Back to the future: Safety pharmacology methods and models in 2013

Abstract

Safety pharmacology continues to seek to validate and refine methods for use in preclinical detection of adverse effect liability. Almost uniquely in pharmacology, drug safety assessment by safety pharmacologists is driven by the need for elaboration and validation of methods for detecting drug actions. This is the 10th consecutive year that the Journal of Pharmacological and Toxicological Methods (JPTM) has published themed issues arising from the annual meeting of the Safety Pharmacology Society (SPS), most recently held in Phoenix, AZ in 2012. The SPS is now into its 13th year as a distinct (from Pharmacology and Toxicology) discipline that integrates safety pharmacologists from industry with those in academia and the various global regulatory authorities. Some of the unique sessions of the 2012 meeting included (i) Oncology Therapies, (ii) Assessment of Cardiac Function and (iii) The Growing Role of Safety Pharmacology. This issue of JPTM reflects these themes. As with the previous 10 issues of the Journal, the manuscripts in this issue encompass a broad spectrum of safety pharmacology topics including application of state-of-the-art methods in keeping with the directive of the ICH S7A guidance document emphasizing “…the use of new technologies and methodologies in accordance with sound scientific principles…” study conduct and data analysis, processing and evaluation. This includes some exciting new applications with well validated in vitro and ex vivo safety pharmacology models, refinements in high throughput screening methods with application for use in early safety pharmacology assessments, modified supplemental safety methods meant to evaluate potential adverse pharmacodynamic effects on organ system functions not addressed by the core battery and heart rate variability in non-human primates (NHP). Additionally a series of fascinating articles examining the effects of known drugs on electrophysiological and contractile function in human induced (iPSC-CM) and embryonic (hESC-CM) stem cells are presented. A historical review on hERG channel electrophysiology and channel characterization, efforts of the HESI Cardiac Technical Safety Committee since its inception and an overview of the dynamic and vibrant Safety Pharmacology Society (SPS) are also included in this issue.