FDA 483 - NerPharMa S.r.l. - June 19, 2024

An FDA inspection of drug manufacturer NerPharMa S.r.l. (Nerviano, Milan, Italy) from June 10-19, 2024, resulted in significant observations documented on a Form FDA 483, indicating deviations from Current Good Manufacturing Practices (CGMP). The primary concerns revolved around the control of sterile drug product manufacturing. Deficiencies included inadequate procedures to prevent microbiological contamination, such as incomplete aseptic process simulations, observed air turbulence, and absent airflow visualization studies for critical area changes. Aseptic techniques during mock filling were also found wanting, along with inconsistent cleaning schedules for Restricted Access Barrier Systems (RABS). Environmental monitoring in aseptic areas was deemed insufficient due to a lack of surface monitoring and incorrect personnel sampling. Furthermore, the firm failed to establish valid in-process specifications based on process variability, potentially impacting product quality. Other issues included inadequate written procedures and validation for equipment cleaning, insufficient equipment design qualification, and failures within the quality control unit regarding change control and corrective action follow-up. Employee training for visual inspection of critical defects was deficient, and batch production records lacked complete documentation of key operational steps. NerPharMa S.r.l. must formally respond to the FDA with detailed corrective and preventive actions to address these serious compliance issues.