MHRA Clinical Investigations for Medical Devices, A Practical Guide for UK Manufacturers

MHRA Clinical investigations are a critical component of medical device development and regulatory approval. For many manufacturers, generating robust clinical evidence is necessary to demonstrate safety, performance and clinical benefit before a device can achieve UKCA marking or access other regulated markets. In Great Britain, the Medicines and Healthcare products Regulatory Agency (MHRA) oversees clinical investigations involving medical devices and has established specific requirements that manufacturers must follow before commencing a study. Understanding when notification is required, how the application process works and what obligations continue throughout the investigation is essential for maintaining compliance and avoiding delays. The MHRA’s latest guidance on notifying clinical investigations was updated in January 2026 and provides important clarification for manufacturers navigating the UK regulatory framework.

What Is a Clinical Investigation?

A clinical investigation is a systematic study involving human participants that is conducted to assess the safety, performance or clinical effectiveness of a medical device. Clinical investigations generate evidence that supports regulatory submissions and provides assurance that a device performs as intended under real world conditions.

For many products, particularly higher risk devices and novel technologies, clinical evidence forms a central component of conformity assessment. Clinical investigations may support UKCA marking in Great Britain, CE marking in Europe or broader international regulatory submissions. The exact evidence requirements depend on the classification, intended purpose and risk profile of the device.

When Must the MHRA Be Notified?

Manufacturers planning a clinical investigation in Great Britain must notify the MHRA at least 60 days before the intended start of the investigation (if authorisation is required for the clinical investigation) . This notification initiates the formal assessment process and allows the MHRA to review the proposed study.

The requirement applies when clinical evidence is being generated to support regulatory approval or market access. However, not every study requires a clinical investigation application. Determining whether notification is necessary depends on the nature of the device, the study objectives and the intended use of the resulting data.

The MHRA provides a decision flow chart to help organisations determine whether a clinical investigation application is required. Early assessment of applicability is important because unnecessary submissions create delays, while failure to notify when required can result in regulatory non compliance.

Situations Where Notification May Not Be Required

Not every clinical activity involving a medical device falls within the MHRA notification framework.

For example, notification is generally not required where a device has been manufactured in house and is used exclusively for an organisation’s own patients, with no intention of placing the device on the market. In this scenario, the activity remains within the organisation’s own healthcare environment and does not support commercialisation.

However, circumstances change when evidence is being generated to support a future commercial product. If a device that has previously been manufactured and used in house is supplied to another organisation for the purpose of collecting safety or performance data to support commercialisation, MHRA notification may become necessary.

Understanding this distinction is particularly important for academic institutions, NHS organisations and early stage innovators transitioning from internal development to commercial product development.

MHRA Regulatory Advice Meetings

Before commencing a clinical investigation, many manufacturers benefit from engaging directly with the MHRA through a regulatory advice meeting.

The MHRA Clinical Investigations Team offers dedicated meetings that provide guidance on navigating the regulatory pathway and understanding clinical investigation requirements. These meetings can help clarify expectations around study design, evidence generation and submission planning.

It is important to understand that the MHRA does not review or approve individual documents during these meetings. Instead, the focus is on providing regulatory guidance and helping organisations understand how requirements apply to their specific circumstances.
For innovative technologies or first time manufacturers, these discussions can significantly reduce uncertainty and improve submission quality.

Understanding Clinical Investigation Fees

Clinical investigation applications are subject to MHRA fees, which can represent a significant consideration for startups and smaller organisations.

The fee structure varies depending on the nature of the submission and the organisation involved. While costs may be substantial, the MHRA provides fee easements for qualifying small and medium sized enterprises.

To access SME fee reductions, organisations must provide an MHRA SME approval letter at the point of application submission. Without this documentation, the easement cannot be applied.

The payment structure allows 50 percent of the fee to be paid following validation of the application, with the remaining balance payable within six months of the first invoice. Manufacturers should note that failure to pay the outstanding balance can have serious consequences, including revocation of approval and suspension of the clinical investigation.

Importantly, fee easements do not apply to regulatory advice meetings.

How to Submit a Clinical Investigation Application

Applications for medical device clinical investigations in Great Britain are submitted electronically through the Integrated Research Application System, commonly known as IRAS.
IRAS acts as the central platform for preparing and submitting clinical investigation applications. Manufacturers should ensure that all required documentation is complete before submission, as incomplete applications can delay validation and assessment. The MHRA provides a validation checklist that should be reviewed carefully before submission. This checklist helps applicants confirm that all required documents and supporting information have been included. Preparing a complete and well structured application significantly improves the likelihood of efficient review and reduces the risk of avoidable delays.

What Happens After Submission?

Once the MHRA receives an application, the first stage is validation. During validation, the agency reviews the submission against the published checklist to confirm completeness.

If the application is valid, the MHRA typically confirms within five working days that the formal 60 day assessment period has started. If issues are identified during validation, the applicant will be notified and the assessment clock will not begin until a satisfactory response is received.

Day one of the assessment period is defined as the day immediately following validation. This means that submission date and assessment start date may differ depending on how quickly validation is completed.

The MHRA Assessment Process

During the assessment period, MHRA experts evaluate both the device and the proposed clinical investigation.

The review focuses on safety, device performance and the suitability of the investigation design. Assessors may request additional information if clarification is needed. Prompt responses from applicants are essential because delays in communication can affect review timelines.

Where potential grounds for objection are identified, the MHRA may arrange a teleconference with the applicant. These discussions aim to clarify concerns, explore solutions and resolve issues within the assessment period wherever possible.

By the end of the 60 day review period, the MHRA will issue a formal decision. This will either be a letter of no objection, allowing the investigation to proceed, or an objection outlining reasons why the proposed study cannot continue in its current form.

Managing Amendments During a Clinical Investigation

Approval is not the end of regulatory obligations. Once a letter of no objection has been received, manufacturers must continue to notify the MHRA of proposed changes.
Amendments may involve modifications to the device under investigation, updates to the clinical investigation plan, changes to investigators or participating institutions, or amendments requested by research ethics committees. Importantly, organisations must wait for a further MHRA letter of no objection before implementing these changes. Failure to notify significant amendments can result in enforcement action and potential prosecution. Amendment submissions are also managed through IRAS, ensuring continuity of documentation throughout the investigation lifecycle.

Serious Adverse Events and End of Study Reporting

Manufacturers conducting clinical investigations must maintain robust reporting systems throughout the study. Serious adverse events and other reportable incidents must be managed in accordance with applicable regulatory requirements. These obligations help ensure participant safety and allow emerging risks to be assessed promptly. At the conclusion of the investigation, manufacturers are required to submit end of study reports to the MHRA. These reports provide a summary of study outcomes and contribute to the overall clinical evidence package supporting future regulatory submissions.

Common Mistakes to Avoid

Several recurring issues can delay clinical investigations or create compliance challenges.
One common mistake is underestimating the time required for application preparation and validation. Another is failing to engage with the MHRA early when regulatory uncertainty exists.
Organisations sometimes overlook amendment notification requirements, assuming that approval covers all future changes. In reality, ongoing communication with the MHRA remains essential throughout the investigation. Failure to plan for fees, SME documentation or reporting obligations can also create avoidable administrative challenges. Early preparation significantly reduces these risks.

LFH supports medical device manufacturers throughout the clinical investigation process, from regulatory strategy and protocol development to MHRA submissions and ongoing compliance management. Our team helps organisations navigate UK clinical investigation requirements efficiently, generate robust clinical evidence and maintain progress toward UKCA marking and broader market access.

FAQs – MHRA Clinical Investigations