Refinement, reduction, and replacement of animal use for regulatory testing: future improvements and implementation within the regulatory framework

Many are critical of how regulatory testing practices have evolved and become established—critical both of the sci-entific rational and the animal welfare costs. The test of whether we are more enlightened than our predecessors will be whether, armed with more powerful scientific insights and a better understanding of animal welfare, we can ensure that the best animal welfare and the best science drive and shape future developments in regulatory testing. Conduct-ing the most humane animal-based regulatory testing re-quires establishing and maintaining a constructive dialogue between stakeholders and acknowledging the common ground that unites. Inclusive processes with stakeholders prepared to offer public, rational justifications for their poli-cies and processes are essential if best practice is to be identified and implemented. There is general agreement that the best animal welfare results in the best science; that regu-latory requirements based on an understanding of mecha-nisms and early relevant biomarkers result in elegant and valid science. Thus, "alternative " methods enabling replace-ment, reduction, or refinement (the 3Rs) are in reality often more scientifically "advanced " and scientifically valid methods. These principles provided the incentive and framework for recent initiatives in the United Kingdom to enhance the quality of the data prepared for regulatory sub-mission while better protecting the welfare of the animals used. Some remaining 3R opportunities are explored in this paper, and some of the commonly encountered myths about regulatory testing and perceived barriers to change are chal-lenged. Current "threats " may indeed offer opportunities for ensuring that sound science and the best animal welfare underpin developments in regulatory testing. Key Words: animal testing alternatives; animal welfare; laboratory animal science; preclinical drug evaluation; regu