You may need to carry out a clinical investigation as part of the process to obtain a UKCA, CE or CE UKNI marking for your medical device. You must inform the MHRA if you are planning to do this at least 60 days before starting your investigation.

Does my study require a clinical investigation application?

For studies in Great Britain, please use this flow chart and accompanying guidance to determine if you need to submit an application to MHRA. In August 2025, MHRA published updated versions of these documents. Please review the latest available guidance and ensure you are aware of its contents with respect to clinical investigation applications from this date.

For studies in Northern Ireland or Great Britain and Northern Ireland, use the flow chart and accompanying guidance in the Northern Ireland section below.

Note: a notification to the MHRA will not be required for medical devices that are UKCA, CE or CE UKNI marked for the purpose that is under investigation.

Applications under Annex XVI of the Medical Device Regulation (EU) 2017/745 (MDR) for devices with no intended medical purpose cannot be accepted in GB.

Special circumstances for healthcare establishments

You do not need to notify us of a clinical investigation if:

you have manufactured the medical device in-house for your own patients with no objective to place it on the market

You may need to notify the MHRA of a clinical investigation if:

you want to provide a medical device to another organisation, that up until now has been manufactured in-house for patients, for data to support safety and performance of a commercial product

Read more about the Health Institution Exemption for general medical devices to find out whether an exemption applies to your study.

Please refer to the flow chart and accompanying guidance to help determine if you need to submit an application to MHRA.

Contact us

Clinical investigation enquiries

For specific enquires relating to applications for clinical investigations, contact info@mhra.gov.uk and ensure you add ‘clinical investigation enquiry’ in the subject line.

Regulatory advice meetings

The MHRA clinical investigations team can offer a comprehensive device regulatory advice meeting.

We cannot review individual documents but we can provide guidance on navigating the regulatory landscape.

See our information on fees regarding the charges for a regulatory advice meeting

To request a regulatory advice meeting, contact the Head of Clinical Investigations mark.grumbridge@mhra.gov.uk.

Fees

See section of our fees page.

A fee under the Medical Devices Regulations 2002:

(a) shall be payable when the notice to which it relates is given to the Secretary of State;

and

(b) shall accompany that notice when it is given.

The fees detailed on our fees page also cover applications for device studies in Northern Ireland

Payment for a clinical investigation

Details of how to make a payment to MHRA can be found here.

We will create an invoice for the payment and to assist us with the invoice please ensure you provide us with a purchase order number as soon as possible and confirm who is responsible for the payment.

Once you have received your invoice and made the payment, you should send evidence of payment by email to CI-applications@mhra.gov.uk and your assigned Regulatory Handler, quoting the MHRA reference (CI/XXXX/XXX).

We will not provide a final regulatory decision (approval or objection letter) on the application until we have received payment.

Payment easements for small, and medium enterprises

Easements are available to SME for clinical investigations. At the point of submission of the application you must provide the MHRA SME approval letter for the easement to be considered.
Upon receipt of a validation of an application MHRA will request 50% of the fee and the remaining 50% will be payable within six months after the first invoice has been issued.
If the final 50% of the outstanding fee is not paid, then any approval letter for a clinical investigation provided by MHRA will be revoked resulting in the clinical investigation being stopped.
In the case of an objection or a withdrawal of an application the remaining fee is due
No easement is offered for device regulatory advice meetings
For further information, see Payment easements and waivers for small and medium companies

Pilot of a medical device clinical investigation fee waiver programme for micro and small sized enterprises

Fee waiver programme for micro and small sized enterprises intending to conduct clinical investigations with innovative medical devices

The MHRA is extending its fee waiver programme into 2026-2027, beginning 20 April 2026.

A total of ten clinical investigation application fee waivers will be available for eligible small and micro sized UK enterprises.

The programme aims to support patient access to innovative devices by testing the impact of removing regulatory costs for smaller sized enterprises, where fees might act as a barrier to growth or innovation.

Fee waiver programme details

Duration: The programme will run from 20 April 2026 until 5 April 2027 or until such time as all fee waivers have been granted.

Waivers available: A total of ten fee waivers will be available for Class I, IIa, IIb and, now also include Class III, but not active implantable devices.

Effect: The usual clinical investigation application fee will be completely waived for successful applicants.

