UK MHRA Med Dev Guidance: Clinical Investigations for Medical Devices - What Sponsors Need to Know in 2025

Sharan Murugan
Aug 6
3 min read

Medical devices, whether diagnostic, therapeutic, or assistive, undergo rigorous scrutiny before entering the UK market. One of the most critical components in this process is the clinical investigation—designed to assess a device’s safety and performance in real-world conditions.

The Medicines and Healthcare products Regulatory Agency (MHRA) plays a central role in overseeing these investigations within Great Britain and Northern Ireland. Their comprehensive guidance, titled “Clinical Investigations for Medical Devices”, outlines regulatory pathways, requirements, and obligations for manufacturers and sponsors intending to conduct clinical trials with investigational medical devices.

Clinical Investigation Enquiries

Before initiating a clinical investigation, sponsors are encouraged to contact the MHRA for early guidance. Especially in complex or novel cases, this proactive engagement helps streamline the validation and assessment process.

MHRA's Clinical Investigation Unit is available to address questions about regulatory expectations, timelines, and documentation—ensuring clarity from the outset.

MHRA Guidance and Responsibilities

Manufacturers intending to conduct clinical investigations must comply with the UK Medical Devices Regulations 2002 (as amended). Clinical investigations are required if:

The device is non-CE/UKCA marked
The device is CE/UKCA marked but used outside its intended purpose
There are modifications impacting safety/performance

The sponsor must demonstrate that:

The clinical investigation is scientifically and ethically justified
Risk is appropriately managed
The investigation is designed to generate robust safety and performance data

Validation Checklist

MHRA provides a validation checklist to ensure that clinical investigation submissions are complete. Applications that fail this validation stage will be rejected, resulting in delays.

The checklist includes:

Signed cover letter
Declaration of conformity
Clinical investigation plan (CIP)
Investigator’s brochure
Ethics opinion
Labeling and instructions
Data protection compliance

Only after successful validation does the 60-day assessment period begin.

How to Notify the MHRA

Notifications must be submitted via the MHRA’s online Device Registration and Clinical Investigation (DaRCI) portal. Once submitted, MHRA will:

Acknowledge receipt
Conduct validation (within 5 days)
Begin the 60-day assessment period

Sponsors should not begin investigations until either the MHRA grants a notice of no objection, or the 60-day statutory period ends without a response.

Fees

MHRA charges a £5,103 fee for each clinical investigation notification, regardless of device class. Fees are payable through the MHRA portal during application submission.

Assessment

Once validated, MHRA conducts a scientific and regulatory review of the submitted investigation. The review focuses on:

Clinical justification
Risk/benefit assessment
Ethics review
Investigator suitability
Data management and monitoring plan

If deficiencies are identified, the MHRA may request clarifications or issue an objection.

Combined Review of CTIMPs and Medical Devices

For combined trials involving both a medical device and a medicine (such as drug-delivery systems or combination products), the sponsor may require a combined review involving:

The MHRA (for both CTIMP and device aspects)
The Health Research Authority (HRA)

MHRA provides a dedicated process for such integrated submissions to avoid duplicated efforts and ensure consistency.

Amendments

Any substantial amendments to the clinical investigation (e.g., protocol change, new device version, change in investigator or site) must be notified to the MHRA. Submissions must include:

Amendment form
Summary of changes
Justification
Updated documents

Sponsors must wait for MHRA’s approval before implementing changes.

The guidance also covers performance studies for in vitro diagnostics. Key requirements include:

Demonstration of analytical performance
Justification of clinical performance study design
Compliance with ethical and data protection standards

Sponsors can access further documentation, templates, and contact information via the official MHRA guidance page: clinical investigation for a medical device