Guidance

Notify the MHRA about a clinical investigation for a medical device

How to notify the MHRA of your intention to carry out a clinical investigation for medical devices.

You may need to carry out a clinical investigation as part of the process to obtain a UKCA / CE / 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.

How to notify the MHRA of your clinical investigation

A notification to the MHRA will not be required for medical devices that are UKCA / CE / CE UKNI marked for the purpose that is under investigation.

If possible, please provide the MHRA with advanced notice of your intention to submit a clinical investigation by emailing devices.regulatory@mhra.gov.uk with some basic details about the investigational device, the intended population, the type of study, and estimated application date. Please provide as much notice as possible. An advanced notice is helpful to the MHRA, however is not a substitute for the formal clinical investigation notification.

You need to prepare your documents before you notify the MHRA of a proposed clinical investigation.

MHRA guidance

Follow the guidance on compiling a submission (PDF, 258KB, 15 pages) and guidance for manufacturers when preparing your notification application.

Applications are submitted electronically using the Integrated Research Application System (IRAS)

See information for clinical investigators (PDF, 162KB, 8 pages) for what is required by clinicians involved in the investigation.

Check the information on the biological safety assessment (PDF, 172KB, 7 pages) for the scientific data you must submit.

Check statistical considerations (PDF, 173KB, 13 pages) for presenting statistical information for your clinical investigation.

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

See the guidance on UKCA markings.

Fees

The Medical Devices (Fees Amendment) Regulations 2017 came into force on 1 April 2017. These regulations include the introduction of new fees for amendments to clinical investigations.

You do not need to attach proof of payment to applications. You will receive an invoice to allow you to make payment for the correct amount once your application has been validated.

Information on how to notify the MHRA about an amendment for a clinical investigation can be found below under Amendments. Information on the applicable fees are available using the link below.

Please note: The fee rate is based on a single investigational device being used in a study. Where two or more investigational devices are being used and there is no functional relationship between them, the fee will be increased to reflect the additional workload to the MHRA. For further clarification, contact devices.regulatory@mhra.gov.uk

See fees for clinical investigations and make a payment to the MHRA for your notification before submitting it if you haven’t already.

Assessment

When the MHRA has received your documents and validated them, we will write to you within 5 working days to confirm that the 60-day assessment has started or we will let you know if there are any issues. If there are any issues raised, the 60-day assessment will start when we receive a valid response. Day 1 of the 60 days is taken as being the first working day that follows the date of receipt of a valid Notification.

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. The MHRA will write to you if we require further information. It is essential that you contact the MHRA as soon as possible if you require clarification. Where possible we will arrange a teleconference for a better understanding and to find a resolution within the 60-day assessment time, if there are possible grounds for objection.

A letter will be sent to you by the 60th day with a decision (‘objection’ or ‘no objection’) as to whether or not you can carry out the proposed clinical investigation.

Coordinated assessment pathway pilot

The MHRA is working with the Health Research Authority (HRA) to pilot a new coordinated assessment pathway which will streamline the review of clinical investigations involving medical devices.

During this phase of the pilot, the MHRA Medical Devices review and the Research Ethics Committee (REC) review will be done in parallel and information will be shared. There will be no change to the application forms or method of submission.

Taking part in the pilot

If you are interested in taking part in the pilot, you first need to tell us by emailing Devices.Regulatory@mhra.gov.uk with “MHRA/HRA Coordinated assessment pathway pilot” in the subject line. This should be done before submitting any applications and we will then send you further guidance.

For your study to be eligible for the pilot:

  • the lead site should be in England
  • you should contact the MHRA prior to any submission to REC or MHRA

For this phase of the pilot there are some exclusions. We cannot include clinical investigations that:

  • involve participants who are adults lacking capacity
  • are a combined trial of an investigational medicinal product and an investigational medical device

Amendments

Once you’ve received a letter of no objection from us, you must notify the MHRA of all proposed amendments to the investigation. You must wait until we send you another letter of no objection before you implement 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 don’t tell us about proposed amendments you could be liable to prosecution.

