DSTC International Collaborative Research Published in Scientific Reports
The results of the international collaborative research on best practices for hERG channel evaluation, which we have been advancing since 2022, have been published in the journal Scientific Reports. This collaborative research was conducted with five facilities, including DSTC, under the leadership of the Health and Environmental Sciences Institute (HESI). We are currently conducting similar international collaborative research on the CaV1.2 and NaV1.5 channels.
Paper Title
Multi-laboratory comparisons of manual patch clamp hERG data generated using standardized protocols and following ICH S7B Q&A 2.1 best practices
Research Background
In TdP (Torsades de Pointes) risk evaluation, the extent of drug's safety margin due to hERG inhibition is assessed by comparing it with the threshold established for known TdP-inducing agents.
However, conventional literature data often include systematic differences such as variations in temperature, stimulation conditions, and voltage protocols, along with random errors, which makes it difficult to define a reliable hERG safety margin.
ICH S7B Q&A 2.1 recommends following best practices, such as verifying protocols under conditions closer to physiological settings and using relevant exposure concentrations.
However, the extent to which these practices improve data precision has not been fully evaluated.
To address this, the study conducted hERG assays for 28 compounds using standardized manual patch-clamp protocols and assessed, through multi-laboratory comparisons, how applying best practices contributes to improved data reproducibility and reduced inter-site variability.
