An FDA/CDER nonclinical perspective on the use of hiPSC-CM data for cardiovascular safety assessment and regulatory decisions.

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a New Approach Methodology (NAM) used in regulatory submissions to the U.S Food and Drug Administration (FDA). This article builds on the previous FDA analysis using a new search strategy to provide an updated landscape of hiPSC-CM studies submitted to the FDA for review. The current search method is more comprehensive than the previous ones, emphasizing the importance of standardized keywords in study titles for easier identification of NAMs submitted to FDA. Here the authors report an increase in hiPSC-CM studies submitted to FDA, with most using the multielectrode array (MEA) platform. In this new analysis, the authors observed that the study methodology, context of use (COU), and reasons for submission are often unclear, despite their importance for regulatory acceptance and review. hiPSC-CM study results are not discussed in many archived reviews, suggesting limited impact on regulatory decisions. Detailed reporting to characterize the clinical relevance of findings and systematic submission of hiPSC-CM studies to better understand their predictivity compared to familiar nonclinical assessment methods are key components from a Pharmacology/Toxicology perspective to increase regulatory use of this subset of NAMs.