Predictive value of the hERG assay for anticipating the arrhythmogenic potential of new drugs

• QT prolongation and torsades de pointes are significant cardiac safety concerns. • The ICH S7B (non-clinical) and E14 (clinical) guidelines identify proarrhythmic risk. • The in vitro hERG assay is a sensitive measurement but it is not specific. • CiPA initiative improved specificity compared with the hERG assay plus TQT study. • AI and hiPSC-derived cardiomyocytes are key for drug testing. A prolonged QT interval is a risk factor for developing torsades de pointes – a potentially fatal drug-related ventricular arrhythmia. The in vitro hERG assay plays a relevant part in this context, presenting predictive value for anticipating the arrhythmogenic potential of new drugs. However, its value for predicting clinical outcomes remains a matter of debate. This review article addresses the several milestones in the field, highlighting the International Council for Harmonization (ICH) S7B and E14 guidelines, and the comprehensive in vitro proarrhythmia assay (CiPA), as well as the current limitations and future challenges.