FDA EIR - Novartis Pharmaceuticals Corporation - August 21, 2019

An FDA inspection of Novartis Pharmaceuticals Corp in Morris Plains, NJ, was conducted from August 13-21, 2019. This Level 1 inspection focused on the manufacturing operations of Kymriah (tisagenlecleucel), an autologous cell therapy product, under the regulatory framework of the Team Biologics FY’2019 work plan and Compliance Program 7345.848(F) for Biological Drug Products. The inspection resulted in an FDA Form 483, detailing several significant observations. Key issues included inadequate stability data for Kymriah, with some product lots failing cell viability tests at 6 and 9 months, indicating potential shelf-life instability. Novartis was cited for not adequately establishing the stability profile for a specific manufacturing version of Kymriah and for failing to assess product lots that did not meet cell viability criteria, contrary to their own procedures. Furthermore, an investigation into a cell viability out-of-specification trend lacked a comprehensive corrective and preventative action (CAPA) plan. Other observations highlighted a lack of data supporting the qualification of critical raw materials, disinfectant agents failing validation criteria, and deficiencies in aseptic processing. The implemented CAPAs for cell viability failures were deemed ineffective, and the firm exhibited systemic weaknesses in CAPA management, including a failure to establish timely implementation, evaluate effectiveness, and properly close actions. Additionally, the company did not consistently identify out-of-specification stability trends, and its periodic review procedures lacked detailed CAPA assessments. Novartis management committed to providing a formal response to the FDA within 15 business days to address these findings.