FDA 483 - PharMEDium Services, LLC - December 22, 2017

This FDA Form 483 details significant deficiencies at an outsourcing facility, impacting its quality control, manufacturing, and laboratory operations.

**Key Violations and Observations:**

* **Quality Control Unit Deficiencies:** The quality control unit lacks the authority to reject drug products. * **Contamination Control Issues:** The facility layout is not designed to prevent contamination. Procedures for preventing microbiological contamination of sterile drug products are inadequate, lacking proper validation of aseptic processing. * **Investigation Failures:** The firm failed to thoroughly investigate unexplained discrepancies or batch failures, including incomplete investigations into 2017 sterility failures (e.g., no microorganism identification, no assessment of affected lots). A root cause was not determined for a Ropivacaine HCl lot that failed endotoxin testing. Investigations into over 100 microbial excursions in ISO 5 hoods (Aspergillus species) and 289 confirmed Out-of-Specification (OOS) potency results since January 2017 were incomplete or not closed, with corrective actions not implemented for the microbial excursions. * **Aseptic Processing Area Deficiencies:** Systems for maintaining equipment, cleaning/disinfecting rooms, and monitoring environmental conditions in aseptic processing areas are deficient. Environmental monitoring revealed the presence of Aspergillus, Cladosporium, and Rhizopus in ISO 5 hoods. * **Laboratory Control Issues:** Laboratory controls lack scientifically sound test procedures. Drug product samples for conformance testing are not