Michael K. Pugsley

TL;DR: This work has updated the guidance on the design and execution of experiments and the definition, classification, quantification, and analysis of all types of arrhythmias, and urges investigators to adopt the conventions.

TL;DR: The regulatory guidelines (ICHS7B) recommending inhibition of the delayed rectifier K+ current (IKr) carried by human ether‐a‐go‐go-related gene (hERG) channels in cardiac cells (the hERG test) as a ‘first line’ test for identifying compounds inducing QT prolongation, have limitations, some of which are outlined here.

TL;DR: It is recommended that it is not appropriate to conduct an in vitro hERG assay as part of a preclinical strategy for assessing the heart rate corrected QT interval (QTc) prolongation risk of mAbs and other types of biologicals and more appropriate to assess QTc risk by integrating cardiovascular endpoints into repeat-dose general toxicology studies performed in an appropriate non-rodent species.

TL;DR: ICH S7A core battery studies are implemented by most of the responding companies with a clear trend of an enhanced submission of renal and GI studies and a diversity of approaches for conducting abuse liability studies, which primarily use the methods of self-administration and drug discrimination.

TL;DR: A literature search to identify both human and non‐rodent animal studies that assessed QT signal concordance between species and identified drugs that prolonged or did not prolong the QT interval found excellent agreement between QT results in humans and non-rodent animals.