Note:

Only one waiver per applicant can be approved
We will accept applications for studies where it involves a CTIMP however, the fee waiver is only for the device aspect of the application and the full fee is still payable for the CTIMP review

Waiver eligibility conditions

To be eligible, the following conditions must be met:

The applicant can show the device meets the following criteria for an “innovative device”:
- the product is either new or a novel modification of existing technologies;
- there are no solutions that fulfil the same clinical need that have regulatory approval in the UK; and
- the device can be scaled with the end goal of benefiting the health and social care system, patients and/or care providers.
The applicant can show they are based in the UK, and they have obtained micro or small enterprise status from the MHRA prior to submitting their waver application.

See definitions for small and micro sized enterprises.

Check whether you meet innovative device criteria

Prior to submitting a formal submission via IRAS, applicants should seek MHRA confirmation that their device would meet the innovative device criteria for the waiver.
In order to do so, please send a cover letter to CI-applications@mhra.gov.uk containing:

a comprehensive description of the device, and
how it meets the three innovative device criteria mentioned above, and
a brief summary of the planned clinical investigation

The Clinical Investigations team will review the information provided within 5 working days of receipt and will confirm the following:

whether the study meets innovative device criteria, and
whether there are fee waivers available to be granted.

Application process

Applicants planning to submit a clinical investigation application to MHRA should first check whether their device meets the innovative device criteria for the programme with the MHRA. Guidance on how to do to this is given in the section above.
If MHRA has confirmed that the innovative device criteria are met, the applicant should obtain small or micro enterprise status from the MHRA by following the process here.
Once the MHRA have confirmed eligibility and small or micro enterprise status has been obtained, the applicant should proceed to submit their application on IRAS.
This should be done as soon as possible after contacting MHRA to ensure the ongoing availability of waivers.
The MHRA will validate the application in the accordance with standard processes and, if valid, the applicant will be notified that a fee waiver has been granted.
If the application is deemed invalid, the applicant will be notified of the reasons for this decision and have an opportunity to resubmit the application.
When the applicant intends to resubmit the application for validation, they may re-confirm that waivers are available by contacting CI-applications@mhra.gov.uk.

Further information

For guidance on applying for SME status, see Payment easements and waivers for small and medium companies.

Email CI-applications@mhra.gov.uk if you have further questions regarding the fee waiver pilot.

For updates on an ongoing SME status application, please contact sales-invoices@mhra.gov.uk.

Getting started on your application

How to notify the MHRA of your clinical investigation

Start your application via IRAS. Applications are submitted electronically using the Integrated Research Application System (IRAS).

MHRA guidance

Read the guidance on compiling a submission and guidance for manufacturers in Great Britain or guidance for manufacturers in Northern Ireland when preparing your notification application.

Find out how the MHRA approves clinical investigations we are notified about.

Read our information for clinical investigators to find out what is required by clinicians involved in the investigation.

Check the electrical guidance for clinical investigations.

Check our guidance on biological safety assessment of medical devices under clinical investigation.

Check statistical considerations for clinical investigations for presenting statistical information for your clinical investigation.

Read the guidance on applying human factors and usability engineering to medical devices including drug-device combination products.

See the guidance on UKCA markings.

Validation checklist

When we receive your application for a clinical investigation of a medical device our regulatory handers will validate your application against the Clinical investigation application checklist. Use this checklist to help you submit a valid application.

Assessment

This section concerns clinical investigations being conducted in Great Britain only. See the separate section below for studies involving Northern Ireland.

When we have received your documents and validated them, we will contact to you within 5 working days to confirm that the 60-day assessment period has started, or we will let you know if there are any issues. If we raise any issues, the 60-day assessment period will start when we receive a valid response.

Day 1 of the 60 days is taken as being the first day that follows the date of acceptance of a valid application. For example, if an application is received on 24 August and the assessor validates the submission on 28 August, the clock starts on 29 August.

During the assessment, experts will assess the safety and performance of your device as well as the design of the clinical investigation to be carried out. We will write to you if we require further information. It is essential that you contact us as soon as possible if you require clarification.

If there are possible grounds for objection, where possible we will arrange a teleconference for a better understanding and to find a resolution within the 60-day assessment time.

We will send you a letter by the 60th day with a decision (‘objection’ or ‘no objection’) whether or not you can carry out the proposed clinical investigation.

Applications for an investigative medicinal product and medical device - Parallel Review

This application pathway applies to clinical studies which are both a Clinical Trial of an Investigational Medicinal Product (CTIMP) and a Clinical Investigation (CI) of a medical device.

Where this scenario arises, studies should be submitted to MHRA as a “Parallel Review” application (formerly known as a combined trial of an investigative medicinal product and an investigational medical device (IMP+Device)).

