imSAVAR: Human-Based Testing Strategies for Improved Drug Safety

The European research project imSAVAR (Immune Safety Avatar) has been successfully completed. The aim of the project was to develop innovative, human-relevant testing strategies to predict immune-mediated adverse effects of modern biopharmaceuticals and thereby fundamentally improve preclinical safety assessment. A particular focus was placed on severe immune reactions such as cytokine release syndrome (CRS) as well as immune-mediated skin reactions, which represent major challenges in the clinical development and use of biotechnological drugs.

Within imSAVAR, the researchers pursued an integrated approach combining human-based in-vitro models, functional immune assays, multi-omics analyses, and computational modeling. These data were systematically translated into adverse outcome pathways (AOPs) and AOP networks to map mechanistic links between molecular initiating events and clinically relevant endpoints. A special emphasis was placed on the derivation of quantitative predictive markers that enable early risk assessment and are suitable for regulatory use.

Researchers at Fraunhofer ITEM contributed their recognized expertise in the development and application of human-based, immunocompetent test systems as well as in translational immunotoxicology to the consortium. The project outcomes make an important contribution to Next Generation Risk Assessment (NGRA) and to the international acceptance of new approach methodologies (NAMs) as alternatives to animal testing. Overall, the results of imSAVAR strengthen Europe’s position in the field of innovative safety assessment and provide a robust foundation for future regulatory and industrial applications.