Guidance

Guidance for clincal investigators

Published 30 March 2026

This guidance helps clinical investigators understand what needs to be included in a submission notifying the MHRA of a manufacturer’s plans to undertake a clinical investigation.

In order to demonstrate compliance with the essential requirements of the UK Medical Devices Regulations 2002 (SI 2002 No 618, as amended)(UK MDR 2002) and the general safety and performance requirements of the (EU) Medical Devices Regulation 2017/745 (EU MDR) governing safety and performance, and in order to justify the application of UKCA or CE-marking, it will sometimes be necessary for the manufacturer of the device to provide clinical data with which to back up claims made for that device.

This may involve undertaking a specifically designed clinical investigation to:

• verify that, under normal conditions, of use the performance characteristics of the device are those intended by the manufacturer

and

• determine any undesirable side-effects and to assess whether these are acceptable risks when weighed against the intended performance of the device

If such an investigation is necessary, the manufacturer must make an application to the MHRA before the investigation is due to begin. The clinical investigation may only proceed provided no grounds for objection are raised by the MHRA within the statutory review time constraint.

Find out more about how to notify us of a clinical investigation.

We will reach a decision with the help of expert assessors. It is the responsibility of the manufacturer or the sponsor of the study to both notify the MHRA and to submit the documentation required by the UK MDR 2002 or EU MDR to the MHRA. The clinical investigator will normally have no direct contact with the MHRA.

It is a criminal offence for a person to supply a device which does not carry the UKCA, CE or CE marking, apart from in the defined exceptions of devices intended for clinical investigation, custom-made devices, or those with an exemption.

You can find out more about how the MHRA regulates medical devices.

Research ethics committee approval

A relevant ethics committee opinion is required for all clinical investigations of devices falling within the scope of the UK MDR 2002, Part II for medical devices, or Chapter VI of EU MDR. This opinion should be sought either before or in parallel with the notification to the MHRA, normally by the investigator. The manufacturer will be required to submit a copy of the research ethics committee approval to the MHRA.

The MHRA does not accept approvals from independent ethics committees. The manufacturer should seek the opinion of an ethics committee appointed by the Research Ethics Service (RES) unless they can demonstrate why RES appointed committees would not assess their clinical investigation. In such cases, the manufacturer will need to demonstrate that the independent ethics committee appointed was constituted in line with RES guidelines. However, RES will review all clinical investigations due to be conducted outside the NHS and therefore situations where an independent ethics committee is required are not foreseen or expected to arise.

Clinical investigators, however, should be aware that under the provisions of the UK MDR 2002 and EU MDR, a clinical investigation may not proceed if grounds for objection have been raised by the MHRA, even if approval has been granted by a research ethics committee. All RES appointed ethics committees are aware of this requirement.

Grounds for objection

If, after consideration of all the evidence provided, the MHRA considers that the proposed clinical investigation may present unjustifiable risks to public health or safety, we will notify the manufacturer of our objection and the reasons for this decision. Circumstances in which we consider that such risks may exist include:

• a situation where a professional opinion exists stating that the risk benefit analysis is inaccurate

and

• were the investigation to take place, there would be a significant probability of serious illness, injury or death to the patient or user

or

• there are reasonable grounds to suspect that the performance of the device is not that claimed by the manufacturer

or

• insufficient information has been submitted to allow a proper assessment of the safety aspects of the proposed clinical investigation

If the MHRA raises objections to the investigation, the manufacturer should inform the clinical investigator. We will not contact the clinical investigator directly, although we may contact the ethics committee.

The manufacturer may re-submit an application for a proposed clinical investigation, provided the reasons for refusal of the original submission are addressed.

Conduct of a clinical investigation

The MHRA expects that the principles of ICH Good Clinical Practice are followed.

Sponsors and investigators must ensure that the investigation is conducted in full accordance with the approved clinical investigation plan (CIP) and the requirements of the UK MDR 2002 or EU MDR. Deviations from the approved CIP must be reported to MHRA.

There must be adequate monitoring in place to ensure that the rights, safety and well-being of participants are protected.

All information relating to the clinical investigation must be recorded, processed and stored by the sponsor or investigator in such a way that it can be interpreted and reported, and not impact upon the confidentiality of the records and personal data of the participants. The personal data of the participants must be protected in line with General Data Protection Regulations.

There must be an emergency procedure to enable immediate identification of the devices within the investigation. This may be required in the event of an immediate recall of the devices.

Labelling of medical devices

All devices intended for clinical investigation must bear the wording ‘exclusively for clinical investigation’. To avoid misunderstandings about the nature of the clinical investigation, it must be clear that it is the device under investigation and not the patient. All clinical investigators should ensure that the meaning of this wording is clearly understood by all staff using or coming into contact with the device. The device must be segregated, where possible, from devices in routine use. In some cases, the clinical investigator may consider it necessary to attach appropriate warning signs to the device under investigation.

Devices intended for clinical investigation should not bear UKCA, CE or CE marking.

Amendments or modifications

All proposed changes to the clinical investigation whether relating to the device, aspects of the clinical investigation plan, investigators or investigating institutions must be notified to the MHRA.

