ICCVAM Biennial Report 2018-2019

Two FDA Centers, the Drug Evaluation and Research and Biologics Evaluation and Research, pursue international harmonization of nonclinical recommendations for human pharmaceutical development through their engagement with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH brings together regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of drug registration. ICH's mission is to achieve greater harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner. These activities reduce repetition of studies and reduce and refine animal use in overall drug development. New guidances recently approved will continue to contribute to the 3Rs as will future guidances that are currently being developed or revised.

FDA Q&A documents issued on ICH guidances on toxicokinetics and anticancer pharmaceuticals are discussed elsewhere in this report. The Center for Drug Evaluation and Research is engaged with other ongoing activities of ICH.

• Revision of the ICH S5 (R3) guidance on reproductive toxicology was ongoing through 2018 and 2019. The revisions propose to expand circumstances under which the outcome of “preliminary embryofetal development studies” (per ICH M3(R2)) could support clinical trials, which could lead to fewer definitive studies being conducted. In addition, the revised guidance proposes basic principles that would assist in the development and potential regulatory use of alternative assays for evaluating adverse effects on embryofetal development.
• An ICH working group is also discussing revisions to guidances related to assessing proarrythmic potential (ICH S7B and E14). The potential changes to these guidances could include incorporation of multi-ion channel assays, in silico models, in vitro human primary cell assays, and induced pluripotent cardiomyocyte assays, in addition to in vivo evaluations.