The need for non-human primates in biomedical research, production and testing of products and devices (update 2017)
Non-human primates are used in medical research because of their similarities to human beings. Results from research on non-human primates can often be applied to humans, and scientists have learned much about diseases, disorders, prevention and treatments for both humans and animals. Using animals that are so similar to humans, however, raises serious ethical concerns, which is why the use of non-human primates is monitored and strictly regulated. Animal testing for cosmetics was entirely banned in the European Union in March of 2013, and much also has been done to specifically safeguard non-human primates: non-human primates used for research, for example, can no longer be obtained from the wild unless the objectives of the study specifically requires the use of wild-caught; and the use of great apes has been prohibited. As long as non-human primates continue to be used for medical research, the European Commission strongly advocates the "3Rs principle", now a legal obligation embedded in the EU legislation to: Replace non-human primates with viable alternatives whenever feasible, Reduce the use of non-human primates and Refine scientific procedures and the care and treatment of the animals. This Opinion is an update of the 2009 Opinion and addresses issues specifically related to implementing the "3Rs principle".
- 1. Introduction
- 2. Background
- 3. Current use of non-human primates
- 4. Alternatives to the use of non-human primates
- 5. Reducing and refining the use of non-human primates
- 6. Determining a timeline for phasing out the use of non-human primates
- 7. Implications of an EU-ban on the use of non-human primates
- 8. Research areas to explore to further the 3R principle
- 9. Conclusion and Recommendations
9. Conclusion and Recommendations
9.1 SCHEER's conclusions
The use of non-human primates remains necessary for certain types of research, but when their use is required – to be determined on a case to case basis and only if no viable alternatives are available - it is essential to adopt the highest standards of non-human primates housing and husbandry and to follow best practice in the conduct and refinement of scientific procedures. 23 recommendations on implementing the 3Rs (Replacement, Reduction and Refinement) and on overcoming barriers to doing so are given in the Opinion.
Decisions about the need for non-human primates in research projects or regulatory testing should be made on a case-by-case basis, based on strong scientific rationale and the availability of alternative approaches.
To fully apply the 3Rs and maximise the benefits, there is a need to ensure that as new knowledge, technologies and approaches emerge there is timely assessment and evolution of research strategies, study designs, scientific procedures and husbandry, throughout the lifetime of research projects. Applying the 3Rs has both scientific and economic merit. Replacements may be more scientifically valid, and more cost effective. Reduction of animal numbers has clear economic benefit, and methodological/experimental. Refinements in procedures that do involve animals often produce more reliable and reproducible data.
If non-human primates are considered necessary for certain uses, it is essential to adopt the highest standards of non-human primates housing and husbandry and to follow best practice in the conduct and refinement of scientific procedures. In addition, experimental design, analysis and reporting are key means of maximising the knowledge gained from animal experiments and avoiding wastage of animals. Appropriate training for all those working with non-human primates is essential to ensure compliance with legislation, excellence in science, animal welfare and full implementation of the 3Rs.
A total of 23 recommendations are given in the Opinion, 18 of them concerning advancing the 3Rs and the remaining six suggesting ways to overcome barriers to achieving this aim. Some of the recommendations given in the Opinion regarding the 3Rs were already listed in the EU Directive 2010/63 as requirements, but were incorporated into the Committees series of recommendations in order to emphasise their importance in relation to the use of non-human primates and to encourage their full and rapid implementation in all member states. The recommendations can be read in full at the end of the Opinion .
9.2. SCHEER's recommendations in full
Some of the recommendations given below are already requirements of the Directive on animal protection and are being repeated here to emphasize their importance and to encourage their full and rapid implementation in all Member States.
Recommendations for advancing the "3Rs principle":
1. Decisions about the need for non-human primates in research projects or regulatory testing should be made case-by-case based on strong scientific rationale and the availability of alternative approaches.
2. In contrast to current areas of research with great potential to replace current non-human primate use such as in safety testing of pharmaceuticals, other areas of research, partly new, may require increased non-human primate use in the future, e.g., emerging infectious diseases. A solid harm-benefit assessment is needed here, too. The majority of non-human primate use in the European Union is for safety assessment studies, performed to meet regulatory requirements. Non-human primates should only be used when there are no alternatives and it is scientifically demonstrated that none of the other non-rodent species commonly used in safety testing is appropriate for the purpose of the study.
3. Progress has been made in identifying opportunities to avoid non-human primate use where they are not a relevant species or alternative species can be used, and in identifying efficient study designs using fewer animals where non-human primate use is scientifically justified. This progress has largely been led by the NC3Rs (UK National Centre for the Replacement, Refinement and Reduction of Animals in Research) working in collaboration with industry companies and regulatory bodies internationally, acting as a honest broker for pre-competitive data sharing and providing an open forum for dialogue between the parties. The evidence base and recommendations are being put into practice, but there is scope for wider uptake across the industry to further advance the 3Rs.
4. Research funders and ethics committees should ensure that research is conducted on non-human primates only where there is no suitable alternative approach, and where there is a high likelihood of producing scientific, medical or social benefit. This may require improvements to existing peer review processes to make them more robust. It is recommended that an international working group develops a clear listing of the elements that should be scrutinised by project evaluators for their authorisation and/or funding including experimental design and systematic inclusion of a publication plan (including for negative results) for non-regulatory projects. Researchers should report their non-human primate studies in compliance with the ARRIVE Guidelines (http://www.nc3rs.org.uk/ARRIVE) in order to maximise the information published and avoid unnecessary studies.
