Bridging modelling and regulatory practice in CAR-T cell therapy development

CAR-T therapies present particular challenges for clinical development. Their manufacturing processes are complex and individually tailored, while eligible patient populations are often small and conventional clinical trial designs may not be well suited to these therapies. These characteristics create a need for alternative ways of generating and integrating evidence throughout development.

“Modeling and Simulation in Development and Regulatory Approval of Chimeric Antigen Receptor T-Cell Therapies: An Analysis of European Medicines Agency Centralized Procedures From 2018 to 2024” addressed this need by examining how modelling and simulation have been used in the development and regulatory approval of CAR-T therapies in Europe. Published in CPT: Pharmacometrics & Systems Pharmacology, the publication reviews regulatory procedures for six authorised CAR-T products and examines the role of modelling across pharmacokinetic, efficacy, safety, and benefit-risk questions.

A structured credibility framework was used to assess the modelling approaches and compare their application in regulatory submissions with established analytical methods. By organising regulatory questions and the methods used to address them into a structured repository, the study provides a basis for improving consistency and transparency in the assessment of model-based evidence.

In their analysis of the six CAR-T products, the authors found that modelling was applied to 26.4% of the 164 regulatory questions considered at initial authorisation. Pharmacokinetics accounted for the largest share of these applications, while modelling was used less frequently to address efficacy and safety. By comparing the regulatory submissions with the scientific literature, the study also identified differences in methodological maturity, with models used in regulatory settings generally being less mechanistically detailed.

ERAMET promotes the responsible uptake of reliable and transparent modelling tools to support more efficient and scientifically robust development processes. For ERAMET, the analysis offers valuable insights into the challenges and opportunities associated with applying innovative methodologies to complex and individualised therapies. By examining how modelling is currently used in regulatory practice, the study helps identify areas where greater consistency, transparency, and methodological development could support a broader use of model-informed approaches.

Discover the full analysis here!