The research and development landscape has changed considerably since these regulatory requirements have been in place, with new in vitro and in silico technologies available to evaluate safety in addition to the standard in vivo approach. Opportunities to refine and reduce animal use within toxicology studies have been explored (4) and some flexibility in guideline testing requirements have been incorporated, for example, chronic toxicity studies are not required for drugs indicated for acute/short-term use, or in life-threatening indications. With emerging technologies, there is now the opportunity to consider the relevance of the animal models used in the development of NCEs.