As a Programme Manager in Toxicology and Regulatory Sciences at the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), it was fantastic to see another session championing the 3Rs. I was particularly pleased to see our ARRIVE guidelines referred to, which aim to improve the reporting of research using animals.
The Symposium Session “Scientific and Regulatory Update in the Application of the 3Rs Principle in Chemical and Drug Development” at the SOT 58th Annual Meeting and ToxExpo was a very varied session, showcasing examples from different regions and sectors where efforts are being made to minimize animal testing. Dr. Wally Hayes chaired the session, with Dr. Brinda Mahadevan acting as co-chair and giving the opening talk. Brinda focused on the topic of testing requirements for generic pharmaceuticals and advocated case-by-case rather than default strategies—for example, depending on changes in intended use, formulation, or dosing (e.g., oral solution versus capsules, lotion/foam versus cream). She talked about initially using literature data or in silico or in vitro tests to inform and minimize any subsequent animal testing. She discussed “savvy” study designs, which do not compromise the experimental intent (e.g., reduced numbers of dose groups and no recovery groups).
The second speaker, Dr. Anna Lowit, switched gears to offer a regulatory perspective on testing requirements for pesticides. Compared to other sectors, pesticides have the largest use of animals for regulatory purposes. Much of this is due to acute toxicity “six pack” studies, which are associated with high levels of animal suffering, and there are also questions around their value and use in decision-making. Anna talked about desire of the US Environmental Protection Agency (US EPA) to rethink pesticide testing requirements to “reduce the animal footprint” and increase human relevance. The US EPA are committed to exploring opportunities to use nonanimal methods to modernize these tests, and their efforts in the areas of eye and skin irritation, skin sensitization, and acute dermal toxicity were presented. Anna showed how multiple nonanimal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrate comparable or superior performance to the mouse local lymph node assay (LLNA). However, it was highlighted that we need to take a step back and to rethink how we do things—always benchmarking against existing animal tests that have their own limitations and drawbacks does not make sense. We need to work toward better and more predictive solutions.
The final presenter, Dr. Marcel Leist, highlighted the work of EU-ToxRisk, which is a European collaborative project funded by the EU Framework Programme for Research and Innovation, of which the NC3Rs are a consortium partner. He talked about using new approach methodologies (NAMs) guided by adverse outcome pathways (AOPs) to support read-across and thus make predictions on the toxicity of chemicals where data are lacking by linking them to related compounds where there is existing information. Marcel emphasized the importance of problem formulation and how read-across (perhaps in conjunction with other nonanimal data) can be used to answer specific questions.
This Symposium clearly demonstrates that implementing the 3Rs not only reduces the use of animals but also can act as a driver for more predictive scientific tools to be developed. However, global harmonization remains a key challenge. Since most companies aim for worldwide marketing of their products, a lack of harmonization of regulatory requirements can lead to some studies being carried out in animals to meet the requirements of a single region, thus expanding the overall data package. Therefore, it will be important to ensure progress in this area occurs at a global level, so that regulatory changes are implemented as widely as possible, to fully realize the scientific and 3Rs benefits. It will be exciting to see how this develops.
This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.