The European Pharmacopoeia Commission removed the rabbit pyrogen test from 57 pharmacopoeial monographs during its 179th session in June 2024. This change is a milestone in the development of the European Pharmacopoeia in terms of the replacement, reduction, and refinement (RRR) of previously legally prescribed animal experiments in medicinal product testing.
Representatives from the Paul-Ehrlich-Institut (PEI), Federal Institute for Vaccines and Biomedicines, and the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) are members of the German delegation to the European Pharmacopoeia Commission.
The rabbit pyrogen test was first developed in the 1940s. The test involves measuring the increase in rabbits' body temperature after they have been injected intravenously with the test substance. Fever-causing substances known as pyrogens and endotoxins can be detected with this test. Since its creation, the rabbit pyrogen test has been an important test in medicinal product development for the early detection of impurities that could cause life-threatening side effects in patients. It took about 20 years to develop alternative methods and to be able to provide evidence of their equivalence to the animal model with substantial data.
The first alternative test was developed using blood from horseshoe crabs (limulus amoebocyte lysate test, LAL), an endangered animal species. Newer tests such as the recombinant factor C test for endotoxins and the monocyte activation test for pyrogen content can now completely dispense with animals or material of animal origin. A large number of initiatives were funded by the EU, the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG) and the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF). This support lead to a number of research projects being carried out at the Paul-Ehrlich-Institut.
The European Pharmacopoeia (Pharmacopoea Europaea, Ph. Eur.) is published in English by the European Directorate for the Quality of Medicines and HealthCare (EDQM) in Strasbourg. The pharmacopoeia contains established pharmaceutical rules for the quality, testing, storage, dispensing, and labelling of medicinal products and the substances used in their manufacture. It also contains rules for medicinal product containers and packaging. The marketing authorisation process includes compliance with the requirements of the pharmacopoeia and implementation of changes as needed.
The Pharmacopoeia Commission is responsible for all pharmacopoeia content and strives to ensure that all requirements, with a particular focus on technical requirements, are assessed with regard to their expediency before coordination activities take place. The commission meets three times a year. The content is coordinated in working groups made up of experts from regulatory authorities, such as the Paul-Ehrlich-Institut, and representatives from pharmaceutical companies. In addition to the EU countries, other countries are also involved as either members or observers.
Updated: 18.07.2024
