Priorities in the development of alternative methodologies in the pharmaceutical industry.

Promotion of animal welfare is an underlying and laudable goal for toxicologists and there is good reason to adopt practical, focused, investigative approaches towards this aim. Pharmaceutical regulatory toxicology can be subdivided into the areas of systemic (target organ), reproductive, genetic and topical toxicology, as well as immunotoxicology and oncology. These areas can be assessed for prioritisation as to where adoption of measures to promote any or all of the 3 Rs (reduction, replacement, refinement) would lead to the most tangible benefit for animals. These measures can range, for example, from replacement of animal experimentation with alternative in vitro techniques, to adoption of regulatory protocols that reduce the number of animals required. This paper is confined to consideration of in vitro technology in terms of reducing/replacing laboratory animal use, and a suggested list of criteria for prioritisation is potential for:- Regulatory acceptability Reducing development cost Reducing animal numbers Promoting welfare aspects Elucidating toxic mechanisms Usefulness in compound selection Advancing the science of toxicology Clear messages emerge from such an analysis which could influence prioritisation of the application of in vitro toxicology from the standpoints of animal welfare, feasibility and resources.