Rabbit pyrogen test has been deleted from EU medicines rulebook
Cell-based methods can now completely replace the cruel rabbit test in the EU and UK
The rabbit pyrogen test has finally been removed from regulatory standards set for medicines in the European Union and UK – and progress is being made towards making the test obsolete worldwide.
The cruel test, which is used to determine if medicines have been accidentally contaminated by checking for signs of a fever in the rabbit, has been removed from the EU’s ‘rulebook’ for medicines safety, the European Pharmacopoeia, as of 1 January 2026. The EU had promised to end the pyrogen test within five years in 2021.
Late last year, the World Health Organisation (WHO) also published new guidance on the replacement of animal tests for the quality control of biological products, such as vaccines. The guidance includes a dedicated chapter on pyrogen testing, highlighting that the available non-animal methods are superior to the rabbit test. This is instrumental in a global shift away from the use of rabbits, in alignment with that seen in Europe.
During the animal test, rabbits are restrained in boxes and have temperature probes inserted deep into their rectums for hours at a time, whilst the substance is injected into a vein in their ear. Rabbits typically undergo repeated injections until their ears become too damaged to be used again, or they experience a reaction – in which case they are killed.
In the EU and UK, the animal test can now be fully replaced with cell-based methods such as the monocyte activation test (MAT), which use human white blood cells.
The rabbit pyrogen test is one of the animal experiments featured in our Replace Animal Tests (RAT) List, which we created over a decade ago to highlight tests which already have approved non-animal replacements. We are delighted that UK and European regulations, including the standards set within the Pharmacopoeia, are no longer a barrier to the full replacement of this animal test.
Changes to the European Pharmacopoeia also extend beyond the EU. The UK remains a member of the Council of Europe, the organisation which upholds democracy across the continent, meaning that the rabbit test will also be dropped from rules and regulations set out under UK law. This aligns with commitments made in the recently published UK strategy, Replacing animals in science: A strategy to support the development, validation and uptake of alternative methods, to end the rabbit pyrogen test by the end of 2025.
Our Director of Science and Regulatory Affairs, Dr Emma Grange, said: “This is hugely welcome and significant news with potential to have a global impact. The rabbit pyrogen test should have ended many years ago but now we hope that the rationale behind the ban can be extended to other out-dated tests which could be replaced tomorrow.”