The use of primates in the safety testing of monoclonal antibodies prior to clinical trials could be reduced by the wider application of existing technologies, according to a paper published in the February issue of Nature Reviews Drug Discovery.
However, the paper goes on to say that if the application of such technologies is to result in a reduction in numbers, there will also need to be regulatory acceptance of these types of non-conventional studies.
The use of monoclonal antibodies, a type of human therapeutic protein, is predicted to rise due to successes in treating cancer and other major diseases. A key stage in ensuring the safety of these drugs is to conduct tests in animals and, due to the high species specificity of monoclonal antibodies, there is a concern that more monkeys or even chimpanzees, will end up being used.
To address this concern the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), in collaboration with the Association of the British Pharmaceutical Industry (ABPI), held an international workshop last year to discuss issues relating to primate use in the development of monoclonal antibodies. Delegates came from the pharmaceutical and biotechnology industries, academic institutions and regulatory bodies. A report of the meeting was produced and a summarised version appears as a Perspectives paper in the journal Nature Reviews Drug Discovery.
At the meeting, a hypothetical pathway was developed where primates were not used. In this pathway, existing technologies were identified that have the potential to provide enough information that primates would not have to be used for certain tests. For example, surrogate antibodies, which are animal-specific versions of the human drugs, could be developed which can then be tested in animals such as mice and rats or, alternatively, genetically-altered rodents could be created that express the human form of the molecule that the drug targets.
Dr Kathryn Chapman, Programme Manager, NC3Rs and lead author on the paper, said: "We took a novel approach to thinking about the reduction of the use of primates by getting together experts from around the world and asking them to imagine that primates were no longer available, perhaps due to regulatory change or supply issues. They then set out to identify what obstacles, if any, there were to getting a new monoclonal antibody approved for human clinical trials with out having data from primates available."
"What came out first is that there isn't a 'one size fits all' approach and every drug would be judged on a case-by-case basis. There was wide support at the workshop for the idea that in the development of some monoclonal antibodies, the use of genetically altered rodents, surrogate molecules, in vitro data and a cautious approach to using humans, could realistically minimise the use of primates, while safeguarding human patients and volunteers."
Dr Vicky Robinson, chief executive of the NC3Rs, said: "Nobody wants to use animals and our ultimate goal is to replace all animal use, but we are not going to achieve that overnight. In the meantime, we must aim to reduce animal use wherever possible and our belief is that when the cumulative suffering of monkeys and rodents is compared, on balance, it is more ethical to use a rodent. Public opinion tends to reflect this position, with more concern expressed for the use of monkeys in research and testing than for other animals."
Some participants from the workshop were invited to join an expert working group which is now looking at the questions and obstacles raised. A key part of the work is companies sharing information and, encouragingly, this has now begun to happen. The group hopes to report their findings by the end of 2007.
According the Home Office annual statistics on animal use 21.7% of animals used in 2005 were in pharmaceutical research and development. Of these, 45% were used for toxicological purposes. In terms of primate use, 73% of the marmosets and 84% of the macaques are used in pharmaceutical research and development. The reason for focusing on the drug development pathway for monoclonal antibodies is that their high specificity means there will be no 'off-target' effects, which makes the assessment of their effect more straightforward than for new chemical drugs.