Our WP3 project leaders Dr. Katherina Sewald and Prof. Dr. Armin Braun from Fraunhofer ITEM joined our project partners at the Paul-Ehrlich-Institut for a talk on “Immune-related Adverse Outcome Pathways in regulatory decision making” on March 21, 2024.
imSAVAR aims to develop a systematic and holistic framework for the preclinical safety assessment of biotherapeutics and cellular therapies. The consortium focuses on immunoregulatory therapeutics, one of the world’s most important drug classes.
Within imSAVAR, we are introducing the concept of irAOPs to improve the preclinical safety assessment of biotherapeutics and cellular therapies. AOPs offer a mechanistic representation of critical undesired effects and have been established as versatile tools in toxicology and risk assessment for over a decade.
What are irAOPs?
The AOP framework is a way to organize information about each step in a toxicity pathway from an initial event to an adverse outcome. It is somewhat like identifying the first and last domino in a chain reaction – and all the dominoes in between – and indicating which key events along the way cause each domino to fall. This pathway approach shows how an adverse outcome occurs, not just that it happens.
Why are irAOPs important?
· Mechanistic description of the adverse effects
· Development of novel, human-based, immunocompetent models
· Setting up of AOP-informed, multistage testing strategies
The AOP concept provides additional guidance on systematically conducted preclinical safety assessments. It helps to identify relevant test systems and essential experiments to demonstrate the safety of new immune-relevant therapeutic agents.
The audience included a cross-section of the Paul-Ehrlich-Institut’s employees, ranging from basic researchers such as graduate students and postdocs to assessors in the field of monoclonal antibodies and ATMPs, as well as the Vice President and President of the Institute.
A big thank you to the Paul-Ehrlich-Institut for the opportunity to present and discuss these important topics.
About the Paul-Ehrlich-Institut: The Federal Institute for Vaccines and Biomedicines is a senior federal authority reporting to the German Federal Ministry of Health. It is responsible for the research, assessment, and marketing authorization of biomedicines for human use and immunological veterinary medicinal products. Its remit also includes the authorization of clinical trials and pharmacovigilance. The Institute’s research areas include allergology, bacteriology, biotechnology, immunology, hematology, transfusion medicine, veterinary medicine, and virology.