High-quality, cost-effective and rapid turnaround, testing against hERG

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 I_Kr 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.

GLP hERG assay

Metrion provides hERG screening services using the conventional whole-cell patch-clamp technique. These services are performed in accordance with the FDA’s best practice guidelines and in compliance with:

1. UK GLP Regulations, SI 1999 No 3106; amendments, SI 2004 No. 994.
2. OECD No 1 Principles on Good Laboratory Practice and Monographs. 

The experiments are performed using the FDA’s recommended voltage protocol and experimental solutions at physiological temperature.

Concentration verification via chemical analysis of dosing formulations (Dose Formulation Analysis, DFA) is an obligatory requirement for GLP studies submitted in IND filings and is performed by our preferred GLP accredited partner. 

Supporting an integrated QTc risk assessment using the hERG margin distributions for three positive control agents derived from multiple laboratories and on multiple occasions

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.

GLP hERG assay overview

Platform	Manual patch-clamp
GLP hERG test system	CHO
Temperature	36 ± 2°C
Number of test concentrations	4
Positive control	Ondansetron
Required for most IND filings?	Included under the ICH S7B guidelines
Dose-formulation Analysis (DFA)	Yes, using a GLP compliant partner

Why perform hERG screening?

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 (I_Kr), 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 I_Kr 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. 

Ion channel screening resource library