Chairs: Erika Ferrari & t.b.a.
Cardiac safety remains a critical bottleneck in drug development, often responsible for late-stage attrition and market withdrawal. New Approach Methodologies (NAMs) combining in silico and advanced in vitro systems offer innovative, human-relevant strategies to assess proarrhythmic and cardiotoxic risks earlier and more accurately in the drug development pipeline.
In silico cardiac models, based on biophysically detailed simulations of human cardiomyocyte electrophysiology, enable virtual drug testing by predicting drug effects on ion channel activity, action potential dynamics, and arrhythmia susceptibility. These models, including population-based and multiscale approaches, provide a cost-effective, high-throughput means of assessing variability and dose-dependent risk and are central to regulatory-oriented frameworks such as CiPA (Comprehensive in vitro Proarrhythmia Assay).
Heart organoids – three-dimensional, stem cell-derived microtissues – recapitulate key aspects of human cardiac development and function, including spontaneous beating, cellular heterogeneity, and tissue maturation. Characterized through transcriptomic, structural, and functional profiling, organoids are increasingly recognized for their value in long-term and developmental cardiotoxicity assessments.
Heart-on-chip platforms integrate human cardiac cells into microfluidic devices that simulate the dynamic biomechanical and electrophysiological environment of the native myocardium. Validated through reproducible functional endpoints such as beat rate, contractility, and conduction velocity, these systems offer real-time, clinically relevant insights under controlled mechanical and perfusion conditions.
Together, these NAMs support a robust, multi-modal approach to cardiac safety testing, reducing reliance on animal models and improving translatability to human outcomes. The increasing interest of regulatory bodies for NAMs, supported by initiatives from agencies such as the FDA and EMA, underscores their potential to be integrated into standard safety pharmacology workflows. Continued efforts in validation, standardization, and cross-sector collaboration are key to ensuring their broader adoption and regulatory impact.
Speakers
- Bettina Lickiss – Mechanistic Class-Specific Cardiac Safety Profiling Using a Microphysiological System Mimicking Native Heart Biomechanics
- Christian Maass – MPSlabs’ Virtual Testing Center: Expanding DigiToCs for Advancing Qualification and Validation of Cardiac-on-Chip Systems
- Roberta Visone – uHearts: Mechanically Stimulated Beating Heart-on-Chip Models to Advance Cardiac Safety
- Udo Kraushaar – BEYOND CIPA: EMERGING ELECTROPHYSIOLOGICAL PLATFORMS IN CARDIAC SAFETY TESTING
- Afaf Fizazi – Could succination lead to Cardiotoxcity