Industry evidence sets animal welfare benchmark

A multi-national industry collaboration has set new animal welfare guidelines since reviewing limits to determine the maximum-tolerated dose of a drug candidate used in short-term toxicity studies. The project, led by the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and AstraZeneca, used data from toxicity studies of up to seven days duration and concluded that a new upper limit of 10% bodyweight loss could be used as a primary endpoint for selecting the highest dose of a drug that could be tolerated in dogs and rats. The results of the study, which involved 15 pharmaceutical companies and contract research organisations have been published in Regulatory Toxicology and Pharmacology.

Along with the new recommended limits, an alert system has been developed to determine when the maximum-tolerated dose has been reached. While bodyweight loss is used here as an objective measurement, the presence of other clinical signs is also incorporated to add value to this practical advice. These standardised assessment criteria will minimise the adverse effects experienced by thousands of animals used in pharmaceutical development each year.

Maximum-tolerated dose studies are important from both a scientific and ethical perspective. They are used to make decisions on the progression of potential candidate drugs across a range of therapeutic areas. They also set the dose level for subsequent studies that allow for regulatory approval.

This approach to re-assessing bodyweight loss has the potential to be translated to other research areas including pharmacology and efficacy studies and short-term toxicity studies with chemicals.