Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data

SIMPLE SUMMARY: Before any new medicine can be administered to humans, or new chemical marketed, some tests using animals such as fish, mice, rats, rabbits, dogs, or monkeys are performed in order to satisfy the legal requirements of international regulatory and government agencies. These assess the potential for harmful side effects in humans or species found in the environment and to explore how the compound is processed within the body. The housing conditions and procedures performed (such as dosing of compounds and removal of small blood samples) are designed to minimize any pain, suffering, distress, or lasting harm that may be experienced by the animals. These refinements improve animal welfare but can also improve the data quality. Examples of new processes, technologies, or equipment that have been introduced within some UK facilities are shared in this article and provide opportunities to benefit many more animals undergoing testing across the world in the future. ABSTRACT: During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package. These refinements benefit the welfare of fish, mice, rats, rabbits, dogs, minipigs, and non-human primates (NHPs) whilst maintaining or improving data quality within general toxicology, metabolism, and other studies and can also bring efficiencies to processes that benefit study costs and timings. Examples are shared which cover the following topics: social housing of dogs and NHPs, surgical refinements in the rat bile duct cannulation model for collection of data for metabolism studies, whether fasting is really required prior to clinical pathology sampling, and the use of microsampling for toxicokinetics.