On 28 April 2026, the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 came into force in the UK. The amendments make extensive changes to the UK legislative framework for clinical trials of investigational medicinal products (CTIMPs).
The changes fall into three broad categories:
- Measures that place existing processes and expectations on a statutory footing.
- Measures that align the UK more closely with aspects of the EU Clinical Trials Regulation.
- New requirements for UK clinical trials.
Earlier this year, TMC’s Head of Quality Assurance, Claire Willson, provided an overview of the new UK Clinical Trials Regulation (CTR) and what the changes mean for sponsors. This article examines the key changes in more detail.
For further practical insight into what the revised CTR framework means for sponsors, and how companies can make the most of the opportunities it creates, listen to our podcast with TMC’s Directors of Regulatory Affairs Michael Edwards and Lucy Herlihy.
Scope of the changes
The statutory instrument (SI) covers how CTIMPs are reviewed, authorised and overseen by the Medicines and Healthcare products Regulatory Agency (MHRA), the UK medicines regulator, and independent Research Ethics Committees (RECs), which provide ethical review through the UK Research Ethics Service.
CTIMPs are interventional studies involving a medicine, whether the medicine is investigational or already authorised. A CTIMP requires both MHRA authorisation and REC ethical approval before it can proceed.
The changes do not directly affect the separate approvals and permissions required for clinical trials conducted in National Health Service (NHS) settings. In England, these include Health Research Authority (HRA) approval. Scotland and Northern Ireland have equivalent arrangements through their devolved health authorities.
These separate processes consider NHS research governance and legal compliance. They are distinct from MHRA regulatory authorisation and REC ethical review. The amended clinical trials regulation framework, therefore, applies most directly to CTIMP authorisation, ethical review, conduct and reporting.
Clinical trial application and assessment
Since January 2022, sponsors have been required to submit a UK clinical trial application (CTA) through Combined Review. This is a single Integrated Research Application System (IRAS) submission that allows the MHRA and a REC to conduct regulatory and ethical assessments in parallel.
Combined Review and REC meeting arrangements remain unchanged under the new SI. However, the revised regulations now set statutory timelines after submission:
- Validation must take place within seven calendar days.
- The initial assessment period is usually 30 calendar days, provided the sponsor selects the next available REC meeting when submitting the CTA.
- The 30-day period may be extended if the MHRA and/or HRA seeks advice from a specialist committee or expert group.
Specialist advice may be needed for complex studies, including first-in-human trials, trials with novel mechanisms of action, certain immune-modulating products, advanced therapy medicinal products (ATMPs), and trials that raise significant safety concerns. Sponsors should assess whether specialist advice is likely to be needed before submitting their clinical trial application, as this may affect submission and assessment timelines.
The assessment period may also be extended where the MHRA, REC, or both raise questions. The sponsor must respond to one consolidated list of questions within 60 calendar days, replacing the previous 14-day deadline. The MHRA and REC then have up to 10 calendar days to issue a final combined decision. As before, sponsors may request an extension to the response deadline.
Notifiable trials
The MHRA has introduced a notification scheme for initial CTAs for Phase 4, post-authorisation trials and certain lower-risk Phase 3 trials.
Subject to the specified eligibility criteria, a Phase 3 trial may qualify where:
- Its protocol has already been approved in the US or EU.
- A similar trial has previously been approved in the UK.
- The investigational medicinal product (IMP) is authorised in the US, UK or EU and is used in accordance with that authorisation.
Where a clinical trial application meets the criteria, the MHRA will confirm automatic authorisation within 14 calendar days. REC review still takes place and follows the applicable statutory timeframes.
Sponsors should carefully assess eligibility before selecting this route. The notification scheme is intended to offer a more proportionate pathway for eligible lower-risk trials, while retaining REC ethical review.
Registration and trial start
The revised rules make public registration a legal requirement. A CTIMP must be registered in a publicly accessible registry by whichever occurs first:
- The date on which the first participant gives informed consent.
- 90 calendar days after approval.
Interestingly, the EU Clinical Trials Information System (CTIS) does not meet this requirement for UK trials. Unless the sponsor requests otherwise, a UK CTA is automatically registered in the ISRCTN registry. Sponsors may request a different eligible registry — for example, where the trial has been or will be registered on ClinicalTrials.gov.
Phase 1 trials may be eligible for deferred registration for up to 30 months after the trial ends. This deferral applies automatically where a Phase 1 trial involves healthy volunteers only. In either case, a minimum record must be published in a publicly accessible registry.
As under the EU CTR, CTA approval lapses if no participants are recruited within 24 months of approval. Sponsors may apply for an extension where necessary. This is one of several measures that brings the UK clinical trials regulation framework closer to the EU CTR.
Conducting and managing a CTIMP
Good Clinical Practice
From 28 April 2026, compliance with the principles of the International Council for Harmonisation (ICH) E6 Good Clinical Practice (GCP) became a legal requirement in the UK, formally incorporating ICH E6 GCP into the UK clinical trials regulation framework.
