FDA Guidance for Chimeric Antigen Receptor (CAR) T Cell Products

In the recent past, there has been a significant increase in research and industry efforts in the field of human gene therapies. In particular the field of Chimeric Antigen Receptor (CAR) T cell products has become increasingly important for the recognition of a target antigen for therapeutic purposes.

This development is also taken into account by the authorities. Thus, corresponding guidelines are published to provide industrial and university institutions with guidelines and recommendations for development, approval and production.


In March, the US FDA has published a draft guidance document entitled "Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products". This document contains CAR T cell-specific recommendations on chemistry, manufacturing and control (CMC), pharmacology and toxicology, and clinical trial design. The recommendations relate to autologous or allogeneic CAR T cell products. In addition, the guidance also provides guidance on analytical comparability studies for CAR T cell products.

Although the guidance focuses on CAR T cell products, the FDA considers many of the recommendations made to be applicable to other gene therapy lymphocyte products such as CAR natural killer (NK) cells or T cell receptor (TCR) modified T cells.  However, the FDA emphasises that these highly specialised products often require considerations beyond this guidance.

The FDA explains in its document that they are well aware of the challenges in the development, manufacture, testing and clinical evaluation of CAR T cells, e.g. in the design and appropriate testing of the CAR transgene and the delivery vector, both of which are critical to product safety, specificity and function.

The FDA recognises that "CAR T cell manufacturing involves multiple biological materials and complex multi-step procedures, which are potential sources of variability among product lots." This fact makes it imperative to give detailed consideration to appropriate manufacturing process controls and in-process and batch release testing, as these are necessary to ensure CAR-T cell safety and quality, as well as consistency between batches.


The guideline also goes into further detail and addresses the following topics:

  • General considerations for CAR T Cell Design and Development 
  • CMC Recommendations 
  • Preclinical Recommendations 
  • Clinical Recommendations 
  • Clinical Pharmacology Recommendations 
  • Safety Evaluation and Monitoring 
  • Persistence of CAR T Cells and Long Term Follow-up 
  • Allogeneic CAR T cells

For further details, please refer directly to the draft guidance "Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products".

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