FDA 483 - Downing Labs, LLC - October 09, 2015

An FDA inspection of Downing Labs, LLC from September 14 to October 9, 2015, identified significant deviations from current Good Manufacturing Practices (cGMP) for an outsourcing facility. The 14 observations detailed systemic failures across their sterile drug manufacturing and quality control operations.Key violations included a pervasive failure to thoroughly investigate unexplained discrepancies, such as numerous failing sterility test results for distributed injectable products, failed media fills, and out-of-specification chemical tests. Sterilization processes were found inadequately validated; media fills did not represent worst-case conditions, and critical sterilization equipment lacked proper documentation and assurance of effectiveness. Aseptic processing practices were deficient, with operators exhibiting poor technique, and environmental control systems for cleaning, disinfection, and monitoring were ineffective, evident by persistent microbial recoveries and uninvestigated adverse results.Furthermore, the company lacked established time limits for production phases, leading to high endotoxin levels in some products, and failed to adequately test "pyrogen-free" products. There were no specifications or testing for impurities, lyophilized product characteristics, or most non-sterile drug products. The facility also lacked a written stability program to support product Beyond-Use-Dates and preservative efficacy. Manufacturing processes and analytical test methods were not properly validated. Finally, product labels omitted required compounding information, and the facility failed to report all compounded products to the FDA. Downing Labs, LLC is required to implement comprehensive corrective actions to address these critical deficiencies.