FDA 483 - Patheon Italia S.p.A. - May 26, 2023

An FDA inspection conducted from May 18-26, 2023, at a sterile drug manufacturer in Monza, Italy, revealed significant deficiencies in compliance with Good Manufacturing Practices. The firm exhibited a deficient system for monitoring environmental conditions in aseptic processing areas, evidenced by repeated adverse microbial trends in personnel and environmental monitoring without effective mitigation strategies. Procedures designed to prevent microbiological contamination were found inadequate, specifically concerning media fills that did not scientifically simulate worst-case manufacturing operations for sterile products. Additionally, equipment, including a leak integrity tester for a restricted access barrier system, was not appropriately designed or qualified, lacking defined breach testing procedures and accurate timer calibration. The inspection also noted that drug products were not stored under appropriate temperature conditions, as warehouse temperature mapping studies were inadequate, failing to cover all representative storage locations and necessary probe heights. The manufacturer is required to provide a comprehensive response detailing corrective and preventive actions to address these critical observations and ensure product quality and patient safety.