FDA 483 - California Pharmacy & Compounding Center - August 31, 2016

The FDA Form 483 details observations from an inspection of an outsourcing facility. Key deficiencies relate to sterile drug product manufacturing and labeling.

**Sterilization Process Validation:** * **Media Fills:** Inadequate, failing to simulate worst-case scenarios (e.g., longest production times, human interventions) as per WI-101-003-003. Specific examples include Bevacizumab PFS production not meeting maximum filling time. Growth promotion challenges lacked gram-negative bacteria and in-house representative isolates. Incorrect media was used for Lidocaine HCL/Phenylephrine HCL media fill. Rejected vials/syringes with particulates/defects were not included in incubation. * **Smoke Studies:** Conducted on (b) (4) for ISO 5 Laminar Flow Hoods, but not under dynamic conditions. They failed to assure unidirectional airflow under working conditions and ingress prevention of ISO 7 air into ISO 5. Components/equipment (e.g., (b) (4)) and operator movements were not included.

**Environmental Monitoring & Air Supply:** * **Personnel Monitoring:** Lacks scientific rationale to assure aseptic processing. Samples (e.g., around (b) (4)) were taken (b) (4). * **HEPA Filter Certification:** (b) (4) certifications for ISO 7 and ISO 8 rooms did not include HEPA filter leak testing for filters