FDA 483 - Downing Labs, LLC - July 16, 2014

The FDA conducted an inspection of Downing Labs, LLC, a producer of sterile drug products, from June 3 to July 16, 2014. The inspection revealed 15 observations regarding the facility's compliance with manufacturing and quality control standards.

Key violations include: - **Inadequate Investigations:** Failure to thoroughly investigate 22 instances of sterility or endotoxin failures in drug product lots between April 2013 and June 2014. Investigations were either absent or incomplete, with some failed lots (e.g., Cyanocobalamin lot #N04302014@14) re-sterilized and pending distribution, while others (e.g., Folic Acid lot #N04172014@20) were quarantined for destruction. - **Microbiological Contamination Prevention:** Procedures to prevent microbiological contamination were not established. Media fills were not representative of actual production (e.g., failing to simulate maximum vial numbers, interventions, or aseptic equipment assembly). Positive controls for media fills were not inoculated with known organisms, and media fills for lyophilized products were not conducted. Sterilization processes for injectable drug products were not validated. - **Environmental Monitoring Deficiencies:** Aseptic processing areas lacked adequate environmental monitoring. Incoming prepared media was not monitored, surface samples were obtained randomly without identified areas, and routine personnel monitoring was infrequent with no gown monitoring. - **