The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative represents one of the most important revisions in cardiovascular safety since the ICH S7B and ICH E14 guidelines were implemented more than a decade ago. Although the current regulatory pathway has been successful in preventing torsadogenic drugs from reaching the market, it is now understood that QT prolongation is not highly specific for proarrhythmic risk. Thus a finding of hERG block or QT prolongation may eliminate drugs that are not proarrhythmic from development. To qualify the CiPA paradigm, an international multi-disciplinary team of regulatory, industry and academic scientists are working together to develop and validate the assays and approaches in the CiPA pathway. To support this effort, a set of compounds with well-defined cardiac electrophysiology and known clinical outcomes was identified by a subteam of expert clinicians and cardiac electrophysiologists who discussed, selected and categorized 28 compounds into high, intermediate and low risk of Torsade de Pointes (TdP) based on published reports, FDA AERS database, other data sources and expert opinion. The set of 28 drugs was divided into a set of 12 drugs to be used for training and calibration, with the remaining 16 used for validation. This poster will discuss the drugs selected for study and the anticipated impacts on ICH E14 guidelines including efforts to develop new electrocardiographic biomarkers for confirming CiPA in vitro and in silico predictions that can be applied in phase 1 clinical trials without a Thorough-QT study.