Animal research debate in the UK Parliament

The use of dogs in testing remains an area of public concern and developing alternatives is a key focus of the NC3Rs/industry collaboration. A flagship programme is the work that we have led in partnership with the pharmaceutical industry to identify whether drugs can be safely tested using one rather than two animal species. We have been able to deliver this work because of the long-standing funding we receive from the Association of the British Pharmaceutical Industry for a programme manager post in the NC3Rs. 

International guidelines for pharmaceuticals typically require toxicity testing to be performed on two animal species – a rodent such as mice or rats, and a “non-rodent” such as dogs, minipigs or monkeys – in order to provide information on the safety of potential new medicines before human clinical trials. We have facilitated a large international data sharing initiative with pharmaceutical companies and medicines regulators to explore the feasibility of shifting to one species only without compromising human safety. By analysing data provided by 18 companies on 172 drugs we have provided evidence that this shift to a single, usually rodent, species is possible for molecule types such as biotherapeutics (e.g. monoclonal antibodies). We are currently working with industry and regulators to explore this further, as well as leading a new phase of data collection and analysis to investigate if this approach could also be expanded to small molecule drugs. This work has the potential to reduce the use of dogs as the so-called “second species” and as part of our efforts to make this a reality we have committed £2.6M through our CRACK IT Challenges innovation programme for the development of virtual dog organs and tissues for assessing the toxicity of pharmaceuticals. This is an exciting and ambitious project with seven pharmaceutical companies from the UK, mainland Europe and North America working with us to provide the data to build the model. In addition, we are also collaborating with the EU’s Innovative Medicines Initiative funded eTRANSAFE consortium who are providing animal study data from some of their 12 international pharmaceutical company partners for the project.  

As well as our efforts to find alternatives that enable testing in dogs to be avoided, we have a large programme that focuses on reducing the actual numbers used and improving animal welfare where dogs are still currently required for assessing the safety of new medicines. Again, this is an area where data sharing on study designs has been very powerful and by acting as an honest broker for cross-company data sharing, we have published recommendations on how to reduce the number of dogs used (either within each dose group that is tested or by reducing the overall number of doses of a drug that are assessed). We have also published recommendations on minimising the use of dogs as “recovery animals” for the registration of new medicines. These are additional groups of animals that are included in tests to determine whether animals can recover from any adverse effects caused by the compound being assessed. Data we have collected recently shows that our recommendations are having an impact with recovery animals generally being included in fewer studies and in fewer dose groups. The percentage of studies including recovery animals on first-in-human enabling studies for small molecule drugs has decreased from 65% in 2014 to 39% in 2017. 

Where dog use is considered necessary it is essential to minimise any suffering they might experience and we have also published recommendations on this. This includes limiting the amount of weight dogs lose on dose setting studies (weight loss is a sign of suffering) as well as promoting the housing of dogs in compatible groups during telemetry studies of cardiovascular function, rather than housing the dogs on their own which can be stressful for them. The use of microsampling techniques where only very small blood samples are taken has also been an area we have championed.  Microsampling is a refined blood sampling procedure which is quicker and less stressful to animals than traditional methods of obtaining blood for analysis during toxicity studies. 

Moving on to the second e-petition, 633591. The term “NAMs” is in the petition text. This is a term that is used variably by different organisations as an abbreviation for non-animal methods or new approach methodologies. The term new approach methodologies specifically refers to technologies that replace the use of animals in assessing chemical or drug toxicity (i.e. the subject of e-petition 633591), whereas the term non-animal methods (used in the text of e-petition 633591) is generally used to describe approaches which replace the use of animals irrespective of purpose.  

