2021 Volume 11 Issue 1 Pages 75-81
In 2009, the ICH-S7B guideline was issued focusing on the non-clinical risk assessment for the QT interval prolongation of pharmaceuticals. After the issuance of the ICH-S7B guideline, the technique of culturing has been established for homogeneous myocardial cells (myocardial-like cells) from human iPS/ES cells with functions such as contraction similar to human myocardial tissue expressing ion channels that control heartbeat. These cells are readily available on a commercial basis. Research institutes in Japan and the United States have studied to apply these myocardial-like cells to cardiovascular risk assessment of pharmaceuticals. Human iPS-derived myocardial-like cell (iPS-CM) expressing ion channels that control the action potential of myocardium is validated to utilize for comprehensive proarrhythmia risk assessment. Currently, the ICH E14/S7B Implementation Working Group is discussing the requirements for using the test systems as part of nonclinical safety studies in New Drug Application. This article provides the usefulness in human risk prediction regarding cardiovascular safety evaluation using iPS-CM, which has a function similar to that of newly developed cardiomyocytes with human biological function. The points of consideration are also shown regarding the validation and interpretation of test results required when establishing a new assay system as regulatory studies.
