Regulatory Focus™ > News Articles > In Second Warning Letter to Wockhardt, FDA Alleges Rampant and Familiar Quality Problems

In Second Warning Letter to Wockhardt, FDA Alleges Rampant and Familiar Quality Problems

Posted 03 December 2013 | By Alexander Gaffney, RAC

Indian pharmaceutical manufacturers have been under heightened scrutiny from the US Food and Drug Administration (FDA) in 2013, with several major companies experiencing disastrous inspections that revealed a host of troubling allegations. Now another company, Wockhardt, is the recipient of a Warning Letter from the US agency alleging that several of its facilities appeared to be faking data and otherwise lacked controls to prevent data manipulations.


Wockhardt had last been issued a Warning Letter from FDA in July 2013, when inspectors said the company's employees had intentionally tried to deceive them and interfere with their investigation.

"Your firm repeatedly delayed, denied, limited an inspection or refused to permit the FDA inspection," FDA stated at the outset of the letter. For example, FDA said after one of its investigators identified vials of an unknown substance that were either unlabeled or partially labeled, an employee - a QC analyst - then "immediately began dumping the contents of the vials into the drainage sink," effectively destroying the evidence.

In another alleged incident, a quality assurance employee of Wockhardt was asked to bring "torn raw records in the waste area" that had been observed to the investigator. However, when the employee brought documents over as requested, none of them appeared to be what the FDA officer had observed. That investigator then repeatedly pressed the employee as to whether there were any other records, and he was reportedly told, "No, this is all of the records." The investigator then revisited the waste area, where he found all the original data records in a different holding bag, presumably moved by the employee. Those records, FDA said, included raw data testing worksheets, Master Batch Records, requirement calibration records, and stability protocol records.

Several other Indian companies have been sent Warning Letters as well. Fresenius, Hospira, Promed, and Posh Chemicals have all been sent letters this year, and a lengthy investigation of Ranbaxy concluded in 2013 with a $500 million fine for the company-the largest criminal fine ever levied by FDA.

Common Deficiencies

Although the letters have highlighted different deficiencies, one thing has remained consistent: The nature of the alleged violations. Regulatory Focus has read thousands of Warning Letters over the years; We can think of only a small number that reflect violations as concerning as those reflecting in the aforementioned letters.

Ranbaxy was ultimately convicted of falsifying data used to support generic drug applications. Fresenius and Wockhardt were accused poor data practices, absent management and interfering with inspectors. Posh was outright accused by FDA of falsifying data. Promed was found to have inadequate aseptic manufacturing practices.

Wockhardt Warning Letter

And FDA's newest letter to Wockhardt regarding two of its facilities is no exception in this regard, mirroring many deficiencies found by FDA in its first Warning Letter in July 2013 and those found at other Indian facilities.

The facilities, located in Waluj and Chikalthana, both in the state of Maharasthtra in western India, were found to be significantly deficient in their operations.

FDA said that at both locations, it found evidence of the company conducting initial "trial" testing of products before final testing. The testing is ostensibly intended to ensure that product meet specifications for purity, potency and quality. However, FDA said it found evidence that the final results were being manipulated.

"We are concerned because our investigator noticed that the "trial" injection data related to batch [Redacted] rendered an out-of-specification (OOS) result for the [Redacted] and [Redacted] assays," FDA wrote. "Therefore, it appears that the batch [Redacted] did not pass the "trial" analysis but met specifications when the "official" sample was tested shortly thereafter."

This "trial" injection practice was used across both facilities and multiple drug products, FDA found.

Dubious Data

Equally disturbing, FDA found evidence that the company had deleted all of its internal "trial" injection data after FDA found deficiencies at its other manufacturing facility in July 2013, implying that the company was looking to cover up other potential deficiencies.

FDA said it was concerned that there were insufficient controls to guard against data manipulation of unfavorable results-a concern that wasn't just hypothetical, regulators added. "It appears that QC analysts attempted to mask the practice of performing sample "trial" injections by labeling them as standards rather than by the actual batch numbers or other identifying information," FDA observed, referencing the company's response to an FDA Form 483.

Together with the earlier Warning Letter, FDA said it was "particularly concerned about [Wockhardt's] inability to implement a robust and sustainable quality system." FDA said the "trial" injection issue was made known to the company after its previous inspection at its other facility, but that the issue went unaddressed and continued up until its most recent inspection.

Elsewhere, FDA said it also found that there were no unique log-ins for quality staff, allowing quality analysts to "access and manipulate" data without any accountability.

Both sites are now subject to an import alert until they are re-inspected and found to be compliant, FDA said.

Warning Letter to Wockhardt


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