Research using animals plays a vital role in the development of all new medicines: the complexity of our bodies mean they cannot yet be fully modelled by tissue cultures or computers, so animals have to be used to help understand diseases and the effects of new medicines on the body, as they are the closest model we have to the human body.
However, our industry is strongly committed to the 3Rs (reducing, replacing and refining the use of animals in research). This is demonstrated in our recent publication, available online as an advanced article, which shows increasing use of in vitro (non-animal) techniques in member companies.
The pharmaceutical industry voices a strong commitment to the 3Rs, and research is ongoing across the bioscience sector into new, non-animal, technologies. But how do we know what tests companies are really using in drug development? What progress in being made in the use of new technologies? And what gaps remain?
Our Nonclinical and Biological Discovery Expert Network recently carried out a study to begin to answer these questions. Member companies were surveyed on their use of in vitro assays (non-animal tests in dishes or test tubes) in preclinical safety testing for new medicines in the last 20 years. We received responses from seven ABPI member companies: four pharmaceutical companies and three Contract Research Organisations.
The results showed that the use of in vitro techniques has increased massively in preclinical safety testing over the last 20 years, with a continued year on year increase since 2005. Indeed more than 70% of all in vitro assays captured by the survey were used since 2010. Together with our paper published earlier this year, which showed that the pharmaceutical industry is increasingly publishing scientific research papers with a 3Rs focus, this is an encouraging sign that pharmaceutical companies are serious about their commitment to the 3Rs and are making good progress in this area.
So what does an increase in the use of in vitro assays mean? Unfortunately it doesn’t mean that animal tests will be completely replaced in the near future. A small number of the in vitro assays included in the survey do directly replace animal tests, such as skin irritation tests. The majority however are used for early screening of potential new medicines, alongside animal tests. Ultimately though, these tests still lead to a reduction in the use of animals.
As an example, the potential for new medicines to be genotoxic (that is to damage the DNA in cells, which can lead to cancer) can be investigated in vitro using cultured cells. However, these tests are not sufficient to fully identify the potential to cause cancer, so regulations still require animal tests to test for carcinogenicity in potential new medicines. Using in vitro tests early in development though screens out the compounds which have the highest probability of causing cancer. These compounds are then never progressed to safety tests using animals. This ultimately makes the research of new medicines more efficient, and reduces the overall use of animals, as only the most promising candidates reach the stage of animal safety testing.
In addition to showing an overall increase in the use of in vitro tests, the study highlighted which areas of safety testing they are used in. The fields with highest in vitro assay use were the key areas of genotoxicity, safety pharmacology, and ADME (absorption, distribution, metabolism and excretion) studies. Very few in vitro tests were used in developmental and reproductive safety testing, or testing for adverse effects on the immune system. These are complex biological systems involving the interaction of multiple cells, tissues, and organs, and more basic research or technological advancement is needed before they can be well modelled in vitro or by computer (in silico).
Finally, the study looked at how different in vitro techniques have been taken up by industry: some showed very rapid uptake, whereas others showed a more gradual uptake across several years. In some cases this is for scientific reasons, for example where a new technique is not fully evaluated or established, but in others there may be opportunities for the uptake of new technologies to be improved to have a more rapid impact on animal use.
Overall, this study demonstrates that the pharmaceutical industry is taking its commitment to the 3Rs seriously. Companies are increasingly making use of in vitro technologies in drug development, which should both reduce the overall use of animals in research and improve the efficiency of medicines development. However, it also highlights areas for future focus, including where few in vitro assays are currently available, and how uptake could be encouraged.
The NC3Rs works closely with the pharmaceutical industry and is supported by our members through the ABPI-NC3Rs collaboration. In their new ten year strategy they highlight the need for both continued research into new technologies and encouraging uptake of new techniques. They have played a key role in supporting the pharmaceutical industry in their progress in the 3Rs over the last ten years, and will continue to do so in the next. New technologies are helping the sector move a step along the road towards replacing the use of animals in the development of new medicines, and the pharmaceutical industry is welcoming these advances with open arms.
Dr Nicola Platt
R&D Policy Officer