5. When primates cannot be replaced, how could their use be reduced?
The SCHER opinion states:
Careful analysis of the results of tests on rodents could reduce the number of primates needed
Source: Understanding animal research
3.4.The opportunities for the reduction and refinement of NHP use in areas where no replacement can be foreseen in medium or long term
- Reductions in routine toxicity testing in NHPs may be achieved by a more careful evaluation of results of biotransformation studies in other mammalian species, including other non-rodents. An improved screening for biotransformation may help to identify the animal species most similar to humans and may thus reduce the use of NHPs in cases when the dog is not a suitable non-rodent species. However, this may only shift testing to other mammals such as the minipig. Improved information exchange between industry may also help to reduce NHP uses as discussed for a reduction in dog use for safety assessment (Smith et al., 2002).
- Overly restricting the re-use of NHPs may result in an increased number of NHPs being used for experimental purposes, and care has to be taken to differentiate re- use from continued use.
- The use of NHPs in reproductive toxicity studies (now 15-20 animals per group, in 4 groups including control) with therapeutic monoclonal antibodies may be reduced. In the standard test design, the number of animals per dose group is selected to enable detection of the incidence of malformations. This standard study design involves giving antibody to this number of pregnant females between days 20 and 50 of pregnancy. Placental transfer in this period is very low to absent and, therefore, the risk of skeletal malformations induced by monoclonal antibodies is very low. Conventional studies on embryo-foetal development (so-called segment 2 studies) to look for consequences of in vivo transfer over the human placental barrier could be combined with peri-postnatal studies. The period at risk is the latter part of pregnancy where deviations can be induced in more functional parameters (kidney function, immune function).
- A reduction of NHP use in safety testing of pharmaceuticals is also possible by harmonisation requirements for safety testing (for example regarding group sizes) by different regulatory agencies. A high variety in the number of NHPs used for safety testing, depending on the character of the product and its potential use in humans, is observed for biotechnology-derived pharmaceuticals registered in Europe between the late 1980s and 2003. A very low number is used for testing of diagnostic antibodies (used only once), whereas a much higher number of NHPs (around 300) may be used for testing a therapeutic monoclonal antibody. A reduction may be possible by improving and harmonizing the study designs needed for safety testing.
- The application and implementation of the “Three Rs”-concept in the use of NHPs could be improved by facilitating greater collaboration between establishments, and by enhancing the exchange of information leading to a reduction in primate use as experiments will not have to be repeated. For example, a European network of laboratories using NHPs as well as laboratories working to replace animal experiments should be established to allow access to a pool of information and resources and the sharing of expertise, tissues and ideas for implementing the “Three Rs”. Accessible databases, like those developed for neuroanatomical and pathology data could be very useful in this context.
- More transparent information for choice of species and justification including numbers of animals used for specific testing should be available in public assessment reports.
- Genetic and genomic research and the increased possibilities to create genetically modified humanised rodent models may lead to a possible reduction and partial replacement of NHPs models used for the development of vaccines and treatments against infectious diseases. However, a time frame for the successful completion of these studies cannot be given. It may be possible to reduce the need for NHPs in xenotransplantation by using stem cell research and tissue engineering. However, these areas are still in an early research stage and far away from clinical applications.
Source & ©: SCHER,
Section 3.4 The opportunities for the reduction and refinement of NHP use in areas where no replacement can be foreseen in medium and long term, Section 3.4.1 “Reduction”, p.26.