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

New cardiac safety testing guidelines are being finalised, as part of the FDA’s Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aim to remove the over-reliance on screening against the hERG channel by expanding the panel to include hNav1.5, hCav1.2, hKv4.3/KChiP2.2, hKir2.1 and hKv7.1/KCNE1 human cardiac ion channels. In addition, the CiPA working groups have recently identified two additional in vitro assays required for in silico models to reliably predict proarrhythmia. The first is a ‘late’ sodium current assay, as inhibition of persistent inward current can affect repolarisation and mitigate proarrhythmia (e.g. ranolazine). The second assay quantifies the degree of drug trapping in the hERG channel using the Milnes voltage protocol⁽¹⁾, which can improve the prediction of proarrhythmic risk⁽²⁾.

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