SPS 2024 -- The E14/S7B Q&A guidelines introduce the concept of “double negative” (negative hERG and negative in vivo QTc) nonclinical data, which can be used along with negative Phase I clinical QTc data to substitute for a clinical thorough QT study in specific cases (Q&As 5.1 and 6.1). For the in vivo QT assay, best practice recommendations require characterization of individual study sensitivity, verification of independence QTc from heart rate, demonstration of test facility sensitivity and pharmacological translation to human using a positive control. We have previously validated E14/S7B Q&A compliant in vivo QT assays in dog and nonhuman primate (NHP). The objective of this work was to perform the validation in the minipig as the third non-rodent species commonly used for cardiovascular safety assessment. 

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