The future of pyrogenicity testing: Phasing out the rabbit pyrogen test. A meeting report

Abstract

The rabbit pyrogen test (RPT) was the benchmark for pyrogenicity testing, but scientific advancements have provided innovative and humane methods, such as the in vitro monocyte-activation test (MAT). However, transitioning from the RPT to the MAT has been challenging. The European Directorate for the Quality of Medicines & HealthCare, the Council of Europe, and the European Partnership for Alternative Approaches to Animal Testing jointly hosted an international conference entitled "The future of pyrogenicity testing: phasing out the rabbit pyrogen test". The conference aimed to show how the European Pharmacopoeia intends to remove the RPT from its texts by 2026, facilitate the use of MAT, and identify gaps in the suppression of RPT. The events contributed to a better understanding of the barriers to RPT replacement and acceptance of in vitro alternatives. Participants comprised stakeholders from Asia, Europe, and North America, including vaccine developers, contract laboratories, and regulators. Participants shared their replacement strategies and experiences with MAT implementation. They emphasised the need for continued cooperation between stakeholders and stressed the importance of international harmonisation of regulatory requirements to help accelerate MAT acceptance outside Europe. Despite the challenges, the willingness to eliminate the unnecessary use of RPT was common across all participants.