Supporting 3Rs approaches in biologicals testing

Up to 10 million animals a year are used worldwide in the development, production and quality control of biologicals such as vaccines (e.g. diphtheria, tetanus and polio), immunoglobulins (e.g. snake antivenoms), blood products and hormones. More than two-thirds of these animals are used for routine quality control batch release tests of licensed products. These tests are expensive, can cause significant pain and distress to the animals and have a high degree of variability which may cause lengthy delays of up to a year to the release of some biologicals and vaccines. 

With previous Bill & Melinda Gates Foundation funding we have reviewed the animal testing requirements in World Health Organisation (WHO) guidelines for the quality control and batch release testing of vaccines and biological therapeutics. This follow-on project funded by the Gates Foundation will support delivery of the 3Rs impacts of our recommendations, driving their implementation and accelerating the adoption of the latest non-animal testing methods by the global biologics community. Embracing the latest advances in replacement technologies will support faster access to cheaper vaccines by the communities who need them most urgently. 

We aim to drive the global adoption of non-animal testing strategies in order to optimise quality control testing of biological products by:

• Supporting the WHO in implementing the recommendations from our review.

• Facilitating the uptake of existing non-animal technologies for batch release testing by global biologics manufacturers and regulators.

• Supporting the development of new 3Rs approaches for batch release testing where they are needed most urgently, for example in assessing potency and neurovirulence.

• Building an evidence base for the removal of obsolete animal tests.

We have run two stakeholder surveys to gain insights from the global biologics community to help shape our work driving the wider adoption of non-animal approaches in biologics quality control testing. 

The first was for individuals who work for manufacturers, Contract Research Organisations, National Regulatory Authorities and National Control Laboratories. The aim of this survey was to assess awareness, adoption, barriers and opportunities related to implementing 3Rs approaches in global biologics quality control testing. The data from this survey has now been published. The results highlight support for non-animal methods with most respondents already actively implementing alternatives. Responses also emphasised the important role the WHO and regulators play in ensuring mature alternatives are available and encouraged for adoption – including cases where adoption has been slow due to cost, a lack of training and regulatory harmonisation.

The second survey focused on the use of the monocyte activation test (MAT) as a replacement for the rabbit pyrogen test to better understand current practices and opportunities to increase uptake, including how the test is validated, the cell types involved and barriers to implementation. Results will be published in due course.