FDA 483 - Alexion Pharma International Operations Unlimited Co. - January 24, 2023

Alexion Pharma International Operations Limited, a drug substance manufacturer in Dublin, Ireland, underwent an FDA inspection from January 16-24, 2023. The inspection resulted in several Form FDA 483 observations, indicating deficiencies in their manufacturing operations and quality systems, primarily related to current Good Manufacturing Practices (GMP). Key issues included a lack of assurance in contamination prevention, particularly concerning viral cross-contamination risks due to shared equipment and inadequate HVAC system evaluations. The firm also experienced recurring environmental monitoring excursions and cell culture contaminations, coupled with observations of technicians not adhering to aseptic techniques. Cleaning validation and sanitization programs were found to be deficient, lacking proper swab validation, comprehensive material assessments, and documented disinfectant contact times, alongside unvalidated equipment hold times. Further observations highlighted inadequate controls over electronic data acquisition systems, with audit trails not being reviewed and potential conflicts of interest in system administration. Numerous instances of procedural non-compliance were noted, affecting sample handling, labeling, calculation accuracy, and environmental monitoring record-keeping. The quality unit's oversight was deemed insufficient, evidenced by un-audited critical service contractors, incomplete corrective actions for assay trends, missing batch record pages, untrained personnel signing critical documents, and incorrect instrument date/time settings. These findings necessitate Alexion Pharma International Operations Limited to implement comprehensive corrective and preventive actions to ensure compliance with GMP regulations and prevent product quality impact.