title: Promoting Adoption of the 3Rs through Regulatory Qualification.
abstract: One mechanism to advance the application of novel safety assessment methodologies in drug development, including in silico or in vitro approaches that reduce the use of animals in toxicology studies, is regulatory qualification. Regulatory qualification, a formal process defined at the the U. S. Food and Drug Administration and the European Medicines Agency, hinges on a central concept of stating an appropriate "context of use" for a novel drug development tool (DDT) that precisely defines how that DDT can be used to support decision making in a regulated drug development setting. When accumulating the data to support a particular "context-of-use," the concept of "fit-for-purpose" often guides assay validation, as well as the type and amount of data or evidence required to evaluate the tool. This paper will review pathways for regulatory acceptance of novel DDTs and discuss examples of safety projects considered for regulatory qualification. Key concepts to be considered when defining the evidence required to formally adopt and potentially replace animal-intensive traditional safety assessment methods using qualified DDTs are proposed. Presently, the use of qualified translational kidney safety biomarkers can refine and reduce the total numbers of animals used in drug development. We propose that the same conceptual regulatory framework will be appropriate to assess readiness of new technologies that may eventually replace whole animal models.
authors.affiliation: Elizabeth G. Walker, PhD, is the Director of Regulatory Strategy and Submissions at the Critical Path Institute in Tucson, AZ. Amanda F. Baker, PharmD, PhD, is an Associate Professor of Medicine at the University of Arizona Cancer Center and a Research Scientist at the Critical Path Institute, both in Tucson, AZ. John-Michael Sauer, PhD, is the Executive Director of the Predictive Safety Testing Consortium at the Critical Path Institute in Tucson, AZ.
authors.forename: Elizabeth Gribble
authors.initials: EG
authors.lastname: Walker
authors.affiliation: Elizabeth G. Walker, PhD, is the Director of Regulatory Strategy and Submissions at the Critical Path Institute in Tucson, AZ. Amanda F. Baker, PharmD, PhD, is an Associate Professor of Medicine at the University of Arizona Cancer Center and a Research Scientist at the Critical Path Institute, both in Tucson, AZ. John-Michael Sauer, PhD, is the Executive Director of the Predictive Safety Testing Consortium at the Critical Path Institute in Tucson, AZ.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Baker
authors.affiliation: Elizabeth G. Walker, PhD, is the Director of Regulatory Strategy and Submissions at the Critical Path Institute in Tucson, AZ. Amanda F. Baker, PharmD, PhD, is an Associate Professor of Medicine at the University of Arizona Cancer Center and a Research Scientist at the Critical Path Institute, both in Tucson, AZ. John-Michael Sauer, PhD, is the Executive Director of the Predictive Safety Testing Consortium at the Critical Path Institute in Tucson, AZ.
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Sauer
mesh_terms: D023401:Animal Use Alternatives / Q000331:legislation & jurisprudence; D000818:Animals; D015415:Biomarkers; D055808:Drug Discovery / Q000331:legislation & jurisprudence*; D023421:Models, Animal; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence*
chemical_list: D015415:Biomarkers
keywords: drug development tools; regulatory qualification; safety biomarkers