Carlota Saorsa / HIDDEN / We Animals

22 September 2024

The European Pharmacopoeia Commission took a historic step by removing the rabbit pyrogen test from the European Pharmacopoeia in favour of the use of non-animal methods. This decision will not only spare the lives of tens of thousands of rabbits in the EU every year, but will also better ensure the safety of medicines and vaccines.

This long-debated method, which raised ethical concerns and had limitations in accuracy and reproducibility, now belongs to the past. 

Pyrogens are fever-inducing substances that can unintentionally contaminate injectable medicines, and their detection is crucial to ensure the safety of these products.

Developed in the early 1900’s, the rabbit pyrogen test was the predominant method for detecting pyrogens. It involves injecting the test substance intravenously into a vein of the rabbits’ ears and observing their reaction, mainly an increase in body temperature. These injections can be repeated until their ears are severely damaged and can no longer be used, or until they show a reaction. In all cases, rabbits are killed at the end.

The limitations of the rabbit pyrogen test are widely recognized, including limited sensitivity and reproducibility. Repeated injections can lead to the development of pyrogen tolerance, while the inherent stress of the test can also affect results.

Alternative non-animal methods with improved sensitivity and relevance have been available for more than 20 years.

Despite many years of efforts to promote the use of non-animal methods for both ethical and scientific reasons, the rabbit pyrogen test remained the standard for detecting pyrogens, resulting in the suffering and death of approximately 25,000 rabbits annually in the EU.

In June 2024, the European Pharmacopoeia Commission, a regulatory body responsible for overseeing the safety of medicines, adopted 57 revised texts in the European Pharmacopoeia. Drug developers will now be required to choose non-animal methods for assessing the pyrogenicity of their products. Among the available methods, the Monocyte Activation Test (MAT) has emerged as a highly reliable and accurate solution for pyrogen detection. This test is based on the response of human immune cells to pyrogens, offering greater sensitivity and reproducibility than the rabbit assay.

This decision marks a significant milestone in the transition away from animal-based testing methods. It is hoped that it will pave the way for the adoption of more innovative and reliable non-animal approaches across various scientific fields.

Regards Mark