Center for Drug Evaluation (CDE) Issued the Notification of “Technical Guideline for the Clinical Risk Management Plan for Marketing Application of Chimeric Antigen Receptor T cell (CAR-T) Therapy Pro

Chimeric antigen receptor CAR-T cells (CAR-T) refer to a type of T cell that can recognize a specific antigen by introducing vectors such as viruses into autologous or allogeneic T cells through gene modification technology, thereby expressing a chimeric antigen receptor (CAR) composed of an antigen recognition domain, a hinge region, a transmembrane region, and a co-stimulatory signal activation region. After CAR-T is infused into the patient's body, it can bind to specific antigens on the surface of tumor cells and activate them, and directly kill tumor cells by releasing perforins, granzymes, etc. to achieve the purpose of treating tumors. CAR-T has shown good clinical effects on a variety of blood and lymphatic system tumors, and has also shown great therapeutic potential for the treatment of solid tumors. At present, many products have been approved for marketing in the United States, the European Union, and China, and their indications include relapsed/refractory acute B-cell leukemia and B-cell lymphoma and multiple myeloma. Due to the characteristics and mechanism of action of CAR-T cell therapy products, adverse reactions such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been exposed during clinical trials. There are also other treatment-related operations such as lymphocyte removal pretreatment, which may cause hematopoiesis and infection. If appropriate treatment measures are not taken in time, serious consequences may occur. In addition to autologous CAR-T cells, transplant donor-derived CAR-T cells and universal CAR-T cells have also entered the clinical trial stage. Due to their novelty, complexity and technical specificity, they may bring long-term and potential safety risks to patients.

In order to promote early detection of such risks and provide effective risk control measures, this guideline, based on the ICH E2E pharmacovigilance plan, the Good Practice for Pharmacovigilance, and relevant guidelines for risk management plans at home and abroad, lists the possible safety risks of CAR-T cell therapy products, as well as the conventional and product-specific additional pharmacovigilance activities and risk minimization measures. Risk identification of CAR-T cell therapy products should start as early as possible and continue throughout the research and development process to prevent or minimize risks when possible. The risk management plan should be updated in a timely manner as the risk perception changes. This guideline includes the structure and content of the clinical risk management plan for CAR-T cell therapy products for marketing application, focusing on the special considerations for writing the risk management plan for CAR-T cell therapy products. The clinical risk management plan for CAR-T cell therapy products for marketing application should also refer to ICH E2E, the Good Practice for Pharmacovigilance, and relevant technical guidelines issued by my country's drug regulatory authorities. As technology develops and relevant research data accumulates, these guidelines will be updated in a timely manner.

Specific news link: Technical Guidelines for Clinical Risk Management Plans for Chimeric Antigen Receptor T-cell (CAR-T) Therapeutic Products