UK MHRA Guidance: Clinical Investigations for Medical Devices

As the UK strengthens its regulatory framework for medical devices, the Medicines and Healthcare products Regulatory Agency (MHRA) outlines a clear system for sponsors intending to conduct clinical investigations. These investigations are essential for generating evidence on device performance and safety before market approval. The MHRA guidance, “Clinical investigations for medical devices": that provides a structured route that sponsors must follow before initiating any study in the UK.

Why Clinical Investigations Require MHRA Notification

Clinical investigations help determine whether a device is safe and performs as intended in real-world use. MHRA requires advance notification so the agency can ensure that the proposed study design, device risk profile, and ethical safeguards are properly justified. Notification initiates a formal validation and review process, which must be completed before a study can begin.

Clinical Investigation Enquiries and Use of MHRA Guidance

Sponsors often reach out to the MHRA early to clarify classification, study design, or regulatory expectations. This early interaction reduces delays and helps ensure that applications are aligned with MHRA requirements. The agency also provides a validation checklist that describes exactly what documentation must be included in the submission. MHRA uses this checklist to confirm completeness before moving into scientific assessment.

Notifying MHRA of a Planned Clinical Investigation

The notification is submitted via MHRA’s online platform and must include the full clinical investigation plan, device description, manufacturing information, risk analysis, supporting evidence, insurance documentation, and ethical approvals. After receiving the application, MHRA reviews it first for completeness and then for scientific and safety considerations. A study cannot begin until MHRA confirms that it has no objections.

Fees and the SME Fee Waiver Pilot

Clinical investigation submissions require payment of a review fee, which supports MHRA’s evaluation activities. To encourage innovation among early-stage companies, MHRA offers a pilot fee waiver for micro and small enterprises. Eligible sponsors must demonstrate their SME status and meet specific conditions to qualify.

MHRA’s Assessment of a Clinical Investigation

Once validated, the submission undergoes detailed review. MHRA examines whether the study is scientifically sound, whether the device risks are adequately controlled, and whether the protocol can produce meaningful evidence. The agency may request clarifications or additional information. Only when MHRA raises no remaining concerns may the investigation proceed.

Combined Review for Studies Involving Both Devices and Medicinal Products

For investigations involving both an investigational medicinal product (CTIMP) and a medical device, MHRA offers a combined review with the Health Research Authority (HRA). This integrated pathway allows sponsors to submit a single application, streamline timelines, and receive coordinated scientific and ethical review.

Managing Amendments to an Ongoing Investigation

If a sponsor needs to make a significant change to the device, protocol, risk analysis, or study documentation, the amendment must be submitted to MHRA before implementation. The agency determines whether the amendment is substantial and whether it affects the authorization previously granted. Sponsors must wait for MHRA’s acceptance before applying major changes.

Early Termination or Temporary Halt

If safety concerns, device malfunctions, or operational issues occur, sponsors must promptly notify MHRA of any temporary halt or early termination. The agency requires a clear explanation and plans for participant follow-up, ensuring that any potential risks are fully managed.

Northern Ireland Requirements

Due to the Northern Ireland Protocol, device investigations in Northern Ireland may fall under EU MDR/IVDR rules rather than exclusively UK MDR 2002. Sponsors must follow the appropriate pathway based on where the study is conducted and ensure compliance with all relevant UK and EU requirements.

Healthcare Establishments and Special Circumstances

Hospitals or healthcare institutions conducting their own investigations, particularly with modified or custom-made devices, must still meet MHRA expectations regarding documentation, risk management, and traceability. These responsibilities apply even when the institution acts as both sponsor and investigator.

Ethical Approval from HRA and HCRW

In addition to MHRA authorization, sponsors must obtain ethical approval from the Health Research Authority (HRA) and Health and Care Research Wales (HCRW). Approval from these bodies ensures proper oversight of consent processes, participant protection, data governance, and study conduct. Clinical investigations may only begin when both MHRA and ethics approvals are in place.

MHRA’s guidance establishes a well-structured, transparent pathway for notifying and conducting clinical investigations for medical devices. While the process requires thorough documentation and careful coordination, it ensures that studies begin with clear regulatory oversight, ethical safeguards, and proper scientific justification. Sponsors who understand and prepare for these requirements can significantly reduce delays and improve the overall efficiency of bringing innovative medical devices into clinical evaluation.

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