Please see the latest guidance available here: Parallel Review External Guidance (PDF, 281 KB, 8 pages)

The pathway is intended to bridge the gap between two separate sets of legislation, legislative timescales and system functionality.

In the long term, MHRA Clinical Investigations and Trials Unit’s intention is to align regulations and processes as much as possible to create a streamlined submission experience for Parallel Review studies.

Please also see the latest guidance on clinical trials: Medicines: clinical trials hub - GOV.UK

Amendments

This section concerns clinical investigations conducted in Great Britain only. See the separate section below for studies involving Northern Ireland.

Once you’ve received a letter of no objection from us, you must notify us of all proposed amendments to the investigation. You must wait until we send you another letter of no objection before you make the changes.

You must tell us about any changes made to:

the device under investigation
study documentation, including the clinical investigation plan
investigators or investigating institutions
changes requested by an ethics committee

If you do not tell us about proposed amendments, you could be liable to prosecution.

Begin your amendment submission on HRA IRAS.

Refer to the IRAS user guide’s section on amendments.

When you notify the MHRA of amendments, include the following:

a covering letter with the MHRA reference number for the clinical investigation (for example, CI/2023/XXXX)
a table with a summary of each proposed change with the justification for each change
red-lined (showing changes being made) and clean copies of all amended study documentation
a signed statement by, or on behalf of, the manufacturer that the proposed change(s) do not predictably increase the risk to the patient, user or third party

If you do not follow the guidance above, the submission will be returned to you.

Email the amendments to CI-amendments@mhra.gov.uk, unless the files are too big, in which case contact us at the same email address to request a link for uploading the documents. We will only process amendments submitted to this mailbox. Do not submit amendments to individuals or any other mailbox.

Payment for an amendment

Under the new fees implemented in July 2025 there is no fee payable for any amendment to a clinical investigation.

Reporting requirements

Serious adverse event (SAE) reporting

This section concerns clinical investigations with sites in Great Britain, and clinical investigations with sites in both Great Britain and Northern Ireland. Please see the separate section below for studies with Northern Ireland sites only (no sites in Great Britain).

In line with UK Regulations and MEDDEV 2.7/3, all reportable events must be fully recorded and notified to the MHRA. This includes all serious adverse events, irrespective of whether the device has been assessed as having a causal relationship, and reportable events (per MEDDEV 2.7/3) occurring in third countries in which a clinical investigation is performed under the same clinical investigation plan. These can be provided using either the MEDDEV 2.7/3 SAE reporting table, or the MDCG 2020-10/2 SAE reporting table, as long as the required information is included.

Please submit an SAE reporting form in the new MORE portal with your completed table attached.

See details on how to register for the MORE portal.

MEDDEV 2.7/3 also contains further guidance on clinical investigation reporting in Great Britain.

Quarterly summary reports (QSR)

As a condition of MHRA approval for a clinical investigation, in addition reporting individual serious adverse events as detailed above, you must send us quarterly summary reports providing an update on the latest overall safety profile for the investigation.

If the study is UK only, we expect the first QSR to be submitted one quarter after the first participant has been treated.

For studies that also have EU and global sites please provide a QSR one quarter after MHRA approval of the UK study. The report should detail the overall safety profile for ALL study sites.

To provide these summaries, use Quarterly Summary Reports – guidance and template for manufacturers / sponsors (PDF, 375 KB, 6 pages). This template is for devices only but you should also use it for device-related reporting on any combined studies. Do not include detail on any investigational medicinal product (IMP) under investigation.

Submit your quarterly summary reports directly through the MORE portal

Further guidance on submitting SAEs and QSRs on MORE can be found in the MORE Submissions - user reference guide.

Study deviations

Sponsors must notify the MHRA of all deviations (relating to UK study sites only) as soon as they are aware of them. Include details about the nature of the deviation, when it occurred, where it occurred, and any proposed corrective and preventative actions.

Use the following MHRA protocol deviation tracker Excel template when reporting deviations and keep this as a ‘live’ document so that new deviations can be added. This enables both the sponsor and the MHRA to have a complete overview each time it is submitted.

Send the completed spreadsheet by email to info@mhra.gov.uk.

Early termination or temporary halt of a clinical investigation

Sponsors must notify us of the early termination of a clinical investigation and provide a justification for the early termination as stated in Regulations 16(11) and Section 29(10) of the UK MDR 2002.

