New CiPA cardiac ion channel cell lines and assays for in vitro proarrhythmia risk assessment

New cardiac safety testing guidelines are being developed as part of the FDA’s Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aims to remove the reliance on screening against the hERG channel by expanding the panel to include other human ventricular ion channels such as Nav1.5, Ca_V1.2, K_V4.3/KChiP2.2, K_ir2.1 and K_V7.1/KCNE1. In addition, the CiPA working groups have recently identified two additional ion channel assay readouts required for in silico models to reliably predict proarrhythmia. The first is a ‘late’ Na_V1.5 assay, as inhibition of persistent inward current can affect repolarisation and mitigate proarrhythmia (e.g. Ranolazine). The second is a kinetic hERG assay that measures drug trapping using the Milnes voltage protocol(1) and improves the prediction of proarrhythmia risk(2). Here we describe validation of these additional CiPA assays on the gigaseal QPatch48 automated patch clamp platform.