FDA 483 - Advanced Accelerator Applications USA, Inc. - November 03, 2022

During an FDA inspection conducted from October 24 to November 3, 2022, Advanced Accelerator Applications USA, Inc., a sterile manufacturer, received several observations related to its adherence to regulatory requirements for drug manufacturing. Key issues included inadequate written procedures for critical production and process controls, such as incomplete equipment and performance qualifications for dose calibrators and environmental monitoring systems, with many periodic calibrations being overdue or not covering the full operational range of devices. The quality control unit demonstrated a failure to thoroughly follow established procedures, evidenced by a significant backlog of overdue investigations, a lack of written protocols for reviewing critical alarms, and unaddressed deficiencies in their alert reporting system. Furthermore, procedures designed to prevent microbiological contamination of sterile drug products were found to be insufficient, particularly concerning material transfer sanitization and uncompleted environmental monitoring qualifications. The firm also failed to adequately review unexplained discrepancies, including critical alarms during batch production that were neither documented nor assessed for product quality impact. The company is required to implement comprehensive corrective actions to address these findings and ensure compliance with Good Manufacturing Practices.