5. With regard to transgenic techniques in non-human primates, the SCHEER recommends that the European Commission form a working group to assess the scientific and ethical implications of such research to determine if it should be allowed in the European Union and, if so, within what constraints.
6. Conduct systematic reviews in all areas of non-human primate research, where possible, to conclude on its value, translational relevance and necessity in the context of alternative approaches. Cross-company and cross-sector data sharing would be a path forward for this type of retrospective assessment of non-human primate studies.
7. Where non-human primate research is necessary and justified, it should be performed to genuinely high standards of experimental design and technical practice, ethics and animal welfare. Experiments should be performed by appropriately trained and skilled staff with the necessary knowledge, resources and infrastructure to fully implement the 3Rs, as required by legislation and expected by general public. To this end, we recommend that consideration be given to focusing non-human primate research in centres of excellence and improving existing networks for information sharing.
8. Researchers, ethics committee members, animal welfare committee members and animal care staff must ensure that they keep abreast of the latest techniques that enable reduction in animal numbers and the refinement of methods and techniques to reduce suffering, and put this evidence base into practice. Ideally, this is a continuous process of improvement and CPD (Continuing Professional Development). Institutional constraints on implementation of the 3Rs should be recognised and addressed. Training should be included in non-animal methods to improve skills in multidisciplinary science and technology can help drive the development of non-animal technologies by training researchers in new skills for continuing their research in their field, without animal use.
9. CPD (Continuing Professional Development ) should be seen as an essential part of the training process for research workers using non-human primates. Researchers, veterinarians and animal technicians should make full use of the CPD opportunities available, and this should be supported by their research organisation. CPD should form part of training records and assessment of competency.
10. Available training opportunities are fragmented and not always aligned with best practice. Consideration should be given to development of an accredited, harmonised training course for those involved in non-human primate research to provide a solid foundation in non-human primate behaviour and best practice in their care and use.
11. Funding should also be provided for exchange visits and practical workshops for those directly involved in the care and use of non-human primates to facilitate sharing of best practice.
12. Whilst there has been progress with refinement of neuroscience studies involving non-human primates, funders and researchers should focus on significantly refining devices and methods as well as improving the spatial and temporal of existing and new non-invasive imaging technologies to refine, validate and ultimately replace the use of highly invasive techniques in non-human primates. Experiments should make full use of modern imaging, biotelemetry, virtual models and other technologies, and sharing of data and resources (animals, tissues and equipment) between researchers and institutions, to reduce and refine non-human primate use.
13. There needs to be improved means of assessing pain and distress in non-human primates, including the psychological impact of their use in research. Scientific knowledge about the welfare impact of husbandry and procedures, even after refinement measures have been applied, needs to be factored into harm-benefit assessments.
14. Reduction in non-human primate use would be assisted by greater use of more efficient experimental designs (e.g., factorial designs). Careful consideration should also be given to sample size calculations for non-human primate studies. The NC3Rs Experimental Design Assistant (https://eda.nc3rs.org.uk/) is one source of tailored advice for those lacking institutional access to expert statistical support.
15. Breeding facilities should contribute to improvements in both animal welfare and quality of science by ensuring that animals are well habituated to humans and better able to cope with scientific and husbandry procedures.
16. Literature searches, mainstream scientific and specialist conferences and resources from institutions like the NC3Rs (https://eda.nc3rs.org.uk/) are all sources of information and advice on opportunities to apply the 3Rs and the benefits of this. Researchers and associated animal care staff should ensure that they continually review and adapt their working practices accordingly.
17. For the sake of transparency and monitoring progress in the application of the 3Rs, it would be desirable that all Member States report on the level of severity of experimental procedures, origin of animals, generation and first time use.
Recommendations on how to overcome barriers:
18. To overcome the wider social, non-technological barriers to the implementation of alternatives it will be necessary to stimulate changes in both scientific and societal attitudes and in scientific practice by improving and expanding the 4Cs (Commitment, Communication, Cooperation and Coordination). This will influence the risk aversive nature of society that makes it difficult to move away from familiar methods to new alternative methods, where there is less historical data to fall back on. The 4Cs will also help to reduce problems related to competition, the reputation of researchers and entrenchment and policy create problems.
19. When communicating about non-human primate use with the public, the scientific community should provide an accurate description of the benefits, harms to animals and limitations of such research, and be realistic about the potential outputs and impacts. For safety testing, regulatory requirements and scientific consideration, it is possible to use non-human primates, with proof that non-human primates are most representative of humans, regarding pharmacodynamics and pharmacokinetics.
20. Researchers should report their experimental methods and results comprehensively, accurately and transparently. They should transparently evaluate and report on the progress in the development of alternative methods and their validation, but also on scientific limitations of alternative methods as well as the uncertainty of how to translate the findings from such models and build up the necessary knowledge base to refer to.
21. It is also necessary to reduce the timescale and bureaucracy associated with the process of formal validation and to overcome the lack of regulatory harmonisation both within and across sectors.
22. The European Commission should instigate strategic research funding initiatives to support the scientific and technological development required to achieve non-human primates replacement, or at least considerable progress towards it. This would also help the scientific community meet the policy objectives of the Commission.
23. To progress towards complete replacement of non-human primates in safety testing, it will be necessary to gain advance molecular biology techniques, including, for example, a better understanding of signalling pathways, mode-of-action information, modelling and bioinformatics. By integrating these data and the results of in vitro testing, —omics technologies applied to in vitro systems and physiologically-based pharmacokinetic modelling, non-animal models will together more closely represent what happens in a human body.