Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development.

Area of Science:

• Biomedical Engineering
• Toxicology
• Drug Discovery

Background:

• Growing need for human-relevant models in drug development to reduce animal testing.
• Advances in in vitro systems and new approach methodologies (NAMs) are crucial.

Purpose of the Study:

• To discuss the utility and integration of NAMs in preclinical drug safety assessment.
• To identify challenges and opportunities for adopting NAMs in regulatory submissions.

Main Methods:

• Workshop convened by the Health and Environmental Sciences Institute (HESI) in May 2024.
• Discussions focused on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), microfluidic systems (e.g., BioFlux™), and engineered heart tissues.
• Review of regulatory perspectives and case studies.

Main Results:

• hiPSC-CMs, microfluidic systems, and engineered heart tissues show promise for predicting cardiac failure modes.
• NAMs demonstrated superior predictivity compared to traditional methods in emerging case studies.
• Regulatory bodies acknowledge the potential but highlight the need for standardization and validation.

Conclusions:

• Collaboration between academia, industry, and regulatory bodies is essential for robust validation and adoption of NAMs.
• Successful integration of NAMs can refine cardiovascular drug discovery and reduce attrition rates.
• These efforts support a transition to more ethical and efficient preclinical testing paradigms.