Repaving the Regulatory Road From Animal Models to New Approach Methods

Abstract ID 100172 Poster Board 014 Background: There is increasing interest in the development and adoption of alternative methods aimed at replacing, reducing, and refining (3Rs) the use of animals in preclinical biomedical, pharmacological, and regulatory research. These "new approach methods" (NAMs) which include any technology, methodology, approach, or assay that can be used to investigate the effects and mechanisms of action of drugs or chemicals with a focus on the 3Rs are likely to play an important role in future public health policies. It is therefore essential that investigators and other stake holdersstakeholders remain apprised of the state of the art as it relates to this emerging and rapidly evolving area of preclinical research. Methods: A working group of toxicology experts who are also members of the Scientific Liaison Coalition (SLC), performed a collective in-depth review of the literature in order to effectively evaluate the current state for as it pertains to the 3Rs and the adoption of NAMs in regulatory toxicology and preclinical drug discovery. The findings from this review are presented in a narrative format. Successes and challenges related to selecting appropriate animal models and NAMs for effectively deciphering mechanisms of chemical/drug action and identifying adverse effects are discussed. Results: The results of this SLC working group review revealed that animal models have contributed to many important biological discoveries. We also find that in vitro replacement assays, including engineered microsystems and newer human cell-based assays especially when these are combined with computational models have the potential to advance our understanding of the mechanisms of action of chemicals which in turn are likely to improve the regulatory decision-making landscape. We also identified several limitations related to the use of animal models and NAMs indicating the ongoing need for continued improvements in both. Conclusions: The results of this comprehensive review of the current state of the art suggest it is unlikely that all animal studies will be replaced with NAMs in the immediate future. It is however also likely that future improvements in these new methods and technologies will pave the way for NAMs to become an increasingly important component in preclinical drug discovery and in regulatory decisions making. The successful adoption of NAMs will depend on future contributions from biologists, computational modelers, toxicologists, and veterinarians committed to developing these alternatives to animal models. Hybrid methods that successfully combine animal models with NAMs are likely to also make important contributions to the field of preclinical research.