MHRA Clinical Trials Reform: Practical Steps for Sponsors

The UK is entering the implementation phase of the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025, with the bulk of the operational changes taking effect on 28 April 2026.

In practice, sponsors must plan across two regimes in 2026, with new guidance that separates the “old rules” from “new rules” and prepares sponsors for the requirements of the new regulation.

Alongside the procedural changes, the MHRA and the HRA have refreshed the clinical trials guidance library to clarify expectations on documentation, validation, safety reporting, labelling, archiving, and trials that include devices, while also signposting the UK’s new annex to ICH E6(R3) Good Clinical Practice, containing UK‑specific annotations.

Sponsors that adopt this guidance early can shorten study start‑up timelines, minimise regulatory delays, and maintain strong compliance throughout the clinical trial lifecycle. The MHRA also provides transitional guidance to help sponsors enhance and maintain consistent inspection‑readiness where needed.

Why does the change in regulation matter for Sponsors?

The regulatory intent for the regulation update is simple. The UK wants a streamlined, more predictable approvals pathway, greater transparency and a modernised GCP baseline that supports innovative design, without compromising participant safety.

For sponsors, this translates into a more streamlined approach to clinical trial applications for both notifiable and non-notifiable trials, more predictable timelines, wider use of combined review, and clearer risk-proportionate controls, especially for lower-risk trials and modifications.

Old rules to new rules: transitional arrangements you need to action

From 28 April 2026, any clinical trial application (initial or substantial modification) that is submitted is applicable as a “new rules” clinical trial. Applications submitted before that date can remain under the old rules, even if the decision arrives after go-live. The MHRA’s transitional guidance details how this status affects approvals, modifications, pharmacovigilance, IMP manufacture and import, labelling, and enforcement. Sponsors should map their pipeline to these cut-offs now and decide which studies to advance under which regime. To note, new clinical trials have greater transparency requirements, so it is important to understand reporting obligations for these new trials.

Practical Steps

• Build a portfolio-level transition plan indicating rule status, planned clinical trial application submission dates, transparency requirements, and whether modifications are likely to fall under old or new provisions.
• Ensure Sponsors are up to date on the updated definitions applicable to new and ongoing clinical trials.
• Confirm whether upcoming studies or modifications qualify for the notification-based fast-track routes or accelerated phase 1 timelines provided by regulators as part of the regulation reform context.

Documentation and validation: getting the combined review right

IRAS submission for combined review remains the default route for new CTIMPs and combined IMP-device trials. The HRA’s step-by-step guidance and document management tables clarify exactly which content is mandatory for verification and which body receives it. A new pathway for submissions is also being released, called a notifiable trial for studies where there are no significant safety concerns. It is therefore pertinent that Sponsors thoroughly read the guidance to ensure they apply through the correct pathway. It should be confirmed whether the accelerated MHRA approval through the notifiable trial category is applicable for upcoming studies.

Practical steps

• Use the HRA’s document mapping table to pre-check completeness, and align cover letters to MHRA’s expectations for CTAs, RFIs and DSURs.
• Determine which pathway is most appropriate to submit the clinical trial application for authorisation.
• For studies involving ionising radiation or investigational medical devices, follow the HRA’s interim instructions to avoid validation delays.

Substantial amendments: how to amend ongoing trials

The MHRA are providing additional routes and terminology to modify trials. Notably, the term ‘amendments’ is being changed to ‘modifications,’ aligning with the EU. Modifications to trials will fall under 1 of the following 3 categories: Substantial Modification (Route A or Route B [accelerated MHRA approval]), Modification of an Important Detail, or a Minor Modification. Each category has different reporting requirements, including notification timelines and implementation requirements, so it is important to understand which one is most appropriate for upcoming modifications. If you submit under the incorrect pathway, the MHRA has said they may invalidate the modification and that it will need to be resubmitted under the correct pathway.

Practical steps

• Read the guidance to understand which pathway is applicable for upcoming modifications, and if accelerated approvals are applicable.
• Map timelines to understand the expected validation and approval dates to ensure there are no delays post-approval.

Labelling: what changes and how to plan for it

MHRA’s clinical trials labelling guidance has been updated to cover the amended Regulations. This includes IMP and non-IMP routes for approval of labels, and when labelling requirements can be varied or disapplied. Sponsors should update master label sets, QMS references, and change controls ahead of April 2026 to avoid questions from the MHRA after implementation of the Regulation. Our recent LinkedIn post outlines some important updates within the clinical trial labels.

Practical steps

• Conduct a label content gap check against the updated MHRA guidance and ensure your labels are compliant according to the regulation. This should include proactive planning to update any currently approved trial labels with the next substantial modification.

