Teva Parenteral Medicines, Inc. – FDA 483, Jul 10, 2015

During an inspection conducted from July 13 to July 24, 2009, Teva Parenteral Medicines INC in Irvine, CA, received an FDA Form 483 citing significant deviations from Current Good Manufacturing Practices (cGMP). The observations highlighted critical shortcomings across multiple systems, primarily affecting product quality and sterility assurance. Key violations included a deficient quality control unit that failed to ensure proper procedure approval and lacked adequate oversight of manufacturing processes. Specifically, media fills for aseptic operations, essential for sterility assurance, had not been performed for over a decade. The firm also demonstrated inadequate investigations into bacterial endotoxin contamination, often deeming root causes "unknown" without implementing corrective actions. Product release procedures were found lacking, with no assurance that drug products were free from bacterial endotoxin, as evidenced by failed re-testing of distributed lots. Further issues involved inadequate in-process material testing, unrepresentative finished product sampling, and a failure to thoroughly investigate unexplained discrepancies or extend investigations to other potentially affected batches. Equipment design, cleaning, and maintenance procedures were also cited, including the use of cleaning agents ineffective against endotoxins, unvalidated cleaning processes, and numerous instances of bacterial endotoxin recovery in water systems without effective remediation. Personnel monitoring for microbial contamination in critical areas was also found to be insufficient. These observations indicate a systemic failure to maintain appropriate controls for drug product manufacturing, potentially compromising product safety and quality. Teva Parenteral Medicines is required to provide a comprehensive response detailing corrective and preventive actions to address these serious deficiencies.