FDA 483 - Carolina Infusion - August 12, 2022

During an inspection conducted from July 18 to August 12, 2022, the U.S. Food and Drug Administration (FDA) issued a Form FDA 483 to Carolina Infusion, a producer of sterile and non-sterile drug products. The observations detailed significant concerns regarding the firm's manufacturing processes and quality controls, particularly impacting drug product safety and sterility. Key violations included a critical lack of endotoxin control for intrathecal drug products. Carolina Infusion failed to verify materials for endotoxin, did not release products based on endotoxin limits, and distributed thousands of intrathecal prescriptions without endotoxin testing for nearly a month due to equipment maintenance. Additionally, bulk drug substances lacked endotoxin data, and the firm inappropriately pooled samples for testing, yielding unreliable results. Further issues highlighted inadequate aseptic processing, as media fills were not performed under sufficiently challenging conditions, questioning the firm's ability to maintain sterile environments. The ISO-5 classified areas for sterile compounding were not certified under dynamic operational conditions. Crucially, the facility exhibited inadequate pressure differentials between controlled and uncontrolled areas, with viable air sampling revealing pathogenic organisms like Trichophyton sp. and Staphylococcus exceeding action limits in critical areas, directly impacting product sterility. Lastly, non-pharmaceutical grade components were used in non-sterile drug product formulations. These observations indicate a need for Carolina Infusion to implement comprehensive corrective actions to align with regulatory expectations for drug manufacturing, ensuring product quality and patient safety.