ICH Publishes Updated E14/S7B Q&As on QT/QTc and Proarrhythmic Risk

The International Council for Harmonisation (ICH) has published the updated ICH E14/S7B Questions & Answers (R1).

The new document provides clarification on the clinical and nonclinical assessment of QT/QTc prolongation and proarrhythmic risk and replaces the previous combined version published in 2022.

Purpose of the Updated Q&A

The Q&A complements the existing ICH E14 and ICH S7B guidelines by addressing practical implementation questions.

ICH states that the updated document provides clarification across several areas, including:

• electrocardiogram methodology;

• study design;

• concentration-response modelling;

• best practices for in vitro nonclinical studies;

• best practices for in vivo nonclinical studies.

Relationship With ICH E14 and ICH S7B

ICH Q&A documents are intended to support implementation of harmonised guidelines.

Although separate from the guideline text itself, they are designed to be used together with the corresponding ICH guidelines and provide practical clarification where implementation questions arise.

In this case, the updated Q&A should be considered alongside ICH E14 and ICH S7B.

Clinical and Nonclinical Cardiac Safety Assessment

ICH E14 and ICH S7B address complementary aspects of cardiac safety assessment.

The updated Q&A supports a more consistent approach to evaluating:

• QT/QTc interval prolongation;

• proarrhythmic potential;

• ECG data;

• clinical study design;

• concentration-response relationships;

• nonclinical in vitro studies;

• nonclinical in vivo studies.

The objective is to support scientifically robust and globally aligned assessment of cardiac risk during medicine development.

Global Harmonisation

ICH explains that Q&A documents are produced when needed to clarify existing guidelines and respond to practical implementation questions.

The updated E14/S7B Q&A is therefore intended to support more consistent application of these principles by both regulatory authorities and industry.

This harmonised approach can help reduce variability in how cardiac safety evidence is generated, interpreted and assessed across jurisdictions.

Patient Safety

The updated ICH E14/S7B Q&A, together with the underlying guidelines, supports the scientific evaluation of QT/QTc prolongation and proarrhythmic risk.

ICH states that this contributes to improved protection of patients from cardiac adverse effects associated with new medicines.

Impact on Pharmaceutical and Clinical Development Teams

For pharmaceutical companies, clinical development teams, nonclinical safety teams and regulatory professionals, the updated Q&A is relevant because it provides additional implementation support for cardiac safety assessment.

Stakeholders should pay particular attention to:

• ECG methodology;

• QT/QTc evaluation;

• concentration-response modelling;

• clinical study design;

• in vitro cardiac safety studies;

• in vivo nonclinical studies;

• integration of clinical and nonclinical evidence;

• consistency with ICH E14 and ICH S7B;

• regulatory interpretation of proarrhythmic risk.

For organisations developing new medicines, the key message is that the updated Q&A should be reviewed alongside ICH E14 and ICH S7B to ensure cardiac safety strategies remain aligned with current harmonised implementation expectations.