FDA investigators identified significant violations of cGMP regulations for finished pharmaceuticals during inspections from Oct. 29 to Nov. 1, 2013 at the Kheda, India manufacturing facility of Marck Biosciences, according to an FDA warning letter dated July 8, 2014. Violations included issues with record keeping, employee training, and product labeling, as well as failure to maintain buildings in a clean and sanitary condition.
FDA noted discrepancies between unofficial and official visual inspection records and requested that the company describe controls to prevent data manipulation by operators and supervisors. FDA also found that production personnel used scratch paper for documenting cGMP-relevant data, which is not acceptable under cGMP. In addition, "The discrepancy between your destruction records and your quarantine records provide further evidence that your documentation is not accurate and reliable," noted FDA in the warning letter. The company also failed to maintain adequate written records of major equipment maintenance.
At the time of inspection, FDA found that contract employees had not received training on cGMP and that documents regarding cGMP training had been falsified. The company did not follow written procedures regarding storage and warehousing of drug products, and units could not be located when requested during the inspection. FDA requested in the warning latter that the company, "provide evidence that these units were released by your quality unit prior to being distributed. Also describe any new procedures intended to achieve full accountability and control over all products in your facility, and describe any controls in place to prevent unauthorized product shipments. In addition, provide an explanation for the torn records found by the investigator, describe your document retention policies, and include details of any corrective and preventive measures you are implementing to address FDA’s discovery of these destroyed records." In addition, investigators found numerous loose and uncontrolled labels for multiple products in the open office area adjacent to the packaging lines. Unused labels were not stored in a manner to prevent mix-ups or mislabeling.
FDA found that Marck Biosciences did not maintain buildings according to cGMP. Investigators found mold growth in the washroom located at the entry to the sterile manufacturing area and numerous dead insects in the “Sample Pass Through” room near a sterile filling line. The letter also noted that an MHRA report of a December 2013 audit conducted at the facility found fungus growth within a large volume parenteral product manufactured at the facility.
In the warning letter, FDA wrote, "We expect that you hire a third-party auditor, with experience in detecting data integrity problems, to assist you with this evaluation and assist with your overall compliance with CGMP. It is your responsibility to ensure that data generated during operations is accurate and that the results reported are a true representation of the quality of your drug products."