Non-human primates in research and safety testing

7. Conclusions and recommendations

The SCHER opinion states:

3.1.6.Conclusions

SCHER concludes that, from a scientific point of view, the use of NHPs, at the present time, is essential for scientific progress in a number of important areas of disease biology research and in safety testing:

− Development of pharmaceuticals, in particular safety testing, to assess potential toxicity in animals to identify unacceptable adverse reactions in humans. For specific pharmaceuticals including antibodies, NHPs may represent the most relevant animal model for specific aspects of toxicity testing because of their close similarity to humans.

− Understanding the pathophysiology of infectious diseases such as HIV/AIDS, where the NHP is the only susceptible species and therefore the only useful animal model to study the disease, and to develop safe and effective vaccines and therapies.

− Learning how complex brains of primates, humans included, are structured and function. Again, NHPs are the best model due to their close similarity to humans with regard to brain complexity and function. In addition, NHPs are the best model for some human brain conditions and have been critical in developing and testing novel and current treatments.

− Developing and testing xenotransplantation methodologies.

Source & ©: SCHER,  The need for non-human primates in biomedical research, production and testing of products and devices (2009),
Section3.1.6 Conclusions, p.-21.

3.4.3. Recommendations

Based on the available scientific evidence, at the present time, SCHER sees no valid scientific reasons to support a discontinuation of the use of primates in basic and applied research, or in the development and testing of new drugs. However, this position should be regularly reviewed in the light of validated alternatives that are constantly being developed.

To comply with all “Three Rs” alternatives, SCHER recommends investment and activities in the following areas of NHP use:

1. All uses of NHPs should be carefully justified before any work begins and any such justifications should be carefully monitored by the Member States and subjected to a retrospective evaluation at the end of each project.
2. Better research strategies (including the development of non-invasive methods which can be used in human volunteer studies, and the development of new in vitro and in silico technologies) should be supported and encouraged. Although the replacement of NHP use by new technologies should be encouraged, it should always be subjected to a careful scientific evaluation.
3. The anticipated benefits of NHP studies and scientific progress in developing alternative methods should be regularly assessed to ensure that validated alternatives are adopted as soon as they are reasonably and practical available. Regular meetings (e.g. workshops, conferences) should be organised by those involved in NHP research and supported by the Commission, to stimulate scientific discussion and exchange of information between researchers within the various fields of NHP use and scientists working actively with, and advocating for, alternative methods.
4. The development of accessible and comprehensive databases and collaborative users networks should be promoted covering aspects such as data sharing, tissue sharing, exchange of knowledge and information e.g. on animal models, alternative to animal models, in house data and experience, in order to further the “Three Rs” in European NHP research. Such networks should also include laboratories engaged in developing replacements for NHP use with non-animal methods.
5. Networking of facilities breeding and maintaining NHPs for experimental purposes should be supported by those involved in NHP research and by the Commission, in order to advance knowledge and competence in the areas of animal housing, care and breeding. The objectives should be the improvement of animal welfare, the standardisation of procedures and methods, and the availability of NHPs. Implementation of improved standards of husbandry and care, as laid out in Commission recommendation 2007/526/EC (Council of Europe Appendix A) should be achieved at the earliest opportunity to ensure good welfare and to support good science. This should include higher biosafety level facilities.
6. The predicted degree of severity for NHP work should be limited to moderate. However, derogation for predicted severe severity should be approved and justified by the competent and independent authority of the MS where the work is taking place.
7. In the specific context of NHP use, the use of other non-primate species, such as minipigs or genetically modified rodents, to replace NHPs should be further investigated and encouraged.
8. The use of wild-caught NHPs for experiments should be discouraged for both scientific and animal welfare reasons.
9. In view of the concerns raised by NHP users, breeders and suppliers regarding the transition towards using only F2 generation or higher in research, an evaluation of the animal welfare, scientific and economical aspects of such a use is recommended to take place on a regular basis, starting 5 years after the implementation of the revised Directive 86/609/EEC.
   
   3.4.4. Other recommendations
10. All work done supported from sources in Europe with partners outside the EU should meet European standards of care and welfare in order to promote good science. Compliance should be assured by the research partners.
11. Sectors using NHPs and developing alternatives should organise global networks to exchange information on the “Three Rs”, including giving clear and consistent guidance on the criteria for the use of NHPs, supported by the Commission.
12. Further negotiations with Non-European countries (such as the USA and Japan) for international harmonisation should be carried out on the requirements for safety testing of pharmaceuticals and vaccines (e.g. animal numbers, study design, endpoints) involving NHPs.

3.5.Promote research into areas that advance replacement, reduction and refinement in the use of NHPs in scientific procedures

• Further research in the use of genetically altered animal models or other suitable mammalian species in testing of vaccines and pharmaceuticals. However, the ethical aspects of such use should also be considered.
• Improved understanding of pathophysiological mechanisms(e.g.cell-cell interactions in the development of a toxic response) of toxicity to improve in vitro test systems to actually resemble the complex interactions likely to be involved in the pathophysiological responses to toxicants to serve as basis to develop better in vitro models.
• Improved understanding of the comparative physiology of the immune system in NHPs, humans and other non-rodents to develop improved models with higher predictivity.
• Research into the recognition of suffering in NHPs, and its classification, its avoidance, and its alleviation should be carried out as quickly as possible. This would help in addressing the predicted adverse effects and severity bands, any retrospective assessment of animal suffering, and limiting any pain and distress. A better understanding of social needs and housing requirements of NHPs and how to meet them best in experimental environment is also needed.
• Research to develop new accessible technologies should be supported in order to refine experimental procedures on NHPs. Such technologies might be non-invasive procedures such as imaging, biocompatible implants such as telemetry and data loggers. It is conceivable that their refinement will also greatly benefit non- invasive research of human brain structures. Furthermore, access for researchers using NHPs to facilities with newer technologies should be encouraged.
• Further research into use of stem cells to restore organ function may replace the need for NHPs in xenotransplantation,
• More research into an improved understanding of the neural basis of brain neurodynamic responses for the physiological assessment of the welfare of primates and scientific validity is required.
• More research is required into the stress-reducing potential of social housing, environmental enrichment, positive reinforcement training and other measures of behavioral management in relation to experimental procedures with NHPs.
• Creative work to stimulate or inactivate deep brain regions (Roth et al., 2007) may provide in the future novel means for non-invasive brain studies, including safe human brain research that could reduce, and, in specific instances, replace NHP experiments. Such work should be funded and encouraged.

Source & ©: SCHER,  The need for non-human primates in biomedical research, production and testing of products and devices (2009),
Section 3.4.3 Recommendations, Section 3.4.4 Other recommendations and Section 3.5 Promote research into areas that advance replacement, reduction and refinement in the use of NHPs in scientific procedures, p.27-29.