Adverse incidents

Any adverse incident involving a medical device undergoing clinical investigation should be fully recorded and reported to the MHRA.

Humanitarian use of devices without a conformity marking

The use of an individual non-UKCA or non-CE marked device may be authorised by the MHRA on humanitarian grounds, provided that we are satisfied that this would be in the interests of the patient and protection of health. In such cases, the device may not be used until an application is made by the manufacturer to the MHRA for such use and we give due authorisation. MHRA authorisation applies only to the use of the individual device for a named individual within the UK. Failure to comply with these requirements is a criminal offence.

To apply for humanitarian use of a non-UKCA, non-CE or non-CE UKNI marked device the manufacturer and clinician must apply to the MHRA for approval.

Further information

You can find more useful guidance in Designated standard ISO14155 Clinical investigation of medical devices for human subjects: Good clinical practice. It sets out the recommended procedure for a clinical investigation of a medical device. Copies of the standard are available from the British Standards Institution.

If you would like more information about the clinical investigation system and the system for reporting serious adverse events of devices undergoing clinical investigation, you can email info@mhra.gov.uk.

Documentation required for all clinical investigation submissions

If you are notifying the MHRA of a clinical investigation your initial submission should include:

• a covering letter on headed paper
• clinical investigation plan
• investigator’s brochure
• participant information sheet
• participant consent form
• CVs for UK clinical investigators
• device details
• essential requirements checklist or general safety and performance requirements checklist
• risk analysis
• instructions for use of a medical device
• device labels
• summary of all bench testing and pre-clinical testing conducted
• summary of all clinical experience with the device to date
• end of study reports for any concluded clinical investigations that involved the same medical device under investigation
• list of standards met
• sterilisation validation report (where relevant)
• software information (where relevant)
• biological safety assessments of patient contacting materials (where relevant)
• information on animal tissues (where relevant)
• information on any medicine or human blood derivative, or non-viable human tissues and cells incorporated into the device
• research ethics committee opinion (if available)

You can find out more information about compiling a submission and the information you need to include.

Glossary of terms

Active implantable medical device: any active medical device which is intended to be totally or partially introduced, surgically or medically, into the human body or by medical intervention into a natural orifice, and which is intended to remain after the procedure.

Active medical device: any medical device relying for its functioning on a source of electrical energy or any source of power other than that directly generated by the human body or gravity.

Adverse device event: a device-related adverse event.

Adverse event: any undesirable clinical occurrence in a participant whether it is considered to be device-related or not.

Clinical investigation: any systematic investigation or study in human participants, undertaken to verify the safety and performance of a device, under normal conditions of use.

Clinical investigation plan: a document which includes detailed information on the rationale, aims and objectives, design and proposed analyses, methodology, and conduct of the clinical investigation.

Clinical investigator: the person responsible for the conduct of a clinical investigation and who takes the responsibility for the health and safety of the participants involved.

Device intended for clinical investigation: within the context of this document, this is any device intended for use by an appropriately qualified practitioner when conducting clinical investigations in an adequate clinical environment.

Implantable device: any device which is intended to be totally introduced into the human body, or to replace an epithelial surface or the surface of the eye, by surgical intervention and which is intended to remain in place after the procedure. Any device intended to be partially introduced into the human body through surgical intervention and intended to remain in place after the procedure for at least thirty days is also considered an implantable device.

Invasive device: a device which, in whole or in part, penetrates inside the body, either through a body orifice or through the surface of the body. A body orifice includes any natural opening in the body, as well as the external surface of the eyeball, or any permanent artificial opening such as a stoma.

Local research ethics committee: an independent and properly constituted body of medical professionals and non-medical members whose responsibility is to ensure that the health, safety and human rights of the patients participating in a particular clinical investigation are protected.

Medical device: an instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, together with any accessories, including the software intended by its manufacturer to be used specifically for diagnostic or therapeutic purposes or both and necessary for its proper application which:

(a) is intended by the manufacturer to be used in human beings for the purpose of:

• the diagnosis, prevention, monitoring, treatment or alleviation of disease or injury (i)
• diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap (ii)
• the investigation, replacement or modification of the anatomy or of a physiological process (iii)
• the control of conception (iv)

(b) does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, even if it is assisted in its function by such means

and

(c) includes devices intended to administer a medicinal product or which incorporate as an integral part a substance which, if used separately, would be a medicinal product and which is liable to act upon the body with action ancillary to that of the device

Multicentre investigation: a clinical investigation, conducted according to a single clinical investigation plan, which takes place at different investigation sites.

Performance of device: the action of a device with reference to its intended use when correctly applied to the appropriate participants.

Principal clinical investigator: the clinical investigator appointed by the manufacturer to co-ordinate the work in a multicentre clinical investigation or the work of several clinical investigators at one site.

Relevant essential requirements: the essential requirements, or such aspects of the essential requirements as apply to a device, not including, in the case of a device intended for clinical investigation, such of those requirements, or aspects of them, as are the subject of the investigation.

Participant: a human being, who is either a patient or a non-patient volunteer, participating in a clinical investigation.

Surgically invasive: an invasive device which penetrates inside the body, other than through an established body orifice, with the aid or in the context of a surgical operation.