MHRA guidance notes that, where a trial is not intended to support a marketing authorization application, some aspects of the ICH E6(R3) annexes may not be relevant or may need to be interpreted in light of the trial’s circumstances.
Sponsors should, therefore, apply the updated GCP requirements in a way that reflects the nature and purpose of the study, while maintaining appropriate standards for trial conduct and data quality.
NIMPs and drug labelling
Non-investigational medicinal products (NIMPs) are now subject to statutory requirements for Good Manufacturing Practice (GMP) and drug labeling. This does not substantially change established expectations or practice; rather, it places those requirements on a statutory footing.
Where relevant, sponsors must identify NIMPs in the cover letter that accompanies the clinical trial application.
Investigational medicinal products (IMPs) manufactured after 28 April 2026 must be labeled in accordance with the revised regulations. The SI makes no substantial changes to the drug labeling requirements, although it includes minor terminology updates.
The regulations introduce a labeling exemption for point-of-care IMPs. To qualify, the IMP must be manufactured at or near the point of use and administered in full immediately after manufacture.
Sponsors may also request a variation from, or a complete exemption to, labeling requirements. For example, this may be appropriate where an IMP is an unmodified UK-authorized product, is administered solely at the clinical site, and is not handled, administered, or stored by the participant.
Safety reporting
As of 28 April 2026, sponsors must submit suspected unexpected serious adverse reaction (SUSAR) reports and development safety update reports (DSURs) for all CTIMPs to the MHRA only. This applies whether the clinical trial application was submitted through Combined Review or another route.
The updated safety reporting guidance also clarifies the procedure for urgent safety measures (USMs). Where a sponsor takes a USM, it must:
- Notify the MHRA as soon as possible and no later than three calendar days after taking the measure.
- Submit written notification within seven calendar days.
- Submit a substantial modification covering only the USM within two weeks of the initial notification, subject to MHRA agreement that the measure qualifies as a USM.
Managing modifications
The regulations now use the term “modification” rather than “amendment”, bringing UK terminology closer to that used in the EU Clinical Trials Regulation.
Sponsors must classify each proposed modification as one of the following:
- Minor modification: does not require approval and may be implemented immediately.
- Modification of an important detail: does not require approval but must be notified for information. This is broadly comparable to Article 81(9) of the EU CTR.
- Substantial modification: requires approval before implementation and must follow either Route A or Route B.
An updated IRAS amendment tool supports the classification process, while MHRA guidance provides examples of changes within each category. For instance, the date the first participant is recruited in the UK must be notified as a modification of an important detail.
A Route A substantial modification receives a full assessment. The target assessment period is 35 calendar days from validation. If further information is requested, the sponsor has up to 60 calendar days to respond, after which a decision is issued within 10 calendar days.
Route B offers an accelerated pathway. It may apply where the same modification has been approved in the US or EU, or where the modification involves an eligible specified change to the protocol, investigator’s brochure (IB) or summary of product characteristics (SmPC).
For an eligible Route B modification, the MHRA will issue automatic approval within 14 calendar days. If it does not meet the Route B eligibility criteria, it must be assessed through Route A. REC approval remains necessary where relevant, and sponsors must not implement a modification requiring REC review before that approval is granted.
Transitional arrangements
CTAs authorised before 28 April 2026 are subject to transitional arrangements. The exact requirements depend on the activity concerned.
However, any modification submitted on or after 28 April 2026 is governed by the revised rules, regardless of when the original CTA was authorised. This means sponsors must use the new modification categories and routes when making changes to existing trials.
Transparency and reporting results
The amended clinical trials regulation framework introduces a legal requirement for sponsors to offer participants an accessible, lay summary of trial results within 12 months of the end of the study. A deferral or waiver may apply where agreed with the HRA.
Sponsors must also publish a summary of results in the same public registry used to register the trial. However, directing participants to the registry does not fulfil the separate obligation to offer them a lay summary.
These transparency requirements apply to all CTIMPs with an end date on or after 28 April 2026, regardless of when the CTA was originally submitted or approved.
For CTAs submitted before 28 April 2026, sponsors are recommended — though not legally required — to offer participants an accessible summary of results. These trials must be registered in a public registry by whichever occurs first:
- 90 calendar days from 28 April 2026.
- The date of first informed consent, where this occurs after 28 April 2026 but before the end of the 90-day period.
New CTAs must include information on how the sponsor intends to share results. Detailed HRA guidance is available on the transparency requirements.
Navigating the updated UK CTR requirements
The amended UK clinical trials regulation framework makes substantial changes to CTIMP authorisation, conduct, maintenance and reporting.
Several provisions formalise practices that sponsors already follow. However, for organisations new to UK research, the updated requirements can be complex to interpret and apply.
The notification scheme for eligible lower-risk trials, Route B for qualifying substantial modifications, statutory registration requirements and strengthened transparency obligations are among the most significant developments for UK sponsors.
TMC’s regulatory and clinical experts can support sponsors with trial strategy, regulatory submissions, maintenance and compliance planning — helping drug development programmes progress efficiently and bring medicines to patients in the UK, EU and beyond. Speak to our team today for further advice and support.