FDA 483 - Pharmedium Services, LLC - May 26, 2016

This FDA Form 483 details significant deficiencies at an outsourcing facility producing sterile drug products. The facility's aseptic processing areas, including ISO-5 laminar flow hoods and an ISO-7 Clean Room, lack adequate systems for maintaining aseptic conditions.

Key violations include: * **Environmental Control Deficiencies:** Uncalibrated pressure gauges for ISO-5 hoods, lack of continuous monitoring for ISO-7 HEPA units, and failure to consistently maintain positive pressure cascade from the ISO-7 Clean Room, with documented negative pressure excursions and no investigations. * **Aseptic Process Validation:** Smoke studies under dynamic conditions did not fully represent routine operations or personnel movement, and failed to demonstrate consistent airflow from the ISO-7 Clean Room when doors were opened. * **Product Testing Deficiencies:** Sterility testing is not performed for every batch of finished sterile drug product, with a significant percentage of batches not submitted for testing or having delayed results received after product expiration. Potency testing is also deficient. * **Cleaning and Disinfection:** Lack of scientific justification for the effectiveness of the sporicide and its contact time. * **Quality Control and Inspection:** Inadequate visual inspection process for particulate matter, no qualification process for visual inspection personnel, and no representative defect library for training. * **Component Control:** Incoming sterile components are not sampled, tested, or released by quality control, and supplier Certificates of Analysis are not routinely reviewed for critical attributes.