Send a copy of the final written report of a clinical investigation of a device falling within the scope of the UK MDR 2002 (Regulations 16(10) and 29(9)) to CI-applications@mhra.gov.uk.

Sponsors should also notify us of a temporary halt of a clinical investigation.

Send the notifications to info@mhra.gov.uk.

End of study reports

Email your end of study report to CI-applications@mhra.gov.uk.

Northern Ireland

The Northern Ireland Protocol requires Northern Ireland to continue to align with EU rules for devices after 1 January 2021. Therefore, the Medical Device Regulation (EU) 2017/745 (MDR) and the in vitro Diagnostic Medical Device Regulation (EU) 2017/746 (IVDR) will apply in Northern Ireland from 26 May 2021, and 26 May 2022 respectively, in line with the EU’s implementation timeline.

All clinical investigations requiring application to the MHRA (which involve a site in Northern Ireland) must be submitted to the MHRA in line with the requirements of EU MDR 2017/745.

Note: this single application will also cover any sites proposed in Great Britain in addition to site(s) in Northern Ireland for the same clinical investigation.

We have guidance for manufacturers in Northern Ireland.

Does my study require a clinical investigation application?

For clinical investigations involving a site in Northern Ireland, use this flow chart and accompanying guidance to determine if you need to submit an application to the MHRA.

Please note: MHRA has recently published updates to the GB flow chart and accompanying guidance (see links at the top of this page). As part of this work package, the Northern Ireland flow chart and accompanying guidance documents are also under review, and may be updated in due course. Please check this page regularly to remain up to date with latest guidance on this topic.

The following sections provide guidance for these applications and the requirements for amendments and post market studies involving sites in Northern Ireland.

Assessment of CI applications

When we have received your documents and validated them, we will write to you within 10 calendar days to confirm that the application is valid and the assessment has started, or we will let you know if there are any issues. If there are any issues, we will confirm these in writing and provide a 10 calendar day deadline for a response. The assessment will not start until we have received a valid response. If, after receipt of the response, we still consider the application invalid, or the 10 day deadline has expired, we will write to confirm this within 5 calendar days.

Day 1 of the MHRA assessment is taken as being the date that we confirm that we have received a valid application. During the assessment, experts will assess the safety and performance of your device as well as the design of the clinical investigation to be carried out.

Your application will be assessed (and further information may be requested) in accordance with the procedures and timeframes described in MHRA’s guidance for manufacturers (linked at the top of this page). It is essential that you contact us as soon as possible if you need clarification. If there are possible grounds for refusing authorisation, where possible, we will arrange a teleconference for a better understanding and to find a resolution within the assessment period.

We will send you a letter by the final day (or before) with a decision whether or not you can carry out the proposed clinical investigation.

Amendments/modifications

Once you’ve received authorisation from us to conduct the clinical investigation in Northern Ireland, you must notify us of all proposed modifications to the investigation before you make any changes. You must wait until we send you another letter of authorisation before you make substantial modifications. Depending on whether we consult experts, we will send you our decision within 38 or 45 calendar days.

You must tell us about all modifications, but only those considered to be substantial will require authorisation by the MHRA.

Substantial modification includes:

changes to the medical device under investigation
changes to the design or methodology of the clinical investigation, or to background information
changes to the procedures undertaken by participants
changes to the risk/benefit assessment for the study
significant changes to study documentation such as clinical investigation plan, investigator’s brochure, participant information sheets, consent forms, letters to GPs or other clinicians, information sheets for relatives or carers
appointment of a new chief investigator
inclusion of a new trial site (not listed in the original application)
appointment of a new principal investigator at a trial site
planned restart of a study after a temporary halt, if changes have been made to the device or study
a change to the definition of the end of the study
extension of the study beyond the period specified in the application form
any other significant change to the protocol
changes requested by an ethics committee

For non-substantial modifications you only need to notify us to ensure our records are up to date. If upon review of the proposed non-substantial modification, we consider it to be in the substantial category, we will inform the sponsor, and the proposed modification should not take place until an MHRA authorisation is received.

Non-substantial modifications are changes that are unlikely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation and include:

a change of sponsor(s) or sponsor’s legal representative
a change to the insurance or indemnity arrangements for the study
minor changes to the protocol or other study documentation, e.g. correcting typographical errors, updating contact points, minor clarifications
changes to the chief investigator’s research team
changes to the research team at particular trial sites (other than appointment of a new principal investigator)
changes in funding arrangements
minor changes in the documentation used by the research team for recording study data
changes in the logistical arrangements for storing or transporting samples

Reporting requirements

Serious Adverse Event (SAE) Reporting under Regulation (EU) 2017/745

This section concerns clinical investigations with sites in Northern Ireland (but no sites in Great Britain). For studies with sites in Great Britain, or for studies conducted in both Great Britain and Northern Ireland, please see the separate section above.

