Novelties by EMA on medicinal products with genetically modified cells

Updated EMA guideline for medicinal products containing genetically modified cells provides innovations, recommendations and improvements to be implemented

An actual problem in cancer therapy is the limit of treatment options for tumors that are “invisible” to the immune system. This is where CAR T cell immunotherapy comes in, with outstanding therapeutic success in advanced tumor diseases. The patient's own T cells are isolated and genetically modified so that they form a chimeric antigen receptor (CAR) on their surface. With this CAR construct, tumor cells can be recognized and ultimately destroyed.

The acquired growth in knowledge and experience in genetic engineering (especially genome editing) and the clinical application of CAR T cells is regularly incorporated into guidelines. In June 2021, an updated version of the EMA Guideline “Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells” will come into force. This contains recommendations on the development, evaluation and marketing authorization submission of medicinal products containing genetically modified cells for human use. Moreover, it considers starting materials, comparability and validation, including implications for reagents/tools.

Appendix I of the guideline lists special considerations for CAR T cells and points to improving data on efficacy and safety. Furthermore, pharmacokinetics/dynamics and dose finding are addressed. Additionally, recommendations are provided for evaluating cell kinetics and appropriate methods for quantification of CAR T cells. The same basic principles regarding efficacy apply to CAR T cells in the hemato-oncology setting as to other anticancer medicinal products, whose clinical endpoints for measuring the effects of CAR T cell therapies are also considered. Due to pharmacokinetic/dynamic properties of CAR T cells and acute toxicity, safety for data generation needs to be addressed intensively.

Author: Dr. Mario Ramos Tirado, Valicare GmbH