FDA WARNING_LETTER - Tubilux Pharma Spa - December 09, 2016

The FDA issued a Warning Letter to Tubilux Pharma S.p.A. following an inspection from December 1-9, 2016, identifying significant CGMP violations for finished pharmaceuticals, rendering their drug products adulterated.

Violations include: 1. **Equipment Design and Airflow (21 CFR 211.63):** Turbulent airflow was observed in aseptic processing line smoke studies (September 2015, December 2016), posing a contamination hazard. Unidirectional airflow was not established where caps are applied. Dynamic smoke studies showed turbulent airflow during manual loading of sterile components, and operators performed manually intensive aseptic activities with significant interventions. The FDA requires identification of all contamination hazards, a formal risk assessment of process, equipment, and facility hazards, and a comprehensive CAPA plan.

2. **Laboratory Controls and Particulate Testing (21 CFR 211.160(b)):** The firm failed to test ophthalmic products for particulates prior to release, despite observing high particle count alarms. The FDA requires an implementation plan for particulate matter testing, revised drug product specifications, and a written procedure for in-process inspection of visible particles.

Additional CGMP deficiencies noted include: * **Sterility Testing:** The use of a (b)(4) cycle for sterility test samples may compromise validity by killing or injuring organisms. A CAPA is required to remediate this. *