FDA warning letter scorches a second Apotex plant in India

Apotex's Bangalore, India, plant

A plant in Bangalore, India, operated by Canadian generic drugmaker Apotex has been accused of manipulating testing data, 10 months after the FDA banned another of its Indian facilities for doing the same thing. The accusation adds to a significant list of infractions that have rained down on the company in the last 5 years from the agency.

The FDA said in the warning letter sent to Apotex last week and posted Tuesday that Apotex has responded 7 times to the FDA observations, most recently in early January, and the FDA found its proposed corrective actions fell short of expectations every time. In the warning letter, the agency ordered Apotex to do a more thorough investigation of all of the deficiencies and then present the agency with a global plan of action that includes whether the company will be contacting customers and recalling suspect products.

In an email, Apotex said Tuesday it "has dedicated significant resources to further reinforce our culture of quality. We have implemented improved training programs and applied new procedures to mitigate the risk of employee error through enhanced quality assurance measures and third-party validators." It went on to contend that customers can be confident that its drugs are safe and effective.

But FDA findings outlined in the warning letter might cast doubt on that contention. Among the infractions, the letter says, inspectors found it was a "common practice" for the plant to do "trial testing" of samples and then delete those that didn't meet specifications and report only those that did. In fact, for one kind of unidentified drug, the FDA said "2,803 of 44,643 injection results were not processed or reported in the official data folder for dissolution analysis." That amounts to more than 6.2% of results. Plant officials said they knew about the practice and allowed it without further investigation, believing the results were not indicative of the norm.

The letter also criticizes the plant for not protecting computer equipment in such a way to as reduce the chance of employees deleting test results. It pointed out that Apotex analysts had created unauthorized "folders" on some of them.

When it came to microbial testing, the FDA said inspectors found plates and samples were often missing from incubators when records indicated they should be there. A follow-up investigation by the company found 290 plates and 36 media tubes under testing were missing. The company said most of those were discovered in the decontamination area for disposal. It blamed a couple of analysts who "panicked" and discarded the samples "in an utterly misguided and ill-conceived attempt to clean up the microbiology lab prior to the start of the FDA inspection." Perhaps, the FDA said, but that doesn't explain why procedures were not being followed in the first place.

Many of the issues were the same kinds of problems the FDA laid out in its June warning letter for the other Apotex plant in Bangalore, a plant that it had added to its import alert list in April. In fact, Apotex has a long history with dealing with FDA observations at plants in Canada and India. Two of its Canadian plants were banned from shipping products to the U.S. from 2009 to 2011. New warning letters were issued to the plants in 2013, when the FDA again found issues. Those warning letters were closed out by the FDA last May but several months ago, Apotex reportedly received a new Form 483 for issues at its plant in Ontario.

- here's the January warning letter
- here's the June warning letter

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