Novartis Pharmaceuticals Corporation – FDA EIR, Apr 7, 2017

Novartis Pharmaceuticals Corporation underwent a Pre-License Inspection by the FDA's Center for Biologics Evaluation and Research (CBER) from April 3-7, 2017. This GMP inspection supported the Biologics License Application for Tisagenlecleucel-T (CTL019), an autologous cell therapy product. The inspection, focusing on the Morris Plains Cell and Gene Therapy Facility, evaluated manufacturing operations, facilities, equipment, and quality control systems for this critical B-cell acute lymphoblastic leukemia treatment.

At the conclusion, a Form FDA 483 was issued, highlighting significant objectionable conditions. Key violations included incomplete process validation for CTL019 manufacturing. Specifically, the process performance qualification (PPQ) study relied on clinical batches preceding the commercial process definition, and critical changes to the commercial manufacturing process were not adequately evaluated during validation. Furthermore, hold steps were not defined in the Master Batch Record. A second major issue was the failure to initiate deviations, investigate, or determine root causes for numerous microbial monitoring action level excursions involving ISO operators between Q1-Q3 2016. These findings necessitate prompt corrective actions from Novartis to ensure compliance with regulatory standards for the product's licensure and commercial distribution.