UK MHRA Med Dev Guidance: Submitting a Clinical Investigation Proposal for MHRA Assessment

Clinical investigations of medical devices require a comprehensive submission that provides the MHRA with sufficient information to assess the safety and performance of the device. The MHRA guidance Clinical Investigations: Compiling a Submission explains how manufacturers should notify the MHRA of a planned clinical investigation and sets out the information and supporting documentation required for assessment.

Why This Guidance Is Important

The guidance provides manufacturers with a structured approach to preparing a clinical investigation submission. It covers the documentation required for all applications as well as additional information that may be required in specific circumstances.

The requirements differ depending on whether the clinical investigation is conducted in Great Britain, Northern Ireland, or both. Clinical investigations in Great Britain must meet the requirements of the UK Medical Devices Regulations 2002, while investigations in Northern Ireland must meet the applicable EU MDR requirements. Where sites are located in both Great Britain and Northern Ireland, a single application under the EU MDR can cover the same clinical investigation.

Before Submitting the Clinical Investigation

Before notifying the MHRA, manufacturers should ensure that the device has been manufactured and tested for safety and performance. The submission should contain the information necessary to demonstrate compliance with the applicable essential requirements or General Safety and Performance Requirements, except for requirements that are specifically the subject of the investigation.

Applications must be submitted through the Integrated Research Application System (IRAS). The application form and relevant supporting documents should be completed and uploaded through IRAS. All information must be provided in English, and supporting documents should be complete, readable, and preferably supplied as searchable PDFs.

Required Submission Documentation

The IRAS checklist identifies the documents that should be included in the submission. These include the covering letter, clinical investigation plan, investigator's brochure, participant information sheet and consent form, investigator CVs, device details, requirements checklist, risk analysis, instructions for use, device labels, testing information, clinical experience, applicable standards, and other supporting documentation where relevant.

Additional documents may be required depending on the characteristics of the device and the circumstances of the investigation. These can include sterilisation validation reports, software information, biological safety assessments, information on animal tissues, and information on medicines, human blood derivatives, or non-viable human tissues and cells incorporated into the device.

Clinical Investigation Plan and Study Design

The clinical investigation plan should align with ISO 14155:2026 and clearly describe the purpose, design, and conduct of the investigation.

The submission should include the aims and objectives, study design, randomisation, study classification where applicable, blinding approach, sample size justification, number of centres, study duration, patient selection criteria, and withdrawal criteria.

The plan should also describe primary and secondary endpoints, data collection and follow-up, analysis populations, statistical methods, significance levels, handling of missing data, and procedures for reporting serious adverse events and adverse device-related incidents. Planned interim analyses and the approach for controlling type I error should also be described where applicable.

Device, Risk and Supporting Evidence

The submission should provide sufficient information for the MHRA to understand the device, including its intended purpose, mode of action, design, components, operation, and associated risks.

Risk analysis should preferably follow EN ISO 14971:2019, with risks eliminated or reduced as far as possible through device design and manufacture. The submission should also include information on applicable standards, instructions for use, device labels, bench and pre-clinical testing, clinical experience, and relevant safety and performance evidence.

For investigational devices that include software, the submission should address software development, risk management, configuration management, system requirements, verification, problem resolution, and release processes. Software development should, wherever possible, follow the principles of IEC 62304.

Specific Supporting Information

Certain devices require additional documentation as part of the MHRA assessment.

For sterile devices, manufacturers should provide information demonstrating that the sterilisation process can be delivered effectively and reproducibly. For patient-contacting devices, a biological safety assessment should address biocompatibility, biological hazards, materials, and relevant risks.

Where applicable, the submission should also include information concerning animal tissues, medicinal substances, human blood derivatives, non-viable human tissues and cells, and other incorporated materials.

As clinical investigation submissions are assessed against the applicable regulatory requirements, manufacturers should ensure that the submission is complete, clearly presented, and supported by the necessary safety, performance, risk, clinical, and technical documentation. A structured approach to compiling the submission can help ensure that the MHRA receives the information required to assess the proposed clinical investigation.

References

• MHRA: Clinical Investigations: Compiling a Submission (updated 6 August 2026).

• MHRA: Submitting a Clinical Investigation Proposal for MHRA Assessment (updated 6 August 2026).