This statutory instrument amends the Medicines for Human Use (Clinical Trials) Regulations 2004 (2004 No.1031). The legislation aims to protect public health and trial participants while supporting the development of new and improved medicines. It seeks to remove barriers to innovation through proportionate, risk-based approaches; to streamline clinical trial processes and maintain strong oversight of safety. It also enables sponsors to run trials across countries, helping to ensure the UK remains a preferred location for multi-national clinical research. This document sets out mandatory legal requirements for the conduct of clinical trials in the UK. The regulation comes into force on 28 Apr 2026. The regulation updates effect researchers, sponsors, research ethics committees, trial participants, the public and healthcare professionals. Researchers and sponsors should already be reviewing which processes, systems, and procedures require updates, and ensuring staff are trained accordingly, in addition to understanding the legislation itself. The Medicines and Healthcare products Regulatory Agency (MHRA) and the Health Research Authority (HRA) have each published guidance to support researchers and sponsors in preparing for the implementation of the regulation.
Key Considerations
New definitions have been introduced:
Non-Investigational Medicinal Product – A medicinal product used or to be used in a clinical trial, as described in the protocol, but not as an investigational medicinal product.
Public Registry – A primary or partner registry of, or a data provider to, the World Health Organization (WHO) International Clinical Trials Registry Platform, provided that the registry, or the data provider, facilitates public access to information about the trial in the UK.
Notifiable Trial – A trial where there are no significant safety concerns with any of the investigational medicinal products, as far as the sponsor is aware having made reasonable enquiries. The provision applies to clinical trials that meet one of three specified conditions (A, B, or C) and exclude higher-risk participants or products. Specifically, the trial must not involve children, pregnant or breastfeeding participants, advanced therapy medicinal products, or medicines being used for the first time in humans.
The trial qualifies if any one of the following is true:
Condition A: The investigational product is already authorised in the UK and is used either in line with that authorisation or supported by established clinical practice.
Condition B: A similar trial using the same product was approved in the UK within the past two years, at the same or higher dose, frequency, and duration, using the same manufacturing process, route of administration, and indication.
Condition C: The trial has been assessed and approved by the relevant clinical trials authority in the EU, an EEA state, or the US.
Updated terminology has been implemented:
A ‘trial site’ is now referred to as a ‘trial location’. This is to better portray that this term refers to anywhere that is conducting a clinical trial which includes the analysis or evaluation of human samples collected as part of the clinical trial. The term ‘authorised health care professional’ has been removed. The guideline instead states that investigators should be health care professionals. ‘Subjects’ are now referred to as ‘participants’ to align with the ICH E6 R3 guideline. ‘Amendments’ are now referred to as ‘modifications’ to align with the ICH E6 R3 guideline.
Modifications:
Modification of an Important Detail – A change that regulators need to be informed about for oversight or administrative purposes but that does not significantly affect participant safety or rights.
Modification to a Clinical Trial Approval – Any change to the approval request itself or to the associated applications, documents, or ethics submissions.
Route A Substantial Modification – A change that is likely to have a significant impact on participant safety or rights, or on the reliability or robustness of the trial data.
Route B Substantial Modification – A change to an approved clinical trial where the sponsor is not aware of any new significant safety concerns and the modification meets one of three conditions.
The modification qualifies if any one of the following applies:
Condition A: The change has already been reviewed and approved by a recognised overseas regulator (EU, EEA, or US), does not involve a first-in-human product, and the submitted documents are identical to those reviewed overseas and contain no UK-specific content.
Condition B: The change is limited to specified protocol amendments, such as changes to trial objectives, endpoints, design or statistical considerations, end-of-trial criteria, permitted medications, participant safety assessment schedules (where no new safety concern exists), or UK-specific adaptations to a global protocol that do not alter safety reporting requirements.
Condition C: The change is limited to updates to the investigator’s brochure or summary of product characteristics, such as adding new toxicological or pharmacological data, updating reference safety information, or making non-substantive brochure updates, provided there is no change to the approved risk-benefit assessment, safety profile, or trial protocol due to safety concerns
The sponsor must document their determination of whether a modification meets the criteria for a Route A or Route B substantial modification.
Approval Process:
Clinical trial approval and any subsequent modifications are submitted as a single application to both the MHRA and HRA. The review process has a maximum 60-day turnaround, including up to 30 days to issue the initial outcome and any request for further information (RFI), up to 14 days for the applicant to respond to the RFI, and up to 16 days for the final outcome to be issued. Sponsors are required to recruit the first participant within two years of clinical trial approval in the UK; otherwise, the approval will lapse
Simplified Arrangements for Consent:
When the investigational medicinal product, or each product if there is more than one, is authorised for use in the UK and used according to that authorisation, is administered to the participant as part of their routine health care, and the participant receives no additional medication or undergoes no extra interventions or diagnostic procedures solely for the purposes of the trial; simplified consenting arrangements can be used. The clinical trial protocol may include simplified arrangements for obtaining and documenting consent. These arrangements must specify the reason for using simplified consent, the information to be provided to the participant and how it will be delivered, and the method by which consent will be evidenced.
GCP and the Conduct of Clinical Trials:
- If conducting a clinical trial in the UK, in order to claim GCP compliance, it is a legal requirement to follow ICH E6 R3
- It is a requirement for sponsors to oversee development and maintenance of computerised systems, which could lead to an increase in audit activities
- It is a requirement for sponsors to select and oversee laboratories, which could lead to an increase in audit activities
- Clinical trials must be registered in the public registry prior to first patient recruited or within 90 days of approval, which ever in sooner
- A summary of the results of the clinical trial must be published within 12 months of the end of the trial
- Clinically significant abnormal laboratory findings are considered adverse events
- Certain abnormal laboratory parameters should be specified in the protocol as requiring reporting to the sponsor within 24 hours
- Investigational medicinal product labels are required to include the wording ‘for clinical trial use only’ and information which identifies the product, the participant, the clinical trial and the sponsor
- The 5 year retention period of clinical trial data has been updated to 25 years, in line with the EU
- Written notification for urgent safety measures sent to the MHRA and ethics committee immediately: the allowed period has been increased from no later than 3 days to no later than 7 days, with the expectation remaining as soon as possible
