The US Food and Drug Administration (FDA) has issued a stern warning to the Indian pharmaceutical manufacturer Cadila regarding various deficiencies at its drug production facility in Ahmedabad, including serious problems with the systems needed to ensure testing data isn't falsified.
The letter to Cadila is the 13th sent by FDA to an Indian pharmaceutical company regarding so-called "data integrity" issues since May 2013.
For a complete listing, please see Regulatory Focus' Data Integrity Tracker.
Regulators see good data as a linchpin of good manufacturing practices (GMPs), and for good reason. If regulators are unable to trust the data indicating that testing was done properly, at the correct time and by the correct people, they are unable to determine with any certainty whether products made at a site are safe, effective or manufactured according to the proper standards.
In several cases, FDA has found that companies without adequate protections against "unauthorized manipulation" of data have re-entered drug testing data to make it seem as though non-compliant products actually passed their quality tests. This has been done by either outright falsification of data, by re-testing products repeatedly until they pass (and then entering the data as though that was the first and only test), or by keeping "unofficial" records and recording only those products that pass as having been tested.
At its worst, insufficient data protection can make a bad drug product or active pharmaceutical ingredient look alright to regulators, which may be why FDA has been cracking down so hard on companies found to have engaged in data falsification. Many companies found to have engaged in the process are immediately added to FDA's import alert list, which prevents the companies from importing their products into the US.
New Warning for Cadila
Now Cadila has found itself in the same crosshairs as the other dozen Indian pharmaceutical manufacturers before it. In a Warning Letter posted on FDA's website on 11 November 2014, FDA accuses the company of failing to have in place "proper controls … to prevent the unauthorized manipulation of [its] electronic raw data."
Agency inspectors found that an "audit trail" feature on one gas chromatography instrument wasn't turned on until October 2013 despite the feature being in place since 2009. In another example, FDA said it found that electronic raw data generated by gas chromatography units were connected to stand-alone computers capable of deleting data.
In addition, Cadila "failed to have a back-up system for the data generated" by several pieces of manufacturing equipment.
Cadila has reportedly now moved to a centralized data collection system, and is in the process of implementing a more permanent Laboratory Information Management System (LIMS), according to FDA's letter.
The letter is Cadila's second in less than four years. Another facility in Ahmedabad—it's not clear from FDA's Warning Letter if it is the same one warned in its 2014 letter— was sent a warning in June 2011 after FDA inspectors found other serious GMP deficiencies, including inadequate environmental monitoring.
At least one problem found in 2011 was again found during FDA's most recent inspection of the facility, the agency said. For example, FDA alleged the company failed to properly investigate several customer complaints—a problem observed in 2011.
FDA also noted that "numerous stability samples have not been tested at the required intervals"—an observation apparently also made during an inspection in 2012. Many samples were backlogged, causing samples to be "overdue for testing." FDA inspectors said they were "concerned that [Cadila's] quality unit was not aware of this backlog situation."
Cadila was given 15 days to respond to the letter, and FDA indicated that it might withhold approval for any new drugs using materials manufactured at the Admedabad facility, and might also put the company's products on import alert. To date, FDA does not appear to have subjected the company to an import alert.
FDA Warning Letter to Cadila
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