Before a new batch of medicines can be released for use, manufacturers must run certain tests to check that the batch is safe for patients, whether human or animal. The tests required to assess the safety and quality of different types of medicines are set out in a reference work called the European Pharmacopoeia. In the case of medicines administered by injection, such as vaccines, some antibiotics, and blood products, manufacturers have to test for pyrogens, contaminants which can trigger a fever. For decades, the rabbit pyrogen test (RPT) has been the most common pyrogen test, and today some 400 000 rabbits worldwide are subjected to the test every year.
IMI project VAC2VAC was launched with the goal of developing and validating non-animal testing approaches for both human and veterinary vaccines. One focus of the project was the monocyte activation test (MAT), a cell-based assay for pyrogens. The project validated the MAT for testing batches of ENCEPUR, a vaccine against tick-borne encephalitis virus (TBEV) and it was approved by the competent authorities in Germany, allowing the vaccine manufacturer, GSK, to start implementing the method.
‘A major achievement for animal welfare’
Now, VAC2VAC’s work has helped to convince the European Pharmacopoeia Commission (EPC) to eliminate the RPT from its monographs entirely. During a meeting in June 2024, the group deleted the RPT from 57 texts and added a new general chapter on pyrogens. The new rules will come into force on 1 July 2025. After that, the RPT will no longer be required and medicines developers will be able to select a suitable in vitro test, such as the MAT, to test their products for pyrogens.
The European Directorate for the Quality of Medicine and HealthCare (EDQM) is the directorate of the Council of Europe responsible for the European Pharmacopoeia. In a statement, they hailed the news as ‘a major achievement for animal welfare’, adding: ‘The EPC is committed to the reduction of animal usage wherever possible in pharmacopoeial testing. This historic step is an illustration of this commitment and will have a significant impact on the replacement, reduction and refinement of animal tests in the quality control of medicines.’
Collaboration is key to success
Meanwhile, the European Vaccine Initiative (EVI), which coordinated VAC2VAC, noted that the collaboration between academic partners, industry and regulatory agencies was key to the success of the project.
‘In 2015, at the start of VAC2VAC, almost 50 000 rabbits were used for pyrogen testing in 14 Member States of the European Union,’ the EVI writes in a statement. ‘The discontinuation of the rabbit pyrogen test underscores the importance and concrete results of collaborative research when validating and introducing new approaches in pharmaceutical research.’
VAC2VAC was supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.