Replacing the use of animals in research and testing is central to the NC3Rs mission. Over the past five years, we have committed £32.4M for research and innovation in the development of replacement technologies, with 32% (£10.4M) of this specifically for NAMs that replace the use of animal toxicity tests. The funding for NAMs has been used to support a range of scientific and technological advances. This includes new computational models, for example to predict the potential of chemicals in the environment to disrupt the function of human thyroid hormones, an area that without innovation will lead to large rises in animal use. Much of our funding commitment on NAMs has been for cell-based alternatives. This includes a new body-on-chip device for testing drugs and chemicals which uses 3D printing to create compartments that replicate the human heart, lungs, kidney, liver and brain, all connected by channels that mimic the human circulatory system, through which new drugs and chemicals can be pumped. This research was funded by an NC3Rs PhD studentship in partnership with Unilever and was recently featured in The Guardian, highlighting the public interest in this area. 

Working internationally is critical for the development and adoption of NAMs and we have effective partnerships in place with various organisations around the world. Last year we hosted a conference in collaboration with the US-based Health and Environment Sciences Institute on NAMs for safety assessment, from aspiration to implementation. During the pandemic, we worked with the USA’s validation agency, NICEATM, to jointly establish an expert working group to coordinate the use of microphysiological systems to help reduce animal studies in COVID-19 research. We have also recently completed a major piece of work commissioned by the World Health Organisation to review their regulations on animal testing requirements for vaccines and other biologicals with a focus on identifying opportunities for the 3Rs. We were really pleased to secure funding from the Bill & Melinda Gates Foundation to deliver this work and it is great that the funding has been recently renewed so that we can support a range of follow-on projects. These include accelerating the global adoption of the monocyte activation test to replace the use of rabbits in identifying substances in vaccines which can cause fever and the removal of the mouse weight gain test for assessing toxicity where it is not scientifically justified.

Closer to home we have been working with scientific stakeholders to drive the policy and regulatory changes in the UK that are necessary for the acceptance of NAMs in practice, by encouraging the UK to adopt a new strategic framework for chemical regulation that fully embraces new approaches to safety assessment that avoid the use of animals. The work builds on a workshop that we co-organised last summer with Unilever on Opportunities for the UK to develop world-leading chemicals regulation. A few weeks ago with our collaborators at the British Toxicology Society we published a policy paper based on the expert discussions at the workshop. The paper calls for the UK to use the opportunities presented by exiting the EU to adopt a modern and flexible approach to chemicals regulations that embraces the use of NAMs. It sets out the need for investment in this area, a coordinated approach between all the relevant UK regulatory agencies to deliver the new regulatory framework, and the harmonisation of approaches worldwide. A key step is connecting those developing NAMs with industry and regulatory end-users so that there is a greater understanding of the potential of NAMs on the one hand and the needs of those who will ultimately be making decisions based on data from NAMs on the other. I am really pleased that we have recently announced that we are launching a NAMs Network to catalyse these interactions with our first event in April. 

Globally there is considerable interest and investment in NAMs. This is not just because of the opportunities to avoid the use of animals but also because of the potential of NAMs to provide more accurate and relevant data on drug and chemical safety and increase the speed and efficiency of toxicity testing compared to animal studies. There has also been a growing political commitment to advancing the use of NAMs as illustrated by the change in UK government policy on worker and environmental safety assessment of cosmetic ingredients last year, as well as the FDA Modernization Act 2.0 in the USA at the end of 2022, which has been widely heralded as a major shift in policy. There are some areas of safety testing such as the assessment of skin sensitisation where NAMs are already being successfully used in place of animal studies. However, despite increasing aspirations to use NAMs, their acceptance by regulatory authorities remains relatively limited. There are various reasons for this, including continued regulatory requirements for data from “tried and tested” animal studies in most industry sectors, the extent of which varies between geographical regions. Building the confidence to move away from practices which have been in place for decades, coupled with the complex and lengthy processes often required to change policy and regulations means that the widespread adoption of NAMs will take time. I am however optimistic. I think we have reached a tipping point and while we still need considerable scientific and technological innovation there is a momentum building that I am confident will accelerate and result in significant changes in the next decade. Supporting this transition will continue to be a key activity for the NC3Rs – we have the track record in place through the brilliant work of my colleagues and the long-standing effective partnerships in place nationally and internationally with our outstanding partners and funders who like us are determined to make a difference.