Ethical standards in animal research
Before any medicine can be brought to market, clinical trials must first be conducted to establish that the medicine is both efficacious and well tolerated. However, before human clinical trials for new medicines can proceed, regulatory bodies worldwide require efficacy and safety data from studies conducted on animals. As research seeks new treatment solutions for complex diseases, such as neurodegenerative disorders, animal testing continues to be necessary in order to facilitate these developments.
Animal models are still indispensable in some research areas. They provide the only way of modelling the effects of a new medicine on an entire organism, with all its organs and the complex interactions that take place in the body. Long-term effects can often only be demonstrated in animal models, and that is also why authorities responsible for licensing drugs still insist on them as part of the approval process.
Read moreabout Roche's principles for care and use of animals in research.
Encouraging the development of alternative methods
However, Roche is pioneering and promoting the application of innovative in silico and in vitro approaches in preclinical research. In silico, computational, model-based simulations help us to identify promising drug candidates faster and with more precision. Modern, in vitro molecular biology techniques enable us to better translate findings from cellular systems to optimised animal models to humans. They also lead to a better understanding of diseases and provide valuable insights for a more individualised targeted approach to medicine.
One of these methods is to model human physiology outside the living organism, for example on a chip, in a lab, or to use computer models to test the behaviour of a medicine in the body. This approach should allow researchers to replace a great deal of animal testing in the early preclinical development stage or future major advances. Using such methods, Roche has reduced the number of animals in experimental use by 50% over the past 14 years.
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To further advance alternative methods, Roche sponsors the Roche 3Rs Award, presented every two years. Launched in 2008, this award aims to increase awareness and promote dialogue among employees and scientists about the 3Rs, to encourage the discovery of alternative methods to animal testing, and to enhance Roche’s mission to support innovation and advancement of animal welfare standards globally.
Reduce
Minimise the number of animals used
Refine
Minimise any animal discomfort and improve welfare
Replace
Avoid or substitute the use of animals
Reduce
With careful design, sophisticated statistical techniques and modern imaging, it is often possible to significantly reduce the number of animals used in research while still generating valid results, truly adding to the knowledge base.
Refine
This refers to decreasing the potential for causing animals distress and continuously seeking advancements in animal husbandry, care practices and environmental enrichment to provide the best possible conditions for animals.
Replace
Research animals are either replaced by methods not involving animals (absolute replacement) or by methods using only the cells or tissues of animals (relative replacement). Such alternative methods include cell and bacterial cultures, computer simulations, mathematical modelling, and the use of microphysiological human or animal systems.
Real world data makes models smarter
Laboratory experimentation and animal testing give us information on the effect of a new medicine and its distribution in the body. Computer models enable us to transfer those results to humans using complex simulations, allowing us to predict dosages and effects before direct human testing begins. In the context of these models we also use real world data. It is difficult to predict effects in humans since every patient has different features of a disease. If we can build in specific characteristics of different patient populations into a test model, we will be better able to anticipate the effects of a medicine in the human body. Currently, animal data is still required as a reference for computer models. Once real world data sources are more established, we will be able to reduce animal experiments even further.
Patient-derived organoids
No toxicity is observed in organoids (above)
Organoid toxicity and cell death (above)
With the help of patient-derived organoids we are able to model important aspects of a human organ outside a living organism. In this case, we mimicked critical parts of the gut and predicted adverse events of potential medicines in the human body. This promising approach minimises the number of animal experiments and studies while making preclinical drug development programmes more precise and predictive for clinical trials. The pictures show an untreated organoid (top left) where no toxicity is observed, as evidenced by a lack of signal from a fluorescent probe for cell death (top right). In contrast, the two pictures at the bottom depict organoid toxicity and cell death (shown by the green signal on the right) based on drug intervention.
Organoids have the potential to revolutionise the way we discover and develop medicines. With the Institute of Human Biology (IHB),Roche is breaking new ground and driving development in the field of organoids.
Governance and exchange: Keeping the dialogue going
The Ethical Committee of Animal Welfare at Roche comprises representatives from all research organisations within the Roche Group. The Committee advises on strategic matters related to animal welfare practice and policy, reviews and, where necessary, proposes changes and actions related to animal testing. It advances the 3Rs within Roche and also assists in communications with external governance and regulatory bodies.
When conducting animal studies, every project includes a detailed explanation of the research purpose, the likely effects on the animals, and the reasons why the results cannot be obtained using other methods. These research protocols are reviewed by state veterinary authorities in the European Union and Institutional Animal Care and Use Committees (IACUCs) in the United States and other parts of the world.
We regularly engage with animal welfare organisations to improve our mutual understanding and to exchange views on animal welfare-related topics. For example, we communicate regularly through Interpharma (Swiss Pharmaceutical Companies Association) with animal welfare organisations such as Swiss Animal Protection (SAP).