Amid ongoing efforts by the US FDA to crack down on foreign suppliers not meeting cGMP (current good manufacturing) requirements, India-based Sun Pharma is the latest company to be hit with a warning letter.
The FDA said in its warning letter from earlier this month, which comes as Sun has also been issued an import alert over cGMP issues, that Sun is missing “fundamental raw data and information necessary to document” its analyses. In addition, Sun seems to have taken on a practice whereby it unofficially tests samples and then discards the results while reporting results from other tests.
“For example, during stability testing, your firm tested a batch sample six times and subsequently deleted this data,” the agency says, noting that such a practice not only impacts the integrity of this data but of other data collection efforts by the company.
FDA investigators found Sun performed initial “trial” sample high performance liquid chromatography (HPLC) analyses prior to acquiring the “official” analyses, while “trial” sample results were discarded.
Similar unacceptable data handling practices were observed in the laboratory’s conduct of gas chromatography (GC) analyses as the FDA investigators reviewed data from “unofficial” injections for GC analyses.
What’s perhaps worse is that Sun’s senior QC (quality control) officer confirmed FDA’s suspicions that QC laboratory employees had frequently practiced the use of “trial” injections at the facility in Gujarat. In total, the FDA’s inspection found 5,301 deleted chromatograms on a computer used to operate two HLPC instruments.
In addition, the inspection revealed numerous examples of deleted GC electronic raw data files on the computer controlling the GC instruments that were replaced with identical “official” chromatogram file names. The identically named GC data files that were deleted had been created at different times and contained disparate data.
The examples outlined in the warning letter, according to the agency, “suggest a general lack of reliability and accuracy of data generated by your firm's laboratory, which is a serious CGMP deficiency that raises concerns about the integrity of all data generated by your firm. We are concerned that your laboratory allowed the practice of ‘trial’ injections and deletion of both GC and HPLC files to persist without implementation of controls to prevent data manipulation until at least September 2013.”
Meanwhile, Sun also seems to have been attempting to destroy raw data. During the inspection, the investigators found approximately 10 waste bags containing torn or partially destroyed raw data CGMP records related to a variety of manufacturing activities.
Contract employees were also not trained in CGMP or in job-specific procedures, investigators found. cGMP documents, including procedures and batch records, “apparently could not be fully comprehended by many of the contract employees,” the FDA said.
In order to respond to the FDA, the agency calls on the company’s corporate management to “immediately undertake a comprehensive evaluation of global manufacturing operations to ensure compliance with CGMP regulations. We strongly recommend that you hire a qualified third party auditor with experience in detecting data integrity problems to assist you with this comprehensive evaluation.”
Sun Pharma did not respond to a request for comment on whether it has responded to the warning letter.