Contract API Manufacturer Smruthi Organics Receives FDA Warning LetterBy
The Indian contract manufacturer Smruthi Organics Ltd received a Warning Letter (dated March 6, 2014) from FDA for current good manufacturing practices (cGMP) violations in the manufacture of active pharmaceutical ingredients (APIs) at its facility in Chincholi Village, Taluka Mohol, Solapur, India, based on an inspection of the facility made on October 15 to 18, 2013. FDA noted that the firm’s response to the violations, dated November 4, 2013, lacked sufficient corrective actions.
The firm was cited for failure to maintain complete and accurate laboratory test data generated in the course of establishing compliance of APIs to established specifications and standards. Specifically, the firm was cited for not having written explanation for deletion events observed on audit trails for its standalone high-performance liquid chromatography (HPLC) units. The company’s standard operating procedures did not include instructions for the retention of electronic raw data. Furthermore, laboratory test data did not include records of the integration parameters used for any HPLC analyses. The agency said there also were incomplete raw data to support the test method validation/verification activities for the test methods used for the company’s APIs, including new test method validation/verification data for residual solvents testing that was requested during the inspection. The agency also cited the firm for performing trial injections for HPLC analyses prior to running the release and stability tests that are then reported.
Investigators also identified calibration and media preparation records that were not authentic in that the persons that signed each record as having performed the activity were not at work on the day the work was accomplished.
Additionally, the firm was cited for failure to maintain and make available for inspectional review production and control records for currently marketed APIs. The agency noted that a February 2013 European Directorate for the Quality of Medicines inspection found that the firm was blending out-of-specification API batches with other API batches.The head of quality assurance and regulatory affairs stated to the investigator that the relevant records had been destroyed but the company’s written response states that there was a miscommunication during the inspection and that these records had not been destroyed.
The firm was also cited for inadequate investigations of critical deviations or failure of a batch to meet its specifications or quality standards. Specifically, the agency note that investigation on June 7 and June 18, 2912 cited particulate matter in nine API batches.
The firm was also cited for data-integrity issues and was asked by FDA to provide in its corrective action plan, its commitment, procedures, actions, and controls to ensure data integrity.The agency recommended hiring a third-party auditor with experience in data-integrity problems to assist in this evaluation and overall cGMP compliance.The agency asked the firm to provide a list of all the lots of APIs shipped to the United States where release relied upon non-existent, inaccurate, or unreliable test data.