Metrion's Cardiac Safety Screening services incorporate all three components of the Comprehensive In vitro Proarrhythmia (CiPA) initiative.
- Automated electrophysiology screening against an expanded panel of six cardiac ion channels, including hERG.
- In silico modelling using electrophysiology data from the expanded ion channel panel.
- Confirmation of in silico predictions using translational assays employing human iPSC-derived cardiomyocytes
Metrion is a member of the HESI Cardiac Safety committee and, as part of its role in the HTS sub team, is involved in validating automated screening assays. The company also has access to multiple commercially available iPSC-derived cardiomyocyte cell lines, which have been fully validated in-house.
The FDA and selected industry stakeholders are currently working towards launching a revised regulatory framework to assess the cardiac safety of new chemical entities. Known as the CiPA initiative, this new framework aims to improve upon the existing FDA regulations (ICH S7B and ICH E14) by introducing an updated workflow for cardiac safety assessment. Under current guidelines potential new therapeutics undergo initial assessment for activity against the human ether-a-go-go (hERG) ion channel, before progressing to preclinical animal models and finally a thorough QT interval study (TQT) in the clinic. The CiPA initiative will extend the early electrophysiology-based screening to include effects on a panel of cardiac ion channels with a key role in control of the ventricular action potential waveform. This expanded electrophysiology data will be used to create in silico modelling data to supplement data from additional phenotypic assays, such a data package should significantly improve the accuracy of identification of compounds with true cardiac liability.