09.09.2020 - A deep-dive into CiPA
CiPA - Comprehensive in vitro Proarrhythmia Assay
The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative aims to replace the preclinical hERG current assay required under the ICH S7B safety pharmacology guidelines and clinical TQT study, which provides a surrogate marker of Proarrhythmia, with more translationally relevant assessments of proarrhythmic risk (Sager et al., 2014). CiPA intend to achieve this by evaluating proarrhythmic risk of evolving drug candidates based on an understanding of the electrophysiologic mechanisms responsible for proarrhythmia linked to Torsades de pointes (TdP) and QT prolongation.
Benchmarking best practices and calibration standards for improved proarrhythmic assessment [Download the Publication Here]
Journal of Pharmacological and Toxicological Methods - Vol 103
Screening compounds for activity on the hERG channel using patch clamp is a crucial part of safety testing. Automated patch clamp (APC) is becoming widely accepted as an alternative to manual patch clamp in order to increase throughput whilst maintaining data quality. In order to standardize APC experiments, we have investigated the effects on IC50 values under different conditions using several devices across multiple sites.
Automated patch clamp instruments SyncroPatch 384i, SyncroPatch 384PE and Patchliner, were used to record hERG expressed in HEK or CHO cells. The CiPA compounds were used to investigate effects of voltage protocol, incubation time, labware and time between compound preparation and experiment on IC50 values. The here developed benchmarks are decisive for employing patch clamp results to in silico experiments as implied in the CiPA paradigm, and fundamentally enable the assessment of translatability to clinical findings.