Notification of “CAR-T Cell Quality Control Testing Research and Non-clinical Study Considerations”

Chimeric antigen receptor T cells (CAR-T) refer to the transfer of genetic material with specific antigen recognition domains and T cell activation signals into T cells through gene modification technology, so that T cells are activated by directly binding to specific antigens on the surface of tumor cells, directly killing tumor cells by releasing perforin, granzyme B, etc., and recruiting endogenous immune cells in the human body to kill tumor cells by releasing cytokines, thereby achieving the purpose of treating tumors. In addition, immune memory T cells can be formed to obtain a specific long-term anti-tumor mechanism. At present, CAR-T cells have shown very good clinical effects on a variety of blood tumors and have shown great potential for the treatment of solid tumors. In 2017, the United States approved the marketing of two CD19-CAR-T cell therapy products for acute B lymphocytic leukemia and B lymphocytic neoplasm, respectively. CAR-T cell therapy has become a new international research hotspot in the field of tumor immunotherapy. CAR-T research in my country is also booming. Many research institutions and pharmaceutical companies have invested in the research and development of CAR-T cell products. Many institutions have submitted clinical trial applications for CAR-T cell therapy products. The industrialization of CAR-T cell therapy has begun to take off in a variety of ways. At the same time, behind the upsurge of CAR-T cell therapy research, we must see that although CAR-T cell therapy has made encouraging progress, it is still an emerging field. On the one hand, there are still many problems to be solved in people's scientific understanding of CAR-T cell therapy. On the other hand, many new technologies are constantly entering this field, and people do not have enough data to evaluate its potential risks. In addition, cell therapy products have completely different characteristics from other non-in vivo expansion drugs, which are not only reflected in individualization, small production and limited batches, but also have problems such as large differences in starting materials, immature preparation processes, and complex biological efficacy and safety evaluation, which limit the rapid development of CAR-T cell therapy products. Therefore, how to improve the safety, effectiveness, quality controllability and product process consistency of CAR-T cell therapy products is a problem that every developer needs to face. This technical consideration point is aimed at the current status of domestic CAR-T cell product research and development, with the production process and product characteristics of CAR-T cell products as the main line, and the "Technical Guidelines for Research and Evaluation of Cell Therapy Products (Trial 2)" as the basic requirement. It puts forward guiding opinions on how to carry out quality control testing research and non-clinical evaluation of CAR-T cell products, and provides technical references for CAR-T cell product developers, so that my country's CAR-T cell product field can carry out research in accordance with certain specifications from the beginning, laying a good foundation for future industrialization. At the same time, the key points of this technology will be continuously revised as the research on various aspects of CAR-T cell products continues to mature, so as to gradually establish more scientific and reasonable requirements and standards for quality control testing and non-clinical evaluation of CAR-T cell products.

Specific news link: Notice on the release of "Key Points for Consideration in Quality Control Testing and Non-clinical Research of CAR-T Cell Therapy Products"