Researchers writing in the Journal of the Royal Society of Medicine are warning that current research models and regulation are blocking the development of human-relevant approaches to drug discovery and are perpetuating animal-based approaches. The UK currently has world-leading research in this area but significant investment in non-animal technologies is taking place in the US and Europe.
The researchers describe the technologies as representing a completely new, human-focused and systems-biology based approach to drug discovery. They incorporate a range of in vitro, in silico and human in vivo methodologies and are driven by the need to reduce costs and increase the speed and accuracy of drug discovery. Evidence is beginning to emerge that the new technologies may be better at predicting adverse drug reactions and drug toxicity than safety testing in animals.
Examples of the new technologies include organoids which are simplified in vitro versions of organs, capable of modelling specific functions of the organ, and organs-on-chips that mimic key aspects of the physiology and function of human organs.
The researchers say that the key problem with the current system of drug development is the poor ability of existing pre-clinical models to reliably predict safety and efficacy in humans. Human drug-induced toxicities that are poorly predicted by animal safety studies include toxicities of the liver, the heart, the immune system, the skin, the endocrine system and the central nervous system.
Poor human predictivity results in only a small proportion of drug candidates translating into treatments for humans, despite having first appeared safe and effective in animal studies.
Lead author Kathy Archibald, of the Safer Medicines Trust, said: “New technologies need to be fit-for-purpose. In other words, if they are intended to be used to test drug safety they need to be acceptable to regulators. Unfortunately, however, regulators currently only accept safety data derived from new technologies if the latter have been validated against historical animal data.”
Ms Archibald continued: “This makes little sense as the tests must predict how the drugs will behave in humans, not animals, and means that the new tests cannot succeed if the drug in question affects animals differently from humans, which is often the case.”
The researchers say that funding incentives could disrupt the current institutional lock-in to animal research by prioritising funding for human-based biomedical research over funding for ‘improved’ animal models. They are also calling for regulations to be amended to allow innovation to flourish, pointing to the development in Japan of human-induced stem cell therapies.
Better science for safer medicines: the human imperative (DOI: 10.1177/0141076818812783) by Kathy Archibald, Katya Tsaioun, J. Gerry Kenna and Pandora Pound will be published by the Journal of the Royal Society of Medicine at 00:05 hrs (UK time) on Friday 16 November 2018.
The link for the full text version of the paper when published will be: http://journals.sagepub.com/doi/full/10.1177/0141076818812783
For further information or a copy of the paper please contact:
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