Research on the development of alternatives to animal testing for pharmaceutical products and international standardisation

Scientists are working to develop new and innovative alternatives to animal testing that don't rely on the use of animals. Takao Ashikaga, Hajime Kojima and Yoko Hirabayashi are part of JaCVAM which works to promote the use of alternatives to animal testing. The goal is to replace, reduce or refine (3Rs) the use of animal under International harmonization. Hirabayashi is also the representative of a research group that is funded by the AMED and the representative of a research group funded by the MHLW. A challenge the researchers are facing in their quest to ensure the welfare of experimental animals and also ensure the safety of various pharmaceutical and chemicals is the lack of biomarkers to more accurately predict toxicity for regulatory acceptance. This means that without animal testing more costly and complex non-animal methods are required and presents a barrier to the adoption of non-animal methods for international standerisation. As such, there is a need to develop an easy way to obtain a lot of information. Hirabayashi and the team are working on the development of AI that can be used to evaluate the safety of different compounds. The researchers are developing in vitro assays such as ordinary 2-dimensional culture, 3-dimensional culture including organoids or spheroids, reporter gene assay and organ-on-a chip; and in silico assays such as computer toxicology using QSAR and Read Across. The researchers hope that their innovative work will contribute to the 3Rs, benefiting animal welfare for regulatory use.

Curated Data In — Trustworthy In Silico Models Out: The Impact of Data Quality on the Reliability of Artificial Intelligence Models as Alternatives to Animal Testing

New Approach Methodologies (NAMs) that employ artificial intelligence (AI) for predicting adverse effects of chemicals have generated optimistic expectations as alternatives to animal testing. However, the major underappreciated challenge in developing robust and predictive AI models is the impact of the quality of the input data on the model accuracy. Indeed, poor data reproducibility and quality have been frequently cited as factors contributing to the crisis in biomedical research, as well as similar shortcomings in the fields of toxicology and chemistry. In this article, we review the most recent efforts to improve confidence in the robustness of toxicological data and investigate the impact that data curation has on the confidence in model predictions. We also present two case studies demonstrating the effect of data curation on the performance of AI models for predicting skin sensitisation and skin irritation. We show that, whereas models generated with uncurated data had a 7–24% higher correct classification rate (CCR), the perceived performance was, in fact, inflated owing to the high number of duplicates in the training set. We assert that data curation is a critical step in building computational models, to help ensure that reliable predictions of chemical toxicity are achieved through use of the models.

Swiss 3R Competence Centre: Promoting the 3Rs implementation

This contribution describes the history and activity of the Swiss 3R Competence Centre (3RCC), which has been founded in 2018. Among the most relevant activities, a call for project proposals on 3Rs was launched in 2018, with 47 proposals received for selection, followed by a call for nominations for a 3Rs award, which will be announced in Sept. 2019. Implementation of a 3Rs educational program has also been carried out since 2018. The 3RCC is also developing an e-Learning module to promote the implementation of alternatives to animal testing. Finally, the centre activity is addressed to help fostering good experimental design and biostatistics practices and support.

Characterising the current provision of education and training courses relevant to the Replacement, Reduction and Refinement (Three Rs) of animals used for scientific purposes

A recent study by the Joint Research Centre (JRC) of the European Commission showed that although much knowledge exists on the Three Rs (Replacement, Reduction and Refinement of animal procedures), there is a clear need for better education, communication and outreach to enhance knowledge sharing and promote their uptake. The JRC is now completing an extensive overview of the Three Rs education and training landscape by mapping currently available courses and resources worldwide. In addition, it has launched a project to investigate the feasibility of including the Three Rs in educational curricula under a European Parliament Pilot Project, which aims to promote alternatives to animal testing.