Comprehensive in vitro Proarrhythmia Assay (CiPA): Pending issues for successful validation and implementation

Abstract Introduction The Comprehensive in vitro Proarrhythmia Assay (C i PA) is a nonclinical Safety Pharmacology paradigm for discovering electrophysiological mechanisms that are likely to confer proarrhythmic liability to drug candidates intended for human use. Topics covered Key talks delivered at the ‘C i PA on my mind’ session, held during the 2015 Annual Meeting of the Safety Pharmacology Society (SPS), are summarized. Issues and potential solutions relating to crucial constituents [ e.g. , biological materials (ion channels and pluripotent stem cell-derived cardiomyocytes), study platforms, drug solutions, and data analysis] of C i PA core assays are critically examined. Discussion In order to advance the C i PA paradigm from the current testing and validation stages to a research and regulatory drug development strategy, systematic guidance by C i PA stakeholders is necessary to expedite solutions to pending and newly arising issues. Once a study protocol is proved to yield robust and reproducible results within and across laboratories, it can be implemented as qualified regulatory procedure.