UK MHRA Guidance: Compliance with ICH E6 GCP in UK, Quality and Risk proportionality, & Clinical Investigations for Medical Devices

The UK clinical trial regulatory framework is undergoing a major transformation with the implementation of updated ICH E6 (R3) Good Clinical Practice (GCP) principles, alongside new guidance on quality, risk proportionality, and clinical investigations.

The guidance Clinical trials for medicines: Compliance with ICH E6 Good Clinical Practice (GCP) in the United Kingdom, Clinical trials for medicines: guidance on quality and risk proportionality, and Clinical investigations for medical devices (updated April 2026) together provide a comprehensive regulatory framework for both medicinal and medical device trials.

Guidance 1: Compliance with ICH E6 Good Clinical Practice (GCP) in the United Kingdom

Introduction

This guidance explains how ICH E6 (R3) Good Clinical Practice principles are implemented and enforced within UK clinical trial legislation. It ensures that all trials involving investigational medicinal products are conducted according to internationally recognised standards of ethics, safety, and scientific quality. This guidance applies to all stakeholders involved in UK clinical trials, including sponsors, investigators, and service providers. It covers compliance throughout the entire trial lifecycle, from design and conduct to reporting and inspection.

Training in GCP

All personnel involved in clinical trials must receive appropriate GCP training, which should be proportionate to their roles and responsibilities. Training must be documented, and organisations are encouraged to use ICH-provided materials to ensure consistency.

United Kingdom-Specific GCP Principles

While aligned with international standards, the UK retains specific legal requirements within its clinical trial regulations. These principles ensure that the broader ICH framework is applied effectively within the UK regulatory context, supported by detailed annexes for operational guidance.

Flexibility in Application

The guidance allows flexibility in applying certain aspects of ICH E6 annexes, particularly for trials not intended for marketing authorisation. This ensures that requirements are adapted without compromising participant safety or data integrity.

Guidance 2: Quality and risk proportionality

Introduction

This guidance provides detailed recommendations on applying quality by design (QbD), risk-based quality management (RBQM), and risk proportionality in UK clinical trials. It emphasizes building quality into trials from the outset rather than relying solely on retrospective checks. It applies to all UK clinical trials involving investigational medicinal products and is relevant to sponsors, investigators, and organisations responsible for trial design and conduct.

Core Principles

Quality by design ensures that critical-to-quality factors are identified early and integrated into trial design.

Risk-based quality management introduces structured processes to identify, assess, and control risks affecting participant safety and data reliability.

Risk proportionality ensures that monitoring, documentation, and oversight are tailored to the level of risk, avoiding unnecessary burden while maintaining compliance.

Practical Application

Sponsors are expected to focus on critical data and processes, rather than applying uniform controls across all aspects of a trial. Lower-risk trials may adopt simplified processes, while higher-risk trials require enhanced oversight.

Guidance 3: Clinical investigations for medical devices

Introduction

This guidance outlines the requirements for notifying the MHRA about clinical investigations of medical devices, ensuring that devices are evaluated for safety and performance before widespread use. The guidance applies to manufacturers and sponsors conducting clinical investigations of medical devices in the UK, including higher-risk and innovative products.

Notification Requirements

Sponsors must notify the MHRA of their intention to conduct a clinical investigation, typically at least 60 days before the study begins. This allows regulatory authorities to review study design and ensure compliance with safety requirements.

Regulatory Framework

Clinical investigations must comply with applicable UK medical device regulations, including requirements for:

• Study design and protocol approval

• Participant safety and informed consent

• Data collection and reporting

These investigations are critical for obtaining regulatory approvals such as UKCA marking.

Together, these three MHRA guidances establish a modern, integrated framework for clinical trials in the UK. For complete official guidance, refer to:

• Clinical trials for medicines: Compliance with ICH E6 Good Clinical Practice (GCP) in the United Kingdom – MHRA

• Clinical trials for medicines: guidance on quality and risk proportionality – MHRA

• Clinical investigations for medical devices – MHRA