England National Companion Guide

A clinical evaluation, which involves looking at published clinical data to prove that the medical device works as intended and is safe to use, is not the same as a clinical investigation (CI). A CI may form part of a clinical evaluation. For example, if not enough pre-existing evidence exists to demonstrate that the device conforms to the essential requirements, a specifically designed CI may be necessary. In this case, manufacturers will need to notify MHRA in advance of the investigation. MEDDEV 2.7/4 includes guidance on deciding whether a CI is necessary. If a manufacturer intends to conduct a CI in the UK, they must inform MHRA at least 60 days before starting the investigation. This flowchart is useful for determining whether it is necessary to submit a study to MHRA in advance.

If using clinical data from other jurisdictions, it will be necessary to compare use cases, target populations, healthcare settings, and clinical care standards across both geographies. It is important to identify which evidence elements are, or are not, transferable across jurisdictions.

Additional insights related to clinical investigations of medical devices in England include:

• For clinical investigations that are also submitted to the FDA or other regulatory authorities, manufacturers should clearly indicate whether the UK and non-UK protocols are the same. If the protocols are not the same, the areas of difference should be referenced, and an explanation of the reasons for the differences should be provided. The objectives of a clinical investigation which is being conducted in the UK and also in a country or countries outside the UK may be wider than those required by the UK MDR 2002/EU MDR. Changes to protocol requested by other regulatory authorities should be copied to the MHRA. At such times, manufacturers should indicate whether the changes instigated by the non-UK regulatory authority will also be made to the UK protocol.
• The decision about selecting the most appropriate control group depends on the aims of the investigation. For some devices, it would only be possible to demonstrate claims adequately by comparison with a separate or untreated group. If control groups are necessary, they should be randomized and prospective, except in exceptional and justifiable circumstances. Pivotal/confirmatory studies should have a control where clinically relevant and appropriate to do so. For all studies, lack of a control group must be justified.
• Care should be taken in choosing endpoints to support the stated aims and objectives of the clinical investigation under normal conditions of use. Methods of supporting the demonstration of these endpoints should, as far as possible, be objective rather than subjective.

Developers should also be aware of compliance requirements related to product data and security, such as the Data Security and Protection Toolkit (DSPT), NHS Information Governance (GDPR and UK Protection Law compliance), and Clinical Risk Management DCB0160.

The AI and Digital Regulations Service is a good resource for requirements for medical devices and digital technologies in England (i.e., requirements for a quality management system (QMS), product technical documentation, data security, clinical safety). MHRA also maintains a library of guidance documents.

All medical devices must be registered with the MHRA before they can be placed on the market in Great Britain (England, Wales, and Scotland). If the manufacturer is based outside of the UK, they must appoint a single UK Responsible Person to take responsibility for all of their medical devices. The UK Responsible Person will then assume the responsibilities of the manufacturer in terms of registering the device with the MHRA.

For Class I medical devices, there is no specific review timeline, but instead a self-certification process. MHRA tends to register products following this route within a week of submission.

For Class IIa, IIb, and III medical devices, approval from a UK Approved Body (UKAB) can take one to two years. This timeline is impacted in part by the current backlog of device reviews of the closely related EU Notified Bodies; however, this backlog is expected to improve with the introduction of new conformity assessment routes by MHRA. Additionally, in May 2024, MHRA released a statement of policy intent for recognition by the UK of approvals of medical devices from international regulators.

The MHRA can be contacted via email with questions relating to product submissions. This consulting service may charge a fee in the future.

For companies seeking advice/support from NICE on the development of a health technology, NICE Advice operates separately from guidance production, offering fee-based advice and support around evidence generation or other challenges relating to market access. For general questions, there is an online contact form. Additionally, NICE provides a number of guidance documents on a variety of topics on their website.

MHRA does not have a broad pre-submission process for medical devices. This type of process is being developed in tandem with other relevant agencies through the Innovative Devices Access Pathway (IDAP) programme, but it is currently a limited access pilot program for a single cohort of devices.

Regulatory advice meetings: MHRA’s clinical investigations team can advise developers on planning clinical investigations.

Coordinated assessment pathway process: MHRA is collaborating with the Health Research Authority (HRA) on the coordinated assessment pathway, which involves the two organizations sharing information during the assessment of medical device clinical investigations. For this process, they require the MHRA clinical investigation application to be submitted first, and then the research ethics committee (REC) application to be submitted as soon as MHRA has confirmed the device’s application to be valid.

NICE Advice Service: Provides comprehensive pre-submission guidance. Resources include scientific advice meetings, the health economic model peer review service (META tool), “NICE surgery” meetings (1 hour meeting that is suitable for any point in the process), therapeutic landscape reviews (most suitable for early in the submission process), and system engagement meetings (most suitable for companies with Stage 3 clinical trial data who are preparing to formally submit).

UK Conformity Assessed (UKCA) marks are administered through the MHRA. Companies wanting to market a medical device in England must register the device with the MHRA through the Device Online Registration System (DORS).

The Digital Technology Assessment Criteria (DTAC) for health and social care was developed in response to developers and entities making buying and commissioning decisions that are looking for clear direction on how to build and buy good digital health technologies. It provides a way to review a product’s clinical safety, data protection, technical security, interoperability, and usability and accessibility standards. It also aligns with NICE’s Evidence Standards Framework for digital health technologies.

DTAC provides the national baseline criteria for DHTs entering and already used in the NHS and social care. For developers, it sets out what is expected for entry into the NHS and social care. Achieving the criteria laid out in the DTAC provides developers with a consistent way to present information to organizations buying and using digital health technologies. It does not imply that products will automatically be granted reimbursement or patient access if successfully completed.