FDA 483 - Janssen Vaccines Corporation - November 19, 2024

During an inspection from November 11-19, 2024, the FDA issued a Form 483 to Janssen Vaccines Corporation, a drug product manufacturer based in Incheon, Korea. The observations detailed significant deviations from Good Manufacturing Practices (GMP), affecting quality control, aseptic processing, and equipment qualification. Specifically, the company failed to follow its own procedures for reporting product quality issues to regulatory authorities. Despite receiving at least 25 market complaints about stopper quality for distributed products between November 2023 and November 2024, the firm did not submit required reports, attributing the defects to end-users rather than manufacturing. Furthermore, procedures to prevent microbiological contamination during sterile drug product manufacturing were not consistently followed. This included undocumented and prolonged interventions during vial filling using unapproved tools and methods, operators working with fogged eye protection, and improper handling of tools in critical aseptic areas, all contradicting established operational guidelines. Aseptic processing areas also showed inadequate systems for maintaining sterile conditions. Non-viable particle monitoring lacked sufficient coverage to ensure a Grade A environment. Additionally, smoke studies revealed turbulent airflow patterns, failing to demonstrate the necessary unidirectional airflow for aseptic processes. Equipment cleaning and disinfection procedures were found deficient, highlighted by a stopper transfer pipe with a rough, cracked weld and a discolored, shedding internal surface. This condition was linked to a product complaint regarding uncharacteristic product color, for which no root cause was determined. Finally, critical integrity test machines used in manufacturing were inadequately qualified. Essential operational parameters and ranges were not properly qualified on-site, with the company relying on vendor data and performing only single-point verifications. This issue contributed to failed integrity test results for certain manufactured batches. Janssen Vaccines Corporation is required to submit a detailed written response to the FDA outlining comprehensive corrective and preventive actions to ensure full compliance with regulatory standards.