When you notify us of amendments, we need the following information:

  • covering letter with:
    • the MHRA reference number for the clinical investigation
    • a table with a summary of each proposed change with the reason 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

  • details of who to invoice (full company name, address and registered tax/VAT number)

You can send us the amendments by email unless the files are too big, in which case contact us at devices.regulatory@mhra.gov.uk to request a link for uploading the documents (see Fees above).

You will need to pay a fee for amendments to clinical investigations.

In Vitro Diagnostic Medical Devices (IVDs)

Unless an exemption applies, all IVDs being placed on the market or put into service in the UK are required to have the relevant mark of conformity (UKCA, CE or CE UKNI).

This includes devices used in clinical trials of medicines to stratify patients for inclusion/exclusion in the trial or stratified to a cohort within a trial.

At the time of the clinical trial application, the UKCA / CE / CE UKNI need only be for the analytical performance of the IVD (e.g. detection of a biomarker) and will include reagents, equipment, calibrators, controls and software.

These are likely to be self-certified IVDs under the current medical device regulations.

Trials which determine the clinical performance of the assay (biomarker validity) will need to be registered as IVD performance evaluation studies.

See guidance on in vitro diagnostic medical devices: guidance on legislation.

Special circumstances for healthcare establishments

You don’t need to notify the MHRA 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.

See common scenarios for healthcare establishments (PDF, 89.4KB, 2 pages) which may be relevant to you.

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.

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

Clinical investigation numbers

The following table provides information on the number of valid clinical investigation applications that have been reviewed by year. Of these, the number withdrawn by the applicant before MHRA issued a decision, and the number objected to along with the most common reasons for objection, are provided.

Year Completed review Withdrawn by applicants Grounds for objection raised Common reasons for objection
2019 58 6 15 Insufficient evidence provided to demonstrate the appropriate biological safety, clinical or technical effectiveness of the device or poor study design
2020 49 6 9 Insufficient evidence of biological safety, sterilisation and software testing
Published 18 December 2014
Last updated 24 March 2021 + show all updates
  1. Added information on the number of valid clinical investigation applications that have been reviewed by year.

  2. A new statistical considerations PDF has been added to reflect the end of the Brexit transition period

  3. Updated biological safety assessment pdf

  4. Added revised information about Health Research Authority (HRA) and Health and Care Research Wales (HCRW) Approval. Also added new information about the Coordinated assessment pathway pilot.

  5. This page has been updated due to the end of the Brexit transition period.

  6. This page has been updated due to the end of the transition period

  7. Updated with a message around amendments over the 2020 Christmas period.

  8. Added information about how the MHRA will review clinical investigations submitted before 26 May 2020, and on or after 26 May 2020.

  9. Published an updated version of the 'guidance for manufacturers'.

  10. We have added in a Christmas period notice for 2019.

  11. The Biological Safety Assessment PDF has been updated.

  12. Added a link to new guidance on medical devices regulation in a no deal scenario.

  13. Updated page - new wording and Guidance attachments

  14. Inserted advanced notice of a change section

  15. Information about rules of processing notifications about clinical investigations by MHRA during period of Christmas 2018

  16. New version of guidance for manufacturers published

  17. Changed MHRA address.

  18. Update to recent changes section

  19. New heading "Upcoming changes"

  20. Added information about the IRAS forms and about providing MHRA with advanced notice of your intention to submit a clinical investigation.

  21. Added note to provide MHRA with advanced notice of your intention to submit a clinical investigation.

  22. Information on processing times over the Christmas 2017 period added to the page.

  23. New 'statistical considerations' document added to the page.

  24. New section about IVDs added to the page.

  25. Updated guidance document

  26. Information about new requirement to pay fees for amendments published

  27. Updated guidance

  28. Added information about Christmas period 2016

  29. Added clarification around the start of the 60-day assessment timeframe.

  30. Information on Health Research Authority Approval

  31. Updated guidance for manufactures on legislation for clinical investigations of medical devices.

  32. First published.