The use of human tissue in safety assessment.

INTRODUCTION: The safety-related failure of drugs during clinical phases of development is a significant contributor to drug attrition, wasting resources and preventing treatments from reaching patients. A lack of concordance between results from animal models and adverse events in the clinic has been identified as one potential cause of attrition. In vitro models using human tissue or cells have the potential to replace some animal models and improve predictivity to humans. METHODS: To gauge the current use of human tissue models in safety pharmacology and the barriers to greater uptake, an electronic survey of the international safety assessment community was carried out and a Safety Pharmacology Society European Regional Meeting was organised entitled 'The Use of Human Tissue in Safety Assessment'. RESULTS: A greater range of human tissue models is in use in safety assessment now than four years ago, although data is still not routinely included in regulatory submissions. The barriers to increased uptake of the models have not changed over that time, with inadequate supply and characterisation of tissue being the most cited blocks. DISCUSSION: Supporting biobanking, the development of new human tissue modelling technology, and raising awareness in the scientific and regulatory communities are key ways in which the barriers to greater uptake of human tissue models can be overcome. The development of infrastructure and legislation in the UK to support the use of post-mortem or surgical discard tissue will allow scientists to locally source tissue for research.

Human tissue models for a human disease: what are the barriers?

Asthma represents an area of significant unmet medical need, with few new drugs making it to the clinic in the past 50 years. Much asthma research is currently carried out in non-human models. However, as asthma is a uniquely human condition, it is difficult to translate findings from these models to efficacious therapies. Based on the results of a survey of the UK asthma research community carried out jointly between the NC3Rs, Asthma UK, the UK Respiratory Research Collaborative and the Human Tissue Authority, we propose that more emphasis be placed on the use of human tissue studies to provide more relevant models that better translate to the clinic and which reduce the reliance of the asthma community on less predictive animal models.

Animal models of asthma: value, limitations and opportunities for alternative approaches.

Asthma remains an area of considerable unmet medical need. Few new drugs have made it to the clinic during the past 50 years, with many that perform well in preclinical animal models of asthma, failing in humans owing to lack of safety and efficacy. The failure to translate promising drug candidates from animal models to humans has led to questions about the utility of in vivo studies and to demand for more predictive models and tools based on the latest technologies. Following a workshop with experts from academia and the pharmaceutical industry, we suggest here a disease modelling framework designed to better understand human asthma, and accelerate the development of safe and efficacious new asthma drugs that go beyond symptomatic relief.