FDA 483 - NerPharMa S.r.l. - June 27, 2025

During an FDA inspection conducted from June 16 to June 27, 2025, drug manufacturer NerPharMa S.r.l. in Nerviano, Milan, Italy, was issued an FDA Form 483 due to significant observations related to their aseptic processing and sterilization validation for sterile drug products. The core issue highlighted was the inadequacy of procedures designed to prevent microbiological contamination. Inspectors observed that interventions during aseptic processing were not consistently documented in batch production records, impacting the representativeness of media fills. Additionally, the media fill approach itself was deemed unrepresentative of routine operations, and vials designated for sterility testing were not subjected to required inverted incubation conditions.

Further critical observations from smoke studies and video reviews revealed poor aseptic practices and failures in maintaining unidirectional airflow within critical processing areas. These included the absence of smoke studies for specific Grade A laminar airflow units, instances of turbulent airflow, and operators repeatedly blocking “first air” to open vials and sterile components with their hands and arms during various operations, without subsequently rejecting the impacted products. A recent modification to the vial filling line also lacked validated integrity testing procedures.

NerPharMa S.r.l. is required to address these inspectional observations by implementing comprehensive corrective actions to ensure full compliance with regulatory expectations for sterile drug manufacturing and to safeguard product sterility.