Opportunities to minimise animal use in pharmaceutical regulatory general toxicology: A cross-company review

Toxicity studies in animals are carried out to identify the intrinsic hazard of a substance to support risk assessment for humans. In order to identify opportunities to minimise animal use in regulatory toxicology studies, a review of current study designs was carried out. Pharmaceutical companies and contract research organisations in the UK shared data and experience of standard toxicology studies (ranging from one to nine months duration) in rodents and non-rodents; and carcinogenicity studies in the rat and mouse. The data show that variation in study designs was primarily due to (i) the number of animals used in the main study groups, (ii) the use of animals in toxicokinetic (TK) satellite groups, and (iii) the use of animals in off-treatment recovery groups. The information has been used to propose a series of experimental designs where small adjustments could reduce animal use in practice, while maintaining the scientific objectives.

► A cross-company review of regulatory toxicology study designs has been carried out. ► The data shared has been used to develop proposals with the potential to minimise animal use. ► These include practical ways of reducing the number of animals to obtain TK data. ► Incorporation of fertility assessment into general toxicology studies. ► Consideration of strain, transgenic alternation and control groups in carcinogenicity studies.