Uk MHRA Med Dev Guidance: Clinical Investigations for Medical Devices

As medical device development becomes increasingly focused on clinical evidence, sponsors and manufacturers must understand when a clinical investigation requires regulatory notification and how to manage the study throughout its lifecycle. In the UK, clinical investigations may be required to generate evidence supporting UKCA, CE or CE UKNI marking, making regulatory planning an important part of device development.

The Medicines and Healthcare products Regulatory Agency (MHRA) has updated its guidance, Clinical investigations for medical devices, to explain how sponsors should notify the Agency of their intention to conduct a clinical investigation.

The guidance covers application requirements, assessment timelines, amendments, safety reporting, fees, Northern Ireland requirements, and post-study obligations, with the latest update published on 12 August 2026.

When Is an MHRA Clinical Investigation Application Required?

Manufacturers may need to conduct a clinical investigation to generate evidence for regulatory marking of a medical device. For applicable studies in Great Britain, sponsors must notify the MHRA at least 60 days before starting the clinical investigation.

The guidance recommends using the relevant MHRA flow chart and accompanying guidance to determine whether an application is required. The regulatory pathway differs depending on whether the investigation is conducted in Great Britain, Northern Ireland, or across both territories.

A notification is generally not required where a medical device already has UKCA, CE or CE UKNI marking for the specific purpose being investigated.

Healthcare establishments may also benefit from specific exemptions. For example, notification is not required for certain devices manufactured in-house for a healthcare establishment's own patients where there is no intention to place the device on the market.

Preparing and Submitting the Application

Clinical investigation applications are submitted electronically through the Integrated Research Application System (IRAS).

Sponsors should ensure that the application is complete and aligned with the applicable MHRA submission requirements before submission. The Agency provides a validation checklist to help manufacturers identify missing or incomplete information before the application enters the assessment process.

The submission should support the MHRA's evaluation of both the safety and performance of the medical device and the scientific and methodological design of the proposed clinical investigation.

Early regulatory planning is therefore important, particularly for manufacturers developing innovative devices or studies involving complex clinical designs.

MHRA Assessment and the 60-Day Timeline

For clinical investigations conducted in Great Britain, MHRA begins the formal assessment period after the application has been validated.

The Agency aims to contact the applicant within five working days following receipt and validation of the application to confirm that the 60-day assessment period has started or identify issues that need to be addressed. The assessment evaluates the safety and performance of the device as well as the proposed design of the clinical investigation.

Where potential grounds for objection are identified, MHRA may engage with the sponsor to clarify issues and seek resolution during the assessment period.

By the end of the assessment period, MHRA will issue a decision stating whether it has an objection or no objection to the proposed clinical investigation.

This makes submission quality and timely responses particularly important for sponsors working against clinical development timelines.

Fees and SME Support

Clinical investigation applications are subject to MHRA fees, with payment requirements linked to the submission and regulatory decision process.

The guidance also provides fee easements for eligible small and medium-sized enterprises. Under the SME easement, 50% of the applicable fee is requested following validation, with the remaining 50% payable within six months of the first invoice.

In addition, MHRA has extended its clinical investigation fee waiver programme for micro and small UK enterprises into 2026–2027. The programme provides a limited number of full fee waivers for eligible innovative medical device investigations.

The 2026–2027 programme includes eligible Class I, IIa, IIb and Class III devices, excluding active implantable devices. Applicants must demonstrate that the device is innovative, addresses an unmet clinical need and has potential to benefit patients, care providers or the wider health and social care system.

Managing Amendments After Approval

Regulatory responsibilities continue after MHRA provides a no-objection decision.

For investigations in Great Britain, sponsors must notify MHRA of proposed amendments and wait for the appropriate no-objection response before implementing changes. Amendments can include changes to the investigational device, clinical investigation plan, study documentation, investigators or investigating institutions, as well as changes requested by an ethics committee.

Sponsors must provide a covering letter, a summary and justification of the proposed changes, red-lined and clean versions of amended documentation, and a signed statement confirming that the changes do not predictably increase risk to patients, users or third parties.

Effective amendment management is therefore an important component of clinical investigation compliance and study lifecycle management.

Safety Reporting and Ongoing Regulatory Obligations

Sponsors have continuing reporting responsibilities throughout the investigation.

For applicable Great Britain studies, serious adverse events and other reportable events must be recorded and notified to MHRA. The guidance also requires quarterly summary reports providing an update on the overall safety profile of the investigation.

Sponsors must additionally report study deviations relating to UK study sites and maintain appropriate documentation of corrective and preventive actions where applicable.

Early termination or temporary halts must also be notified to MHRA, with appropriate justification and final study documentation submitted according to the applicable requirements.

These obligations demonstrate that regulatory compliance does not end once a clinical investigation receives approval. Sponsors must maintain continuous oversight of safety, study conduct, amendments and reporting throughout the investigation lifecycle.

Great Britain vs Northern Ireland

One of the most important considerations for sponsors is the different regulatory framework applicable to Great Britain and Northern Ireland.

Northern Ireland continues to operate under EU medical device legislation, meaning the EU Medical Device Regulation (MDR) and In Vitro Diagnostic Medical Device Regulation (IVDR) apply to relevant activities.

Clinical investigations involving Northern Ireland sites must therefore be assessed against the applicable EU MDR requirements and MHRA processes. A single application can cover the same investigation where sites are located in both Northern Ireland and Great Britain.

The assessment and modification requirements also differ. For Northern Ireland, MHRA distinguishes between substantial and non-substantial modifications, with substantial modifications requiring authorisation before implementation.

What This Means for Regulatory and Clinical Teams

For Regulatory Affairs and Clinical Research professionals, the updated MHRA guidance highlights the importance of integrating regulatory strategy into clinical investigation planning from the beginning.

Teams should determine the applicable regulatory pathway early, confirm whether an MHRA application is required, prepare a complete submission, understand assessment timelines, and establish processes for amendments, safety reporting, deviations, and study closure.

For global device programmes, the Great Britain and Northern Ireland requirements should also be evaluated separately because different regulatory frameworks and procedural expectations may apply.

A well-planned clinical investigation strategy can help manufacturers avoid submission delays, maintain regulatory compliance and generate clinical evidence that supports the broader medical device development and market access strategy.

References

• MHRA Guidance: Clinical investigations for medical devices — updated 12 August 2026.