FDA 483 - Xellia Pharmaceuticals USA LLC - December 15, 2022

The FDA issued a Form 483 to Xellia Pharmaceuticals USA LLC following an inspection conducted from November 28 to December 15, 2022. The inspection of this sterile drug product manufacturer revealed significant deficiencies in its quality control, aseptic processing, investigation procedures, and computer system controls, indicating non-compliance with current Good Manufacturing Practices (cGMP) as outlined by the Federal Food, Drug, and Cosmetic Act.Key observations highlighted the Quality Unit's failure to provide adequate oversight, particularly regarding aseptic controls and identifying deviations. The company approved manufacturing operations without conducting required aseptic process simulations (media fills) after maintenance shutdowns, specifically for a Vancomycin filling line, leading to the release of three drug lots without this critical validation. Furthermore, the firm failed to perform necessary risk assessments to determine the need for media fills following periodic maintenance, contrary to its own written procedures.Investigations into manufacturing discrepancies were also found lacking; for instance, a media fill campaign that resulted in numerous units with "particulate/precipitation" led to an insufficient subculture sampling plan, identifying bacterial growth but failing to thoroughly assess the extent of contamination. Additionally, issues with computer system controls were noted, including the use of a common, non-password protected login for a critical instrument with disabled 21 CFR Part 11 functionality, and enabled delete functions for all users on another analytical system.To address these findings, Xellia Pharmaceuticals USA LLC must implement comprehensive corrective and preventive actions, focusing on strengthening its quality system oversight, validating aseptic processes, ensuring robust investigation practices, and improving data integrity controls across its manufacturing operations.