June 22nd, 2016
11am to 12pm EST

Sponsored by

Webinar Description:

Eurofins Pre-Clinical Cardiac Safety Screening for Proarrythmia. Drug-induced arrhythmia is a concern for regulatory agencies and pharmaceutical industry because it may manifest following the approval of new drugs and cause serious harm to patients. Currently, drug-induced arrhythmogenic liability is evaluated based on the ICH S7A/B and ICH E14 guidelines, using in vitro inhibition assays of hERG K+ current and in vivo QT interval assessment to estimate the risk of delayed ventricular repolarization (QT prolongation)-related arrhythmia in humans. Because there are no reliable markers for proarrhythmia, QT prolongation has been used as a surrogate marker of Torsade de Pointes (TdP). This strategy has been successful in ending drugs withdrawn from the market due to drug-induced arrhythmia but induced drug attrition at late stage development. Therefore, more comprehensive assays are urgently needed for translation of nonclinical proarrhythmic potential to humans. Accordingly, CSRC- HESI- FDA meeting held in July 2013, abolition of ICH E14 and revision of ICH S7B with a new paradigm shift from evaluating QT prolongation to evaluating proarrhythmic activity using a comprehensive in vitro proarrhythmia assay (CiPA) was proposed. CiPA consists of three components: assessment of drug effects on key cardiac ion channels in vitro, in silico reconstruction of human ventricular cellular electrophysiology using ion channel dataset, and confirmation of the in vitro and in silico prediction by determining electrical activity of human stem cell- derived ventricular cardiomyocytes. Eurofins Drug Discovery Support will show validation data to demonstrate Eurofins is operationally ready for evaluating proarrhythmic activity using CiPA.

Learning Objectives:

• Drug induced Proarrythmia
• New Paradigm for Cardiac safety Evaluation: CiPA
• Candidate Currents for CiPA

Speaker:

Rengi Renganathan

Senior Scientist

Drug Discovery