Case Studies and Recommendations on CMC Changes of Autologous CAR-T Cell Therapy Products
In recent years,research in the field of chimeric antigen receptor T(CAR-T)cell therapy in China has been active.Due to the rapid iteration of technologies in this field,complex manufacturing processes,and relatively limited experience in pharmaceutical research and changes,the evaluation,research,submission,and review of chemistry,manufacturing,and controls(CMC)changes in CAR-T products present various challenges for both companies and regulatory agencies.The Cell and Gene Therapy Products Committee of the China Society for Drug Regulation organized a task force comprising several leading domestic cell therapy companies to focus on case studies and common challenges related to CMC changes in autologous CAR-T products.The group conducted industry surveys,collected regulatory data and case studies,and evaluated change management tools,providing recommendations for companies and regulatory agencies to manage CMC changes for CAR-T products.Regulatory analysis revealed that both China and the United States are at the forefront of policy development,with general principles based on science and risk.However,both regulatory agencies are still exploring and refining details and practices.Industry surveys indicated that one of the main purposes of CMC changes is to reduce costs and improve product accessibility,with major challenges including differences in understanding between companies and regulatory agencies,communication mechanisms,and approval timelines.The collected CMC change cases involves various scenarios,including capacity expansion.For such changes,it is recommended to use concurrent validation based on appropriate product and process knowledge,risk control,and sterile validation,with simulation validation as an auxiliary when necessary.For post-market change management tools,the study suggests piloting ICH Q12 Post-Approval Change Management Protocol(PACMP)to help manage post-market CMC changes for autologous CAR-T cell therapy products.
万方数据
维普
