Upcoming changes to CTIMP regulations

From 28 April 2026, new UK CTIMP regulations and updated GCP standards (amendment 2025/528, ICH E6 R3) take effect. All researchers and sponsors must ensure compliance.

On 28 April 2026, new regulations (amendment 2025/528 and ICH E6 R3) will come into effect for Clinical Trials of Investigational Medicinal Products (CTIMPs) in the UK.

The changes aim to modernise and streamline the running of clinical trials.

As a result of the changes, everyone involved in research – including investigators and sponsors – will need to work in accordance with the new regulations. The JRO is committed to supporting the transition to the new regulations.

This web page summarises key changes and what they mean for the JRO and investigators.

The JRO will be on hand to support investigators during the transition to the new regulations.

For any questions, please contact: ctimps@ucl.ac.uk.

Actions for Investigators and the JRO

The GCP training provided by the JRO has already been updated to include the latest ICH E6(R3) guidelines. If you have not completed GCP training in the past two years, please visit the JRO Eventbrite page for upcoming sessions.

UCL sponsored JRO managed CTIMPS:

As a result of the changes, the JRO will be revising all existing CTIMP Standard Operating Procedures (SOPs), templates and documents (e.g. protocols, consent forms, monitoring plans) to align with the new regulations and ICH E6(R3) by April 2026.

For more details, please contact ctimps@ucl.ac.uk

For UCL-sponsored CTIMPs managed by the JRO, which already have approval under the existing regulations, the JRO will apply updates to be compliant under the new framework, including required modifications or administrative changes.

Actions for investigators and study teams for Hosted CTIMPs:

We ask all investigators and study teams to:

familiarise yourself with the changes summarised below
Review your current CTIMP protocols, monitoring plans, data management plans, safety reporting procedures, and see where updates may be needed to align with risk-based approaches, enhanced oversight and documentation expectations and discuss with the study sponsor
Plan for updating your systems, processes and documentation ahead of April 2026 (e.g. consent processes, registry submissions, record-keeping systems)
Monitor forthcoming HRA/MHRA guidance (on interpretation, templates, FAQs) and attend training
For any new CTIMP applications submitted before April 2026, continue to follow the 2004 Regulations, but prepare to transition when new regulations come into effect.
Ensure you have received updated training in ICH E6(R3)

Engage early with the JRO if you anticipate complications or need help in assessing what changes are required in your study, uclh.randd@nhs.net

Key dates and scope

The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 were signed into law in April 2025, triggering a 12-month implementation period, with the new regulations coming into effect on 28 April 2026.
Until 28 April 2026, CTIMPs should continue to be conducted under the existing Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031).
The MHRA has confirmed that ICH E6(R3) will be implemented at the same time as the above regulatory changes (28 April 2026).

Key changes

Terminology and definitions

The term ‘amendment’ will be replaced by ‘modification’, and modifications will be categorised into:
- substantial modification
- modification of an important detail or
- minor modification.
New definitions introduced include:
- ‘non-investigational medicinal product (non-IMPs)’
- ‘notifiable trial’ and
- ‘public registry’
Some existing terms will be changed:
- ‘subject’ will be replaced with ‘participant’
- ‘trial site’ will be replaced with ‘trial location’
The new regulations will broaden the definition of a 'health care professional', in relation to (CTIMPs). The new health care professional definition will apply to both chief investigators and investigators, so that a broader group of healthcare professionals can take on the role.

Review and approval processes

The Combined Review process (one application covering both ethics and regulatory review) will now be the only way of seeking approval for CTIMPs
The adoption of a more risk-proportionate approach to clinical trials will depend on the level of risk. The legislation now includes the concept of a ‘notifiable trial’ whereby the MHRA may choose to approve the request for such a trial without further assessment.
For modifications, trial changes are categorised by risk:
- Route A for higher-risk substantial changes needing full review
- Route B for lower-risk substantial changes with faster processing, important detail for moderate changes, and minor modifications for low-impact changes.
- Some changes are covered by the Notifiable Trials scheme, needing only notification rather than full approval.
The new clinical trials regulations will allow the MHRA and REC to request further information when considering substantial modification requests.
The MHRA and Research Ethics Committees (RECs) will have more aligned roles and may on occasion request sponsors to modify a trial.
There will be a requirement for UK CTIMPs to recruit the first participant within 2 years of approval, unless an extension is granted, otherwise the approval will lapse.
Under the new regulations, Suspected Unexpected Serious Adverse Reactions (SUSARs) and annual safety reports for all CTIMPs (whether they were submitted via Combined Review or not) will only be reported to the MHRA.
The period a Sponsor has to give written notice to the REC and MHRA for an Urgent Safety Measure (USM) they take will be extended from 3 to 7 calendar days.
Safety of non-authorised non-IMPs should be reported in the same way as IMPs. Accordingly, Serious Adverse Reactions related to non-authorised non-IMPs should be considered as SUSARs and reported to the MHRA.

Transparency, public registration and reporting

All CTIMPs will be legally required to be registered in a public trial registry.
A summary of results must be publicly posted within 12 months of trial completion.
Investigators must offer a lay summary of results to participants or their representatives.
Waivers to transparency obligations may be requested in limited circumstances. A waiver means the sponsor is not required to fulfil outlined transparency obligations for that particular trial.

Data retention and record-keeping

The mandatory minimum retention period for clinical trial master files (TMFs) and associated records will increase from 5 years to 25 years.
If the trial data support a UK marketing authorisation, additional retention requirements will apply.
All records, including electronic records, must remain accessible, legible and retrievable.

ICH E6(R3): Modernising Good Clinical Practice

ICH E6(R3) was finalised (Step 4) on 6 January 2025. The MHRA has confirmed its intention to require implementation of E6(R3) at the same time as the new UK CTIMP regulation timeline (from 28 April 2026).
Key principles of E6(R3) include:
- Risk-based and proportionate oversight and monitoring
- Quality embedding into protocol and process design rather than relying purely on audit checks later
- Enhanced roles and responsibilities for investigators, sponsors, and delegated parties (including training, documentation of oversight, governance)

• References to ICH E6(R3) already appear in MHRA guidance on safety collection and verification, including expectations around qualification and training of investigators.

Why this matters

These reforms are intended to streamline regulatory processes, reduce administrative burden and accelerate access to innovative treatments, while maintaining or enhancing participant safety, ethical oversight, and data integrity.
The new regulations will also align the UK more closely with international standards of clinical trial regulation and modern GCP expectations.
The transparency and reporting obligations will enhance public trust and accountability in clinical research.

Useful resources