Regulatory Focus™ > News Articles > Warning Letter to Wockhardt Details Extraordinary Failures, Efforts to Deceive FDA Inspectors

Warning Letter to Wockhardt Details Extraordinary Failures, Efforts to Deceive FDA Inspectors

Posted 23 July 2013 | By Alexander Gaffney, RAC

Indian pharmaceutical manufacturer Wockhardt has not had an easy few months. A March 2013 inspection by the US Food and Drug Administration (FDA) resulted in an import alert for products manufactured at the company's Waluj, Aurangabad facility, and the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a massive recall for products manufactured at the same facility.

Clearly, something at the facility was amiss-something confirmed by the India Times earlier this week when it reported that FDA had finally sent the company a Warning Letter that would detail the extent of problems at the facility.

And according to the now-released Warning Letter, many of those problems are spectacular.

Efforts to Delay and Disrupt Inspection

"Your firm repeatedly delayed, denied, limited an inspection or refused to permit the FDA inspection," FDA states at the outset of the letter. FDA expanded its definition of what constitutes a delay, denial, limit or refusal of an inspection in a recent guidance document, and the letter appears to be one of the first - if not the first - instances of FDA applying that approach.

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.

In recent years, other Indian manufacturing companies, including Ranbaxy, have been accused of repeating studies until they get the desired results, and then discarding the undesirable test results-something likely on the minds of FDA investigators. And in yet another alleged incident involving the use of "unofficial batch record forms," (i.e. ones that could be discarded without necessarily being missed) a Wockhardt manager pressed by FDA said the practice was only used "one or two times." Meanwhile, other employees interviewed by FDA said the practice was actually mandated by that same employee, and was regularly reviewed by him personally. When confronted with that information by FDA, the manager then reportedly conceded having lied to the FDA official.

Myriad of Problems

Other highlighted incidents in the Warning Letter include:

  • The facility manufactured a product intended for US export, but did not tell FDA about its existence until investigators identified it themselves.
  • An FDA investigator pressed employees for access to quality control data and raw testing documentation for a tablet product manufactured at the facility "no less than six times," but the data was only provided to FDA during the close-out meeting several days later without any explanation.
  • FDA came across "approximately 75" unofficial batch records "torn in half in a waste area" confirming that many batches did not meet established visual inspection criteria. Those batches reportedly included "black particles, fibers, glass particles, sealing defects and volume variations."
  • Wockhardt informed FDA that out-of-specification products were not intended for consumption by US consumers when, in fact, they were destined for the US.
  • A Wockhardt employee admitted to using "other samples" to complete testing on an injectable drug
  • The facility contained a toilet facility that had urinals that did not use a pipe to carry urine away, but rather allowed it to drop onto the floor and into an open drain-20 feet away from the entrance to a clean room. "Stagnant urine was observed near the open drain," FDA wrote.

"The above examples raise serious concerns regarding the integrity, reliability and accuracy of the data generated and available at your facility," FDA wrote, demanding that the company provide an "independent and comprehensive evaluation of the extent and the deletion and destruction of records, a risk assessment regarding the potential impact on the quality of products, and a comprehensive corrective and preventive action plan."

"The lack of reliability and accuracy of data generated by your firm's laboratory is a serious CGMP deficiency that raises concerns with all data generated by your firm," FDA added later in the letter.

Warning Letter to Wockhardt

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