A negative hERG assay, suggesting that the drug has a low likelihood of hERG block-mediated QTC prolongation and TdP, is defined as having a safety margin (i.e., concentration that inhibits 50% of hERG current (IC50) divided by relevant clinical exposure level) larger than the margin threshold derived from a series of reference drugs with known TdP risk3 (see ICH S7B Q&A 1.1). This evidence concerns the gene KCNH2 and torsades de pointes.