Recommendations on the report of the European Commission Scientific Conference ‘Non-Animal Approache
The European Commission published in April 2017 the report of the conference ‘Non-Animal Approaches – The way forward’ that they organised in Brussels on 6 and 7 December 2016. The Conference’s presentations and video recordings can be viewed on DG Environment website.
The conference was announced in the Commission’s response to the Europeans Citizens Initiative ‘Stop Vivisection’ as one of four actions that should contribute towards the goal of, ultimately, phasing out animal testing.
The key recommendations outlined in the report are extracted here for simplicity:
Recommendations Session 1 – Animal Testing Today
There is a need for on-going investment in public and private funding in non-animal alternatives. However, consideration is required to ensure the proposed research is appropriate, addresses areas of need, and is of high quality with appropriate statistical design. To achieve these goals, the following are required:
1. A thorough gap analysis of where alternatives are still lacking and how to improve the current alternatives to be fit for purpose
2. The investigation of more “human” testing e.g. using human cell-based systems
3. Consideration of whether there should be a more stringent scientific peer review of methodology before starting any project using animals or developing alternatives
4. A need for systematic use of ARRIVE, and other relevant guidelines to stimulate a culture of scientific excellence.
5. Improvements in study design and data analysis for all animal experimentation as well as for non-animal studies.
6. More standardisation, e.g. in design, analyses, statistics and publication
7. The need to publish negative results systematically – start with all publicly funded studies using animals
Recommendations Session 2 – Biomedical Research: Strengths and Limitations of Non-Animal Alternatives
1. There is a need for a continued and organised research agenda within Europe to co-ordinate the short-term and longer-term uptake of alternatives based around in silico and in vitro approaches in the short term and human-on-chip and microphysiological approaches in the longer term. Some more strategic top-down or central steering of this research agenda might be beneficial.
2. Fundamental biological research, from sequencing of human genomes to tissue and organ level biology, should not be discontinued as this will support the better development of the next generation of alternatives to animal testing.
3. Effort is required to speed up and possibly simplify the process of validation (also covered in a later session) leading to acceptance of alternatives and therefore greater uptake.
4. Greater resources should be made available for data sharing, including consideration of greater access to confidential data – or knowledge being made available from it. Resources such as patient DNA databases should be created for research purposes.
5. Education and training of all researchers using animals is mandatory in the EU, enforcement of compliance is necessary to ensure respect for animals and their correct, ethical use.
Recommendations Session 3 – Regulatory Testing: Strengths and Limitations of Non-Animal Alternatives
1. New approaches for the validation of complex alternatives need to be developed now, i.e. moving away from the one-to-one replacement paradigm, to ensure acceptance and uptake.
2. Regulators should lead the way whilst working closely with industry and other stakeholders.
3. The process should start with a common problem definition.
4. Work is required on defining, understanding and agreement on acceptable risk to human safety on using non-animal data – as a result regulation may need to be adapted.
5. Progress in the area of acceptance of alternatives must be collaborative at a number of levels and will require resources to achieve this:
a. International collaboration e.g. EU, US, Japan etc.
b. Stakeholders e.g. regulators, industry, developers etc.
6. Dates and targets for the phasing out of animal tests, where possible, should be considered. Although not all panellists considered that helpful.
7. Additional barriers to the acceptance of alternatives, beyond those already known, should be identified and strategies to remove them be defined.
8. There should be support for internationally led case studies to evaluate and demonstrate the acceptance of new alternative approaches. In this context, it could be helpful to carefully map out uncertainties of current animals tests.
9. An in vitro Mode of Action-based classification system like today’s GHS will be required.
Recommendations Session 4 – Reporting on European Commission Actions 1 – 3
1. The European Commission should continue its role to monitor compliance with Directive 2010/63/EU and to increase the vision of using alternatives to animals wherever possible.
2. Consideration could be given as to how the Three Rs could further be promoted through Directive 2010/63/EU e.g. through the use of dedicated information officers.
3. Access to knowledge sources should be reviewed and improved, for instance by their quality assurance and the provision of an (internet) one-stop-shop to access all resources using an improved search engine.
4. Support should be provided for dissemination events, such as conferences and workshops, to increase outreach especially for non-scientists.
5. Consideration should be given to require publication of Three Rs methods where possible.
6. Assistance should be provided to compile and publish negative data where possible, interoperable databases of information are one approach that should be investigated.
7. A funding strategy to promote knowledge sources for the Three Rs and access to them should be developed, including commitments from the European Commission and private industry.
Recommendations Session 5 – Responsible Research
1. The European Commission should continue (and increase) funding of research in alternatives in specific areas that will stimulate their uptake and implementation.
2. All EU agencies such as ECHA, EMA and EFSA and initiatives such as EPAA and IMI should further encourage the uptake of alternatives and the implementation of the Three Rs principles.
3. Science must make efforts to understand and remove all elements of bias from the experimental design and reporting of results.
4. The use of tools such as the NC3Rs Experimental Design Assistant should be mandatory in the design of experiments and be required by grants funding agencies.
5. The implementation of the NC3Rs ARRIVE guidelines should be mandatory in grant proposals as well as publication of results, starting with all publicly funded research using animals.
6. Greater efforts should be made to ensure results are openly available e.g. using data repositories such as European Open Science Could, allowing access to all results including negative results, and enabling free and easy data reuse; especially results derived from publicly funded research using animals.
7. Journal editorial policies should more fully embrace the Three Rs principles ensuring the ARRIVE guidelines have been respected.
8. The peer-review process should be assessed as to whether it is fit for purpose with regard to transparency and implementation / review of the Three Rs.
9. The assessment of research impact should be revised to remove the emphasis from highly significant “headline” results to ensuring quality and relevance.
10. 2020 should be designated the “Year of Systematic Review”.
11. Each Member State should be encouraged to have a Science Media Centre, such as that in the UK, which helps the general press with the correct reporting of research outcomes.
Recommendations Session 6 – The Future: The Way Forward
1. Harmonisation of all new methodologies is required; there is good progress for metabolomics as one example which should be supported.
2. There is a need for a large-scale evaluation of metabolomics to demonstrate its utility to identify mechanisms of action relating to chemical safety for a number of species.
3. Support is required to complete the development of technologies such “human-on-a-chip”, in readiness for industry adoption and validation.
4. There is a need to widen the Adverse Outcomes Pathway type approach to areas outside regulatory toxicity e.g. in disease modelling.
5. Human tissue should be made more readily available and this should be addressed at EU level.
6. All new technologies require some form of validation to demonstrate their fitness of purpose. Further efforts in developing validation schemes and strategies may be required.
7. iPS and related technologies should be developed to address specific organ level effects and disease treatments.
8. Further understanding of the limitations of the new technologies is necessary, especially how to scale up cellular based techniques to in vivo.
9. Patient groups should be informed about the new technologies, their advantages and risks.
10. Efforts to show how to combine all new technologies e.g. for drug safety are required which may need a new way of thinking both about the technology itself and the means of combining information.
11. There is a continued need for education and training in all aspects of animal-free science and the Three Rs; this is required at all levels from school and university students to established researchers in academic, industrial and contract laboratories. Proper and full dissemination of knowledge will be key to this. This will require the promotion of the new techniques and approaches and raising awareness of resources through well-designed internet resources and, preferably, a single search engine from which all information can be accessed. There is also a need to inform and educate the public more effectively including through Scientific Conferences and to maintain an open and constructive dialogue between stakeholders.