Safety reporting and annual safety updates: raise the bar on readiness

MHRA has published consolidated safety events guidance that sets out definitions, MedDRA coding, SUSAR expectations, urgent safety measures, and annual reporting. Included within this are updates to the submission timelines and procedures for suspected unexpected serious adverse reactions (SUSARs) and urgent safety measures (USMs).

Therefore, it is essential for Sponsors to adapt to ensure compliance with the regulation, although the majority of the safety reporting changes involve relaxing procedural burdens rather than tightening them. Annual safety reports (ASRs/DSURs) have also had their content and timeline requirements put into legislation, although this is unlikely to be different to current ongoing procedures. Sponsors should embed these submission routes and timelines in their QMS.

Practical steps

• Align USM, SUSAR, and ASR procedures with the HRA’s combined review pathways to ensure the correct channel is used and timelines are met.

Archiving and retention: align with the UK’s GCP-inflected position

Draft MHRA guidance on archiving and retention of clinical trial records recognises the ICH E6(R3) definition of essential records and clarifies retention expectations and TMF responsibilities under the amended Regulations. Sponsors should revisit TMF plans, digital archiving controls and vendor arrangements, particularly where mixed paper and electronic records exist. Under the UK CTR-2025, the MHRA introduce the possibility to suspend or terminate a part of a clinical trial, in addition to the whole trial, so steps should be taken to ensure sufficient documentation is filed within the correct timelines accordingly.

Practical steps

• Refresh your TMF and site file retention matrices using ICH E6(R3) Appendix C as the anchor, and document any extended retention linked to marketing authorisation plans.

Trials that include devices or IVDs: know when extra submissions apply

Where a CTIMP includes an in vitro diagnostic device used for patient management decisions in Great Britain, the MHRA requires additional information at CTA, with a published workflow for applications to follow. Pure medical device clinical investigations remain notifiable under the device’s framework, while the MHRA updated its guidance and manufacturer handbook in 2025. Combined IMP-device trials continue through the combined review.

Practical steps

• For CTIMPs with an IVD, preassemble device technical documentation, conformity status and exemption rationale where applicable, and mirror this in IRAS.
• For device-only investigations, verify whether a 60-day notification is required and check the latest UK-specific guidance and flowcharts.

Trial procedures – GCP in the UK: ICH E6(R3) with UK-specific annotations

The UK continues to follow the ICH E6(R3) Good Clinical Practice; however, they are now supported by UK-specific annotations that explain how the principles interact with the amended Clinical Trials Regulations through a separate annex (Annex 1).

This reinforces a risk-proportionate, quality-by-design approach, clarifies medical oversight responsibilities, and strengthens data governance. Sponsors should train teams on the UK annotations and update quality systems where necessary.

The clinical trial regulation also introduces the possibility for simplified informed consent form requirements for trials with approved drug products that are taken according to their marketing authorisation and non-interventional trials.

Practical steps

• Build a concise site-facing guide on the impact of the recent updates to ICH E6(R3) and the impacts of the changes locally, including proportionality, critical-to-quality factors and data governance expectations.
• Determine whether any new or ongoing studies are applicable for simplified consent forms.

Top recommendations for preparation between now and April 2026

• A transition plan per study, mapping old rules versus new rules status, with target submission dates and modification strategies for new and ongoing trials.
• IRAS-ready documentation, validated against HRA checklists, with device or radiation specifics addressed upfront.
• Safety reporting QMS updates that meet the updated safety reporting requirements.
• Updated label sets and change controls aligned to MHRA labelling guidance.
• GCP training and QMS updates reflecting ICH E6(R3) and UK annotations, including data governance and proportionality.
• Device and IVD pathways are pre-assessed, with combined review packages prepared where appropriate.

Conclusion

The UK’s clinical trial reforms are intended to make the UK a more attractive location for global clinical trials. They are providing guidance to create a faster, clearer and more streamlined clinical trial approval process. These updates also require deliberate action for sponsors with ongoing trials, so Sponsors need to be transitioning, maintaining a high standard of documentation quality, and updating safety governance, labelling, archiving, and device-related pathways for their new and ongoing trials.

The adoption of ICH E6(R3), with UK-specific annotations, sets a modern GCP baseline that rewards quality-by-design and risk-appropriate oversight.

Sponsors that operationalise these changes now will enter 2026 with fewer delays and stronger inspection readiness.

How DLRC can help

DLRC supports sponsors with a UK-ready clinical trials strategy, from combined review preparation and validation troubleshooting to document reviews and device-inclusive trial pathways. DLRC can also support if you have global clinical trials and want to expand into the UK. If you would like a gap analysis or independent readiness review focused on April 2026 implementation, our team would be pleased to help. Contact us at hello@dlrcgroup.com.

This article reflects DLRC’s interpretation of the UK clinical trials reforms and publicly available guidance