FDA EIR - Novartis Pharmaceuticals Corporation

An FDA Pre-License Inspection (PLI) was conducted at Novartis Pharmaceuticals Corporation's Cell and Gene Therapy Facility in Morris Plains, New Jersey, from April 3-7, 2017. The inspection, performed by the Center for Biologics Evaluation and Research (CBER), supported the review of Biologics License Application (BLA) 125646/0 for Tisagenlecleucel-T (CTL019), an autologous cell therapy product for pediatric and young adult patients with acute lymphoblastic leukemia. The inspection focused on manufacturing operations, facilities, equipment, and quality controls for the CTL019 drug product. At its conclusion, a Form FDA 483 was issued, detailing two main objectionable conditions. Firstly, process validation for CTL019 manufacturing was found incomplete. This included the process performance qualification (PPQ) study being based on clinical batches made before commercial processes were defined, and significant changes to the commercial manufacturing process (e.g., leukapheresis materials and methods) not being evaluated during validation. Additionally, hold steps were not clearly defined in the Master Batch Record. Secondly, the inspection noted that deviations were not initiated for numerous action level excursions related to microbial monitoring of operators during 2016, and these excursions were not properly investigated to determine root causes. Novartis is expected to address these observations.