FDA 483 - Hybrid Pharma LLC - July 28, 2016

The FDA Form 483 details numerous deficiencies at a facility producing sterile injectable drug products. Key violations include inadequate procedures to prevent microbiological contamination, specifically media fills not representing maximum production lot sizes (e.g., media fills up to (b)(4) vials vs. production lots up to (b)(4) vials). The firm has not validated its (b)(4) for glassware depyrogenation.

Aseptic processing areas are deficient in cleaning and disinfection, with observed reddish/yellowish discoloration on HEPA filters and a (b)(4) filter without prior investigation. Disinfectant effectiveness studies have not been conducted for various cleaning solutions used. Cleanroom design is deficient, evidenced by black residue on ISO 5 Hood surfaces, improperly stored wipers, a ½” gap in an ISO 8/ISO 7 door, and blocked/taped low wall vents.

Personnel practices are inadequate; operator gowning touches the floor, and non-sterile coveralls entered the ISO 5 zone. Gloves were not changed or sanitized between cleaning different cleanroom areas and surfaces. Test methods for potency testing of sterile injectables are not validated.

Environmental monitoring is deficient, lacking continuous pressure monitoring with an alarm system and daily viable/non-viable environmental monitoring. Gloved fingertip and personnel gown testing are not performed daily. There is no written stability program for assigning beyond-use-dates greater than 60 days. Complaint and recall procedures are deficient, lacking criteria