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The Indian facility was cited for a range of quality and data integrity violations.
FDA issued a warning letter to Pan Drugs Limited on August 25, 2016 following an inspection of the company’s Vadodara, India facility that occurred from Nov. 30–Dec. 3, 2015. The company was cited for violations of current good manufacturing practices (CGMPs) that included inadequate quality control, unsanitary conditions, and improper control over computer systems. The company was placed on Import Alert 66-40 by FDA on Dec. 8, 2015.
According to FDA, adulterated API manufactured at the company’s Nandesari facility, which was put on an FDA import alert on May 5, 2015, was used in the manufacture of product shipped to the US market from Oct. 7-Nov. 23, 2015. The company’s quality unit also approved certificates of analysis (COA) for product before conducting all quality control and release testing. The warning letter stated that the “production manager falsified the documents by signing and dating the ‘Prepared By’ and ‘Checked By’ sections of the COA.” FDA stated, “According to your response, you recognized that these practices were not adequate. You intended to implement a signature list and revise your SOPs to address these failures. However, these actions do not address the quality unit failures observed.”
Furthermore, the company’s facilities were found to be inadequately maintained. Investigators were told that the company did not have cleaning procedures for the equipment or facility. Mold-like substances on the walls of processing areas and gaps and holes in walls where pests and vermin might enter were found. A lizard was observed by inspectors in the facility and evidence of other pest activity was seen. Rust, dirt, and lubrication leaks were observed on shared drug manufacturing equipment.
FDA asked the company to “provide details of the plan you stated you will develop for facility upgrades and corrections, including photographic evidence that demonstrates that the entire facility meets CGMP requirements. Your response should also include your plan to ensure your facility and equipment will be proactively maintained in such a way that your product is continually manufactured under CGMP conditions.”
In addition to the quality issues, FDA found that the company had inappropriate control over computer and related systems. Unauthorized personnel had access to master production and control records. FDA stated the company should perform a comprehensive investigation of the inaccuracies in data records and reporting that includes a detailed investigation of protocol and methodology; interviews with current and former employees; an assessment of the extent of data integrity deficiencies; and a comprehensive retrospective evaluation of the nature of data integrity deficiencies.
FDA stated the company should also perform a current risk assessment of the potential effects of the observed quality failures that should include an analysis of patient risk. The agency asked the company to provide a global corrective action and preventive action plan (CAPA) that includes steps for ensuring relability and completeness of all data; description of root causes of data integrity lapses; actions taken to ensure quality of drugs; long-term measures describing remediation efforts and enhancement of all procedures and processes; and a status report of all CAPA activities.
In addition to the data integrity and quality issues, the company also attempted to delay FDA’s inspection and did not provide the agency with all requested records, which is cause to consider the drugs as adulterated. In the letter, FDA stated, “On November 30, 2015, our investigator observed your warehouse supervisor tearing out pages from your firm’s annual report and placing the pages into his pocket. Eventually, the supervisor provided the pages to our investigator. On December 1, 2015, our investigator requested printed chromatograms from your HPLC and GC. You failed to provide them.”
FDA stated in the letter that it may refuse admission of the company’s products manufactured at the facility if the violations are not corrected. FDA may also withhold approval of new applications or supplements listing the company as a drug product manufacturer.