The reporting requirements of Regulation (EU) 2017/745 apply to these studies.
The sponsor shall fully record all of the following:

any adverse event of a type identified in the clinical investigation plan as being critical to the evaluation of the results of that clinical investigation;
any serious adverse event;
any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;
any new findings in relation to any event referred to in points (a) to (c).

The sponsor shall report, without delay to MHRA, all the following:

any serious adverse event that has a causal relationship with the investigational device, the comparator or the investigation procedure or where such causal relationship is reasonably possible;
any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;
any new findings in relation to any event referred to in points (a) and (b).

Reports can be provided using the MDCG 2020-10/2 SAE reporting table.
Please submit an SAE reporting form in the MORE portal with your completed table attached.

See details on how to register for the MORE portal.

MDCG 2020-10 also contains further guidance on clinical investigation reporting for Northern Ireland.

For enquiries please see the above section of this guidance page.

Early termination or temporary halt of clinical investigation

Sponsors must notify the MHRA of the temporary halt or early termination of a clinical investigation and provide a justification within 15 days, or 24 hours if the decision was taken on safety grounds. The clinical investigation report and summary must be provided within 3 months for such studies that are temporarily halted or terminated early.

Post market studies

You must notify us of all clinical investigations conducted in Northern Ireland involving CE marked devices that also involve procedures additional to the normal conditions of use of the device, that are also invasive or burdensome.

You must make the notification at least 30 days before starting the study.

When you notify us of these clinical investigations, we need the following information:

application form
investigator’s brochure
clinical investigation plan or protocol
signed statement
REC opinion
proof of insurance cover or indemnification of subjects
PIS and IC
arrangement to ensure protection and confidentiality of personal data
details of the technical documentation (risk analysis, test reports) kept available

Submit your application electronically using the Integrated Research Application System (IRAS).

Medical devices: clinical investigations and performance studies in Northern Ireland

Information about changes to the operation of certain clinical investigations and performance studies in Northern Ireland.

Certain clinical investigations and performance studies that take place in Northern Ireland require the sponsors to be established either in Northern Ireland or the EU or to have a legal representative established in Northern Ireland or the EU.

The rules that apply (Medical Device Regulation (Regulation 2017/745) (MDR) and In Vitro Diagnostics Regulation (Regulation 2017/746) (IVDR) allow the UK to disapply these rules.

This requirement applies if the investigation or study is only taking place in its territory and not in the EU. Therefore, the MHRA is disapplying the requirement for the sponsor or their legal representative of a clinical investigation or performance study to be established in Northern Ireland or the EU, provided all of the following conditions are met:

the investigation or study must also be taking place in both Northern Ireland and Great Britain
the investigation or study must not be taking place in an EU member state
the sponsor must be either established in or have a written agreement with a legal representative in Great Britain, who is responsible for ensuring compliance with the sponsor’s obligations in the MDR or IVDR
the sponsor must establish a contact person in Northern Ireland for the clinical investigation or performance study, who will be the addressee for all communications with the sponsor provided for in MDR or IVDR
any communication with that contact person is deemed to be communication with the sponsor

All remaining requirements under the MDR and IVDR apply. This guidance will take immediate effect.

For guidance on submitting performance studies to MHRA under IVDR, please see IRAS guidance on IVDs and Northern Ireland.

For further information, contact the MHRA info@mhra.gov.uk.

Health Research Authority (HRA) and Health and Care Research Wales (HCRW) Approval

HRA and HCRW approval applies to all project-based research taking place in the NHS in England and Wales. It brings together the assessment of governance and legal compliance, undertaken by dedicated HRA and HCRW staff, with the independent Research Ethics Committee (REC) opinion provided through the UK Research Ethics Service.

It replaces the need for local checks of legal compliance and related matters by each participating organisation in England and Wales. For information on how to prepare and submit an application for HRA and HCRW Approval, refer to the HRA website.

More information

For more details on classifications, see MEDDEV 2.4/1 for guidance on classifications.

For more guidance on Clinical Trials of Medicinal Products (CTIMPs) see: Clinical trials and investigations - GOV.UK.

If you have any questions before submitting your notification, email info@mhra.gov.uk.

Clinical investigations for medical devices