Nelson Laboratories, LLC – FDA 483, Mar 22, 2024

During a recent FDA inspection, a pharmaceutical firm received an FDA Form 483 detailing significant deviations from Current Good Manufacturing Practice (CGMP) regulations, specifically 21 CFR Part 211. The observations primarily concern the manufacturing of sterile drug products and necessitate comprehensive corrective actions. Key violations included the firm's failure to establish and follow adequate procedures to prevent microbiological contamination. This was evidenced by the absence of dynamic smoke studies for critical aseptic operations, such as sterile connections and stopper additions, which are essential to demonstrate unidirectional airflow. The environmental monitoring program was deficient, particularly in not monitoring the capper chute for microbial presence. Personnel practices were also cited; operators' goggles used in aseptic areas were not evaluated for their contamination potential, and environmental monitoring analysts lacked proper training for sampling difficult locations. The quality control unit exhibited a lack of authority by accepting and using stopper lots that failed particulate matter specifications, despite recurring issues. Investigations into out-of-specification particulate matter results were found inadequate, often closing without identifying root causes or implementing effective follow-up. Furthermore, the firm failed to validate critical manufacturing processes, notably for Epinephrine Injection, USP, which repeatedly experienced media fill failures and particulate matter issues. Lastly, cleaning and maintenance procedures were insufficient, as the effectiveness of the sanitizing agent used in the ISO 5 aseptic processing area had not been scientifically demonstrated. These observations collectively indicate a systemic need for the firm to enhance its quality systems to ensure drug product sterility and overall quality.