Intas Pharmaceuticals Limited — FDA Warning Letter Findings

Our investigators observed plastic bags filled with torn and discarded original CGMP documents in your quality control (QC) scrap area under a stairwell, in your general parenteral scrap room, and on a truck outside your facility. Among these CGMP documents were engineering checklists associated with the Environmental Monitoring System (EMS), torn Karl Fischer (KF) analytical test reports, auto titration curves, and analytical balance weight slips for finished drug products.

An analyst weighed out the same samples of amitriptyline hydrochloride tablets USP 100 mg batches multiple times for (b)(4) by (b)(4) test. The analyst stated to our investigator that he did not report all the test results, further stating that in some instances balance printouts were discarded in the trash. In addition, the time stamp on each of the analytical balance and (b)(4) printouts did not match your Laboratory Information Management System (LIMS) records. In your response, you commit to working with a qualified consultant to perform an overall baseline assessment of data integrity and governance controls, and to establish a remediation plan. Your response is inadequate in that it did not fully evaluate the scope of this deficiency and the impact to product quality. You did not adequately address the major failure of laboratory, operations, and quality assurance management to conduct proper oversight over documentation and prevent data integrity lapses. B. Your department failed to exercise appropriate controls over computerized systems. For example…

Your electronic batch records allowed changes to be made to manual entries prior to saving. Our inspector observed a production employee manually alter the reported time that an operation was performed. QA did not review audit trails as part of their batch record review to identify discrepancies and compare the reported date and time against that which was originally logged.

Destroyed KF raw data paper printouts associated with drug products were discovered by our inspection team in a trash bag. The KF instrument used for water content testing and assay testing is capable of storing electronic data; however, this capacity was not utilized, and you did not save this data electronically.

Your 2018 Process Equipment Assessment Report identified numerous gaps and deficiencies for electronic manufacturing equipment needing upgrades in access controls, audit trails, saving electronic data and preventing clock alterations. You had not documented closures of these corrective action and preventive action (CAPA) measures to support data integrity in your computerized systems. Your QA department had not performed a similar assessment in your QC laboratories. In your…

Analysts manually reprocessed chromatograms by adding integration events that were not approved by QC management. In addition, you lacked appropriate procedures describing when the analyst can manually input integration events, how these events should be used, or how they should be reviewed.

Your firm failed to establish and follow required laboratory control mechanisms (21 CFR 211.160(a)). Your firm failed to have appropriate procedures for the integration of chromatographic peaks and for the review of chromatographic data. Our inspection team identified examples of your analysts entering manual integration events that yielded passing results without adequate procedural controls or justification. In addition, your chromatographic data integration procedure is…

An analyst destroyed CGMP records by pouring acetic acid in a trash bin containing analytical balance slips for testing the standardization of (b)(4) . A QC employee stated he observed the same analyst destroy KF titration curves and balance printouts. The employee reported the incident to QC laboratory management on November 22, 2022. An investigation into the destruction of the torn CGMP documents and the impact to your drug product quality was not initiated until November 28, 2022.

You aborted hundreds of chromatographic sequences in your QC laboratories between January 2020 to November 2022. Each of the incidents were investigated by the quality control laboratory; however, you lacked adequate trending and CAPA systems to evaluate and identify recurring issues that should be targeted for laboratory improvements. In your response, you acknowledge the need to enhance your processes and practices for investigating laboratory deviations, applying CAPAs…

Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)). A. Your laboratory records lacked complete and accurate data to support the analysis performed. Colony forming units (CFU) were not counted accurately in the laboratory's environmental monitoring (EM) data. Our investigators observed colony counts shortly after being read by your…

Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22). You failed to ensure reliability of data relating to the quality of medicines produced at your facility. Our inspection revealed serious deviations, including but not limited to, inadequate oversight of original CGMP documents, deficient controls over computerized systems, insufficient laboratory investigations, and aborted chromatographic sequences. Senior facility managers failed to exercise their authority and responsibility to ensure reliable data, leading to severe data integrity deficiencies in your production and laboratory departments. These findings also indicate that your quality assurance function is not exercising its responsibilities, including but not limited to, oversight and control over the adequacy and reliability of CGMP data used throughout your operation. A. You failed to assure integrity of analytical testing data. Some examples include…

You invalidated multiple out-of-specification (OOS) results for (b)(4) USP without adequate scientific justification. You then prepared new samples and reported passing results. You concluded the OOS results may be due to (b)(4) contamination during initial sample preparation. However, the laboratory investigation, which was approved by QA, did not discuss why other samples in the same analysis of lots, from the same material, prepared by the same analyst, under the same test conditions, were not affected by such contamination.