Region Care, Inc. – FDA 483, Jun 10, 2016

During an inspection, the FDA observed significant deficiencies at a facility producing sterile drug products. The procedures for preventing microbiological contamination lacked adequate validation of the sterilization process. Smoke studies, conducted by a vendor, were not performed under dynamic conditions, failing to assure uninterrupted laminar airflow during aseptic operations. HVAC returns in the cleanroom were obstructed by wire racks and garbage cans.

Sterile drug products, including those prepared from non-sterile starting materials (morphine, hydromorphone, bupivacaine, baclofen), were not tested for sterility, pyrogens, or conformance to specifications prior to release. Environmental monitoring in aseptic processing areas was deficient, with work surfaces inside ISO-5 workstations not sampled daily, and viable air sampling not performed daily during aseptic operations.

Magnehelic gauges and temperature monitoring equipment in the ISO-7 anteroom and walk-in refrigerator were not calibrated, with some last calibrated in March 2014. There were no written procedures or documentation for visual checks of sterile drug products for clarity, discoloration, or particulates. Routine equipment calibration was not performed according to a written program.

Personnel clothing for sterile compounding was inappropriate, and sterile gowns were reused throughout the day. Investigations into environmental monitoring excursions (single colony growth from surface and floor samples) were inadequate. There was a failure to thoroughly review unexplained discrepancies or batch failures to meet specifications.