally, provide your justification for continued production and explain how you have ensured that your marketed product is safe."

On top of the warfarin production problems, the FDA said there were 9 instances in three years in which there were consumer complaints that pharmacists found the wrong product mixed into some bottles of meds. The FDA was not only unhappy that the drugmaker didn't look into the specific complaints but had failed to see if it was a problem affecting other products.

And there was a long list of concerns directed at the API plant, including the fact there were no official records about potential water contamination even though an FDA inspector found an "unofficial notebook" saying there had been an investigation into "Pseudomonas present" in the water for a product.

Cadila has indicated that this time around, it will make sure it gets its investigations right. When Cadila acknowledged the warning letter in an earlier BSE filing, it said it takes quality seriously and will do what is necessary to meet FDA expectations. "We are committed to resolve all the issues and revamp our quality systems and processes as the top most priority," it said in the filing.

- here's the warning letter