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Warning letters, 483s, Recalls, Import Alerts, Audit observations
Warning letters, 483s, Recalls, Import Alerts, Audit observations
Janssen’s Korean Vaccine unit Janssen Vaccines Corporation (FEI 3012637764) received an USFDA 483 for critical cGMP deviations. The site was inspected by USFDA investigator Rajiv R Srivastava in November 2024. The USFDA 483 cited aseptic processing practices were not in control and complaint handling was lacking. The 483 report included five key observations.
Aseptic Operations Not in Control
Aseptic operations, practices, and areas were deficient to control aseptic conditions. Procedures to prevent microbiological contamination of sterile drug products were not adequately defined or followed.
During audit multiple interventions were observed during vial filling operations which were not part of established procedures. When vials got stuck during filling, the validated intervention involved using gloves and tweezers. However, the actual intervention required multiple adjustments, such as loosening, wiggling, and transferring a pair of extra-long hemostat tweezers, taking much longer than simulated in media fill studies. The QC head initially insisted the intervention was a regular one before finally opening a non-conformance. Operators were also observed fully inserting the tips of the tweezers inside the jammed vials and rubbing the tweezers against the wall of the tweezer holder when placing them back.
The aseptic processing areas had deficiencies in maintaining, cleaning, and disinfecting equipment used to control aseptic conditions. Issues were noted with non-viable particle (NVP) monitoring and airflow patterns. The NVP counters placed in the center did not provide adequate coverage to ensure Grade A conditions around and over the critical areas and vials. Smoke studies failed to demonstrate unidirectional airflow (UDA) patterns in several instances with insufficient smoke to verify UDA. Additionally, the stopper transfer pipe had rough welding and cracks, and the integrity test machines were not adequately qualified.
Complaint Handling
The firm failed to follow its procedures for handling product quality complaints and reporting Biological Product Deviation Reports (BPDR or FAR). Firm’s SOP mandated notification to Health Authorities when there were two or more complaints with the same defect and root cause for the same lot, with or without a signal. The firm had several instances of 2, 3, or 4 complaints for the same lot with similar defects. Management claimed the defects were not related to the manufacturing process, and thus no CAPA was implemented.
The observations in the FDA Form 483 serve as a clear reminder of the need for regular monitoring of aseptic operations, prompt identification of non-routine interventions, thorough risk assessments, and implementation of corrective actions. It also underscores the importance of regular operator training and awareness build up focussing on acceptable and non acceptable practices.
USFDA 483 Janssen Vaccine Corporation (South Korea, November 2024)
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