We provide high-quality, cost-effective and rapid-turnaround, specialist GLP testing services against hERG using the conventional whole-cell patch-clamp technique.

GLP compliant hERG testing is mandatory under the ICH S7B guidelines, which states that in vitro IKr and in vivo QT assays described in Sections 2.3.1 and 2.3.2 when performed for regulatory submission should be conducted in compliance with good laboratory practice (GLP).

Our services have been audited and approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and are performed in accordance with the Food and Drug Administration (FDA) best practice guidelines.

Read about the importance of GLP hERG testing to ensure data regarding a drug’s potential to cause cardiac arrhythmias is reliable, giving confidence that it can be used in regulatory decision making.

Metrion are co-author of a paper in which GLP hERG data were generated for the three reference compounds using ICH best practices in order to understand intra and inter laboratory variability in the data and to assess a suitable hERG safety margin under these conditions.

Read more about the paper by Derek J. Leishman, Jessica Brimecombe, William Crumb, Simon Hebeisen, Steve Jenkinson, Peter J. Kilfoil, Hiroshi Matsukawa, Karim Melliti, Yusheng Qu, Supporting an integrated QTc risk assessment using the hERG margin distributions for three positive control agents derived from multiple laboratories and on multiple occasions., Journal of Pharmacological and Toxicological Methods, Volume 128, 2024, 107524, ISSN 1056-8719, https://doi.org/10.1016/j.vascn.2024.107524.

Platform

Manual patch-clamp

GLP hERG test system

CHO

Temperature

36 ± 2°C

Number of test concentrations

4

Positive control

Ondansetron

Required for IND submission?

Yes

Dose-formulation Analysis (DFA)

Yes, using a GLP compliant partner

The ICH S7A and ICH S7B guidelines provide regulatory guidance on performing safety pharmacology studies for human pharmaceuticals. Most Investigational New Drug (IND) applications for small molecules include pharmacological assessments against the human ether-à-go-go related gene (hERG) potassium channel, which should be conducted in compliance with GLP principles.

The human ether-à-go-go related gene (hERG) encodes the pore forming subunit of the rapidly activating delayed rectifier potassium current (IKr), which plays an important role in contributing to the repolarisation of ventricular cardiomyocytes.

The action potential duration of ventricular cardiomyocytes corresponds to the QT-interval of the electrocardiogram; therefore, inhibition of IKr can lead to prolongation of the cardiac action potential and the QT interval. Prolongation of the rate corrected QT interval beyond 440 ms is associated with an increased risk of arrythmias, such as the polymorphic ventricular tachycardia, Torsade de Pointes (TdP).

Several drugs have been withdrawn from the market, or had their use severely restricted, due to their proarrhythmic liability. Many of those drugs have been identified as hERG blockers and, consequently, ICH S7B guidelines were introduced that include guidance on evaluating the effect of new chemical entities against hERG using GLP principles. The implementation of hERG screening in drug discovery has had a significant contribution in reducing the development of proarrhythmic drugs.

Metrion Biosciences

If you have any questions or would like to discuss your specific assay requirements, we will put you directly in touch with a member of our scientific team. Contact us today to discover more.