Secondary pharmacology data to assess potential off-target activity of new drugs: A regulatory perspective

Abstract

In vitro secondary pharmacology studies are considered to be valuable and cost-effective tools to identify and to predict possible adverse effects of drugs in early human clinical trials based on unintended pharmacodynamic activities. For new molecular entities, there is a general preference for a broad panel of targets. Also useful are detailed descriptions for methodology, data expression in tabular and/or graphical format and discussion of the biological significance of any findings. When used with other standard non-clinical assessments, such data help to reduce drug attrition due to safety concerns and increase the chances that safe and effective therapeutics will be made available to the public. Variability in the timing, type, extent and format of submitted secondary pharmacology data limits the usefulness of the data during early stages of the drug safety review process. This Correspondence addresses these issues by providing current regulatory perspectives on important aspects of in vitro secondary pharmacology data, as well as discussing how such data are assessed and when such data are usually submitted. Important remaining issues are identifying specific targets, target categories and biological functionalities that should constitute a minimal in vitro panel, and determining how primary versus secondary panels should be defined. Although some of the more general considerations involved in target selection are discussed here, several recent publications are available that provide additional rationale for target selection under specific circumstances3-10.