UK MHRA Guidance: Collection, Verification, and Reporting of Safety Events and Clinical Trials Regulations Transitional Arrangements

The UK clinical trials regulatory framework has undergone significant changes following amendments to the Medicines for Human Use (Clinical Trials) Regulations. These changes introduce updated requirements across clinical trial conduct, safety reporting, transparency, Good Clinical Practice (GCP), investigational medicinal products, and regulatory oversight.

To support sponsors and investigators, the Medicines and Healthcare products Regulatory Agency (MHRA) has published updated guidance covering two important areas: Collection, Verification and Reporting of Safety Events and Clinical Trials Regulations Transitional Arrangements.

Together, these guidances help stakeholders manage clinical trial safety obligations while transitioning from the previous regulatory framework to the amended Clinical Trials Regulations, which took full effect on 28 April 2026.

Guidance: Collection, Verification and Reporting of Safety Events 

Safety monitoring is a fundamental responsibility throughout the conduct of a clinical trial. Sponsors and investigators must have appropriate systems to identify, assess, document, and report safety information to continuously evaluate the benefit-risk balance of an investigational medicinal product (IMP).

The guidance outlines requirements and recommendations covering adverse events, serious adverse events, Reference Safety Information (RSI), suspected unexpected serious adverse reactions (SUSARs), annual safety reporting, urgent safety measures, serious breaches, and temporary trial suspensions.

Adverse Events and Serious Adverse Events

Investigators are responsible for identifying and reporting safety events during clinical trials. Serious adverse events (SAEs) must generally be reported immediately to the sponsor, except where the protocol or Investigator's Brochure specifies otherwise. Immediate reporting should occur within a very short period and should not exceed 24 hours after the investigator becomes aware of the SAE.

Sponsors are responsible for maintaining systems for safety data collection, validation, evaluation, follow-up, reporting, and archiving while continuously assessing the trial's benefit-risk balance.

MedDRA Coding and Safety Assessment

The guidance recommends using the Medical Dictionary for Regulatory Activities (MedDRA) to support consistent coding of safety information. For SUSAR reporting and Development Safety Update Reports (DSURs), safety events should be coded using appropriate MedDRA Preferred Terms.

The assessment of safety events considers three important elements: seriousness, causality, and expectedness. The investigator generally assesses seriousness and causality, while the sponsor typically determines expectedness based on the applicable Reference Safety Information.

Reference Safety Information

The Reference Safety Information (RSI) plays a central role in determining whether a suspected serious adverse reaction is expected or unexpected.

The RSI should contain clearly identified expected serious adverse reactions and their frequencies using MedDRA Preferred Terms. Sponsors should ensure that the appropriate RSI is available for each IMP, including comparator products where applicable, and that its location is clearly identified within the clinical trial documentation.

SUSARs and Annual Safety Reporting

Sponsors are responsible for identifying and reporting Suspected Unexpected Serious Adverse Reactions (SUSARs) to the licensing authority in accordance with applicable regulatory timelines.

Sponsors must also maintain ongoing safety oversight and provide annual safety reports, including Development Safety Update Reports (DSURs), to support continued assessment of the investigational product's safety profile and overall benefit-risk balance.

Urgent Safety Measures, Serious Breaches and Trial Suspension

Where an immediate risk to participant safety is identified, sponsors and investigators may need to implement urgent safety measures before obtaining prior regulatory approval.

The guidance also addresses the reporting and management of serious breaches that could significantly affect participant safety, rights, or the reliability and robustness of trial data.

Where safety concerns require trial activities to be temporarily suspended, sponsors should follow the applicable regulatory processes while ensuring appropriate communication with the relevant authorities and protection of trial participants.

Guidance: Clinical Trials Regulations Transitional Arrangements. 

The transition to the amended UK Clinical Trials Regulations requires sponsors to understand whether their clinical trials continue under the previous requirements or become subject to the new regulatory framework.

This guidance explains how the transition affects clinical trial applications, transparency, modifications, Good Clinical Practice, pharmacovigilance, manufacturing and importation, IMP labelling, and regulatory enforcement.

Old Rules and New Rules Clinical Trials

The transitional framework distinguishes between "old rules clinical trials" and "new rules clinical trials." The regulatory requirements that apply to an individual trial depend on factors including when the clinical trial application was submitted and approved in relation to the implementation of the amended Clinical Trials Regulations. Sponsors should therefore determine the regulatory status of each trial to understand which requirements apply throughout its lifecycle.

Clinical Trial Applications and Modifications

The guidance establishes transitional arrangements for clinical trial approval applications submitted around the implementation of the new Regulations. It also explains how sponsors should manage applications for modifications during the transition period. Depending on the status of the trial, different requirements may apply when submitting changes to previously approved clinical trial documentation or conduct.

Transparency Requirements

The amended regulatory framework introduces updated clinical trial transparency requirements. Transitional arrangements determine how these obligations apply to ongoing and newly approved trials.

Sponsors should evaluate the status of each clinical trial to determine applicable requirements for trial registration, publication of results, and communication of trial information.

Good Clinical Practice and Pharmacovigilance

The transitional guidance addresses how updated Good Clinical Practice requirements apply to clinical trials during the transition. It also provides arrangements for pharmacovigilance obligations, helping sponsors determine the applicable requirements for safety monitoring and reporting as trials move between the previous and amended regulatory frameworks.

Manufacturing, Importation and IMP Labelling

Transitional provisions also apply to the manufacture and importation of investigational medicinal products.

Sponsors and manufacturers should assess whether existing IMP supplies and manufacturing arrangements remain compliant and determine when updated regulatory requirements become applicable.

The guidance similarly addresses transitional arrangements for IMP labelling to help sponsors manage existing and newly manufactured clinical trial supplies during implementation of the new Regulations.

Enforcement During the Transition

The MHRA retains regulatory oversight and enforcement responsibilities throughout the transition period. Sponsors, investigators, manufacturers, and other stakeholders should understand which regulatory provisions apply to individual trials and maintain appropriate documentation demonstrating compliance.

Effective transition planning is therefore important to avoid regulatory gaps and ensure that ongoing clinical trials continue without unnecessary disruption.

References

• Collection, Verification and Reporting of Safety Events 

  Published: 25 June 2025 | Last Updated: 15 July 2026

• Clinical Trials Regulations Transitional Arrangements. 

  Published: 25 June 2025 | Last Updated: 15 July 2026