MHRA Updates Comprehensive Guidance Framework for Clinical Trials in the UK (October 2025)

Sharan Murugan
Oct 5
3 min read

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has issued a coordinated update to its suite of clinical trial guidances on 1 October 2025, reflecting the UK’s transition to an independent regulatory system post-Brexit. This collective update covers key areas such as authorisation, approvals, labelling, safety reporting, amendments, and transitional provisions, ensuring harmonisation with the UK Clinical Trials Regulations 2022 and alignment with global best practices.

1. Apply for Authorisation of a Clinical Trial in the UK

This guidance outlines how sponsors must apply for MHRA authorisation before initiating a Clinical Trial of an Investigational Medicinal Product (CTIMP).

Key Highlights:

Applications must be made via the Integrated Research Application System (IRAS).
Documentation includes the investigator’s brochure, clinical trial protocol, and risk assessments.
The MHRA review period is generally 30 days, with potential requests for clarification or additional information.
Combined review with Research Ethics Committees (RECs) is available for streamlined assessment.

2. Transitional Arrangements for Clinical Trials

This guidance explains how ongoing trials approved under EU directives can transition to compliance with UK-specific regulations.

Key Points:

Existing EU CTR trials must transition by 2026 to the UK framework.
Sponsors must submit updated documentation aligning with UK formats.
MHRA provides a simplified pathway to maintain continuity of multinational studies.

3. Apply for Approval of a Clinical Trial

This guidance details when approval (distinct from authorisation) is required—specifically for ethics and institutional oversight.

Highlights:

Focus on ethical review through Health Research Authority (HRA) and Health and Care Research Wales (HCRW).
Requirements for informed consent, patient data protection, and trial site suitability.
Guidance on multi-site and cross-border trials within the UK nations.

4. Notifiable Clinical Trials

This guidance defines which studies qualify as notifiable to the MHRA.

Examples include:

Trials using unauthorised investigational medicinal products (IMPs).
Trials comparing different dosing regimens or formulations.
Device-drug combination products.

Non-notifiable trials, such as those involving marketed products within normal use, do not require MHRA notification.

5. Labelling of Investigational Medicinal Products (IMPs)

This guidance prescribes labelling standards for IMPs, ensuring traceability, subject safety, and regulatory compliance.

Requirements Include:

Product name, strength, batch number, and expiry date.
Storage conditions and unique trial identifiers.
Clear statement: “For clinical trial use only”.
English-language labelling mandatory across all UK sites.

6. Collection, Verification, and Reporting of Safety Events

This guidance provides a comprehensive framework for pharmacovigilance during clinical trials.

Key Points:

Sponsors must record and report Suspected Unexpected Serious Adverse Reactions (SUSARs) within 7–15 days.
Annual safety reports (DSURs) required for all ongoing trials.
Emphasis on data integrity and prompt communication with MHRA.

7. Ending a Clinical Trial

This guidance explains procedures for terminating or temporarily halting a study.

Highlights:

Notification to MHRA required within 15 days of early termination.
Final clinical study report must be submitted within 12 months.
Additional provisions for safety-related halts with expedited notification timelines.

8. Expert Advice for Clinical Trials

This guidance outlines MHRA’s service allowing sponsors to seek scientific or regulatory advice prior to submission.

Features:

Formal meetings for protocol design and regulatory strategy.
Tailored support for innovative therapies, ATMPs, and rare diseases.
Integration with Innovative Licensing and Access Pathway (ILAP) for accelerated development.

9. Modifying an Approved Clinical Trial

This guidance covers how to amend a trial after initial approval.

Includes:

Substantial amendments (e.g., protocol changes, investigator updates).
Non-substantial amendments (e.g., administrative or logistical updates).
IRAS submission process and timelines for MHRA acknowledgment or approval.

10. Clinical Investigations for Medical Devices

This guidance specifies requirements for medical device investigations in the UK.

Focus Areas:

Pre-market and performance studies.
Notification at least 60 days before study start.
Parallel ethics approval through HRA.
Fees and documentation requirements for sponsors.

11. Clinical Trials Involving In Vitro Diagnostic (IVD) Devices

This guidance defines how IVD devices used in drug trials should be managed.

Examples:

Diagnostic assays used for patient eligibility.
Companion diagnostics co-developed with medicines.
Documentation and safety verification required as per the UK Medical Devices Regulations 2002.

12. Non-Investigational Medicinal Products (NIMPs)

This guidance clarifies how NIMPs—medicines used within a trial but not under investigation—should be controlled.

Includes:

Rescue medications, challenge agents, or background therapies.
Manufacturing, labelling, and import requirements.
Pharmacovigilance obligations remain consistent with IMPs.

The updated October 2025 MHRA guidance suite provides an integrated, transparent framework for the conduct, oversight, and reporting of clinical trials in the UK. By harmonising the entire lifecycle—from authorisation to termination—these updates enhance regulatory clarity, support innovation, and uphold patient safety, positioning the UK as a global leader in ethical, efficient, and science-driven clinical research.