FDA 483 - Celltrion Inc. - February 27, 2024

Celltrion Inc. received an FDA Form 483 following an inspection from February 19-27, 2024, at its drug manufacturing facility in Yeonsu, Incheon, Korea. The inspection revealed significant concerns regarding the firm's adherence to Current Good Manufacturing Practices (CGMP). Key violations centered on deficiencies in aseptic processing and sterility assurance. Specifically, media fill studies for certain vial sizes were deemed inadequate, and environmental monitoring in critical areas showed microbiological excursions, including mold and yeast, which were not comprehensively investigated, yet associated batches were shipped to the U.S. The biosafety testing laboratory demonstrated poor documentation practices, a high risk of cross-contamination between cell lines, and unlabeled equipment. Aseptic filling operations exhibited multiple procedural breaches, such as operators touching sterile components with non-sterile gloves and inadequate disinfection protocols. Critically, the Quality Unit failed to follow established procedures, including the observed shredding of original control documents (analytical, batch, training records) and executed batch records without proper tracking or deviation initiation, raising serious data integrity concerns. Drug substance manufacturing lacked adequate controls to prevent contamination and cross-contamination, highlighted by deficient risk assessments, poor facility maintenance, and an ineffective cleaning and sanitation program. The environmental monitoring program also lacked robust measures for fungal and spore-forming bacteria. Finally, the firm's determination of product conformance was found deficient, with questionable HPLC/UPLC equilibration runs and numerous unexplained aborted analytical runs, impacting data reliability. Celltrion Inc. is required to provide a robust response addressing these serious observations.