In 2013, the European Union banned the sale of all cosmetics products and ingredients that had been tested on animals. The continued need for regulatory data drove rapid innovations for ground-breaking in vitro safety evaluations. This move towards in vitro toxicity and sensitivity testing has been widely endorsed by consumers, who generally believe that the development of beauty products does not justify the suffering of animals.
Now, there is growing pressure to move away from animal testing in pharma too. As well as lobbying by animal rights activists in the West, preclinical investigators themselves are increasingly concerned that animal experimentation may be based on a scientifically flawed premise. More than 90% of drugs entering clinical trials fail, usually for reasons of toxicity and poor efficacy that were not detected in animals. Findings such as these have led many to re-evaluate the value of animal studies in drug development.1–3
Brian W. Dutko, President & CEO of Pion – a science-based company providing innovative technology, solutions, support and scientific expertise – explains: “During the drug development process, researchers are tasked with collecting in silico and in vitro data and asked to try and predict in vivo human responses. How scientists have bridged this gap in the past has been by assessing injectable formulations within animal models before moving into humans. Although it is relatively accessible to view immune responses in animal models, due to the vast amount of previous research, there have been worrying examples of how some observations do not correlate to how the human body will react to a formulation.”
A matter of safety
In particular, and probably of greatest concern, there is mounting evidence that animal testing is not always a good predictor of drug safety. Animal safety data cannot be confidently translated to humans.
For example, in 2006, a life-threatening 'cytokine storm', not predicted by pre-clinical safety testing, rapidly occurred in all six healthy volunteers during the phase I clinical trial of the CD28 superagonist monoclonal antibody (mAb) TGN1412. Despite causing no concerns in animal tests using 500x the dose used in the phase I study, the human volunteers immediately fell critically ill, and the single dose left them all with long-term complications.
Similarly, in January 2016, a drug developed for a range of neurological disorders, BIA-102474-101, caused deep brain haemorrhage and necrosis in all five human volunteers during a phase I trial; one of these volunteers died. The underlying mechanism that caused the acute neurotoxicity of this molecule remains unknown.
Following these and other cases in which animal tests failed to detect safety concerns, it is argued that animal testing has only retained it acceptability in drug development because clear alternatives have not yet been identified. Yet the cosmetics industry has demonstrated that a variety of novel in vitro technologies could offer effective alternatives that are ‘human relevant’, and in fact those technologies could be better at modelling human diseases and drug responses.
Furthermore, drug developers and pharma ingredients manufacturers might already be further along this path than you think.
Human cell and tissue models
Use of human cells and tissues in vitro provide effective opportunities for the assessment of safety and efficacy of new medicines. At its simplest level, this comprises straightforward in vitro assays, such as blood cells, pancreatic islets, and various smooth muscle preparations.
Various cell-based assays have shown superior human relevance for toxicity and bioavailability, compared with animal models. For example, in vitro liver cell models for liver toxicity testing are reported to show better predictive accuracy than animal tests using rodents, in part due to poor indication of animal study results to disease phenotypes observed in heterogeneous human populations.
Critics will say that these assays do not adequately model the complexity of the wh...
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