Perspectives

Updated UK Clinical Trial Regulation: The Key Changes and Impact on Development Safety Update Report (DSUR) Requirements

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently announced the most significant overhaul of the UK clinical trials regulations in two decades.¹ This reform promises to accelerate and streamline the clinical trial approval process, helping to position the UK as a top destination for safe and innovative clinical research.

In this article, we’ll focus on the key changes introduced by the revised UK Clinical Trials Regulation (UK CTR) that may impact on the Development Safety Update Report (DSUR) requirements.

What is the UK Clinical Trials Regulation (UK CTR)?

The original Medicines for Human Use (Clinical Trials) Regulations 2004,² came into effect more than 20 years ago, transposing the EU Clinical Trials Directive 2001/20/EC into UK law. Since then, this regulation has been the cornerstone of clinical trial governance in the UK, focusing on protecting the rights and safety of participants while ensuring the research process is streamlined and compliant.

The MHRA has collaborated with the Health Research Authority (HRA) and the Department of Health in Northern Ireland to carefully consider over 2,000 responses from global stakeholders through the public consultation on proposals for legislative changes.³^,⁴

The updated UK CTR⁵ was laid before the UK Parliament on December 12, 2024, with a planned implementation in early 2026 following a 12-month transition period.³

What Are the Key Changes for DSURs?

The full details of how the aforementioned changes will affect DSURs are still being finalized, but two of the main items relevant to these reports are as follows:

1. Removal of SAE and SAR Listings from DSURs
One of the most notable changes in the updated UK CTR is the proposal to remove the obligation for including listings of serious adverse events (SAEs) and serious adverse reactions (SARs) in DSURs. Instead, Sponsors will be expected to provide a relevant discussion of the signals and risks associated with the medicinal product, along with proposed risk mitigation strategies.^4,5,6

Sponsors are likely already familiar with this approach as it aligns with the 2021 guidance issued jointly by the MHRA and Health Canada⁷^,⁸, and it mirrors practices already established in the EU.⁹

Flexibility for Sponsors: Sponsors will still have the option to include SAE and SAR listings in their DSURs if desired,⁴^,⁵ particularly when preparing global reports. However, those focusing on the UK may find the reduced requirement a more efficient approach. The MHRA may still request SAE and SAR listings if additional investigation into specific safety concerns is needed, giving Sponsors 30 days (or a shorter period, as specified) to provide the data.⁵

2. Exemption from Submitting DSURs to Research Ethics Committees (RECs)
Another proposed change in the revised UK CTR is the elimination from the requirement to submit DSURs to Research Ethics Committees (RECs).⁶ Under the new legislation, the MHRA will assume responsibility for assessing DSURs, coordinating with RECs as necessary.⁴

Clarifying Roles: This new measure seeks to streamline the review process by distinguishing the specific roles of the MHRA and RECs. The MHRA will focus on monitoring ongoing safety data, while RECs will continue their oversight on the ethical aspects of the trial to ensure participant well‑being.⁴

Benefits for Sponsors: At present, Sponsors are often required to submit the same safety data to both the MHRA and RECs, resulting in unnecessary duplication. By removing this dual reporting requirement, Sponsors can reduce administrative burdens and enhance efficiency, all while maintaining the highest standards of participant safety.

How to Prepare for the Transition and Next Steps

As the updated UK CTR moves through the legislative process, the MHRA and HRA will work together to develop detailed guidance to support its implementation.¹^,³ Given the expected changes, it’s essential for Sponsors to stay current with the evolving regulatory landscape.

Three ways for Sponsors to prepare are as follows:

Monitor updates from the MHRA and HRA throughout the transition period.
Review current DSUR processes and evaluate how the changes may affect your submissions.
Ensure your team are prepared to adapt to the new DSUR requirements once they are finalized and effective.

Staying informed and being proactive will be key in ensuring compliance with the updated framework and minimizing disruptions to clinical trial operations.

MMS experts are on stand-by to answer any questions related to the content in this article. To be connected with an expert in DSURs or other periodic aggregate safety reports (such as PBRERs and PADERs), email info@mmsholdings.com and we’ll connect you with the right person.

With a strong foothold in the UK and Europe, MMS routinely helps sponsors succeed in building regulatory submissions across all major global health authorities. For details on how MMS helps EU companies gain new drug approval in the US, read this article next.