Guidance

Notify MHRA about a clinical investigation for a medical device

How to notify MHRA of your intention to carry out a clinical investigation for a CE marking.

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

How to notify MHRA of your clinical investigation

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

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

If possible, please provide 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 MHRA, however is not a substitute for the formal clinical investigation notification.

Required documents

You must submit all relevant documents listed in the Checklist of required documents for clinical investigation notification (PDF, 196KB, 3 pages) as part of your notification.

Print and sign the PCA1 and PCA2 forms on the integrated research application system (IRAS). You’ll need to sign up to IRAS if you haven’t already.

All documents must be labelled as separate attachments on the CDs you submit. Your attachments must:

  • be labelled on the CD in a way which reflects the content
  • be in English
  • have searchable content
  • contain only legible information

Follow the guidance for manufacturers (PDF, 529KB, 30 pages) when preparing your notification application.

Or see guidance on in vitro diagnostic investigations for medical devices (PDF, 133KB, 15 pages) which are regulated as performance evaluations.

Recent changes

Please note that the MHRA application forms changed on 18 April 2018. There is now only one form called Clinical Investigation Application Form. We are in the process of updating our guidance documents. In the meantime they contain references to our old forms (PCA1 and PCA2).

If you started an application on IRAS before 18 April 2018 and were unable to fully complete it before this date, a new MHRA form will need to be reviewed to ensure satisfaction with the data fields that have been transferred from the old form when you next log into IRAS. Contact the IRAS helpdesk if any issues arise.

The new form identifies key aspects of the devices under investigation and the study. This will help ensure relevant information necessary for validation is included in the notification when submitted.

The main changes can be summarised as:

  • significantly more detail about the investigational devices
  • incorporation of sterilisation questions and software questions within one form
  • significantly more detail about the study bringing MHRA and IRAS forms closer into alignment
  • electronic sign off – no longer need to print and sign the form.

Fees

As of 1 April 2017, the way you pay for clinical investigations has changed.

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. Please note that the IRAS forms still have questions relating to payment to MHRA, however you no longer need to pay in advance of making your application.

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.

Information on how to notify 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.

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

Submit your application

You must submit 3 copies of all forms and documents, each on a separate CD. Please submit 1 extra CD for each of the following:

  • where animal tissues have been utilised
  • where the device is patient contacting
  • where non CE marked software is being used (for stand-alone software and all devices that incorporate software)

If your investigation includes these three factors, you will need to submit a total of 6 CDs.

Please include an index on each CD and avoid using several subfolders in your submission.

Annie Dhillon
Regulatory Affairs Manager (Medical Device Clinical Trials)
MHRA
10 South Colonnade
London
E14 4PU

Assessment

When 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. MHRA will write to you if we require further information. It is essential that you contact 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 or before with a decision (‘objection’ or ‘no objection’) as to whether or not you can carry out the proposed clinical investigation.

Amendments

Once you’ve received a letter of no objection from us, you must notify 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 send them on CDs (3 copies, each copy on a separate CD).

As of 1 April 2017, 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 EU are required to be CE marked.

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 CE mark need only be for the analytical performance of the IVD (eg 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.

The question of whether clinical performance studies involving non-CE marked IVDs can take place on a voluntary basis under the IVDR between now and 2022 is subject to further interpretation.

Special circumstances for healthcare establishments

You don’t need to notify 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 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, 71.1KB, 1 page) which may be relevant to you.

Heath Research Authority (HRA) approval

HRA Approval is the new process for applying for approvals for all project-based research in the NHS led from England and replaces previous systems including the NIHR Coordinated System for gaining NHS Permission (CSP).

HRA Approval brings together the assessment of governance and legal compliance, undertaken by HRA, with the independent 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.

More details about how to apply, how to open new sites for pre-HRA Approval studies, and how to submit amendments for all studies where the lead NHS R&D office is in England can be found here

More information

See information for clinical investigators (PDF, 129KB, 10 pages) for what is required by clinicians involved in the investigation.

Check the information on the biological safety assessment (PDF, 107KB, 7 pages) for the scientific data you must submit.

Check guidance our assessors follow (PDF, 140KB, 10 pages) to see how your notification is assessed.

You can also see statistical considerations (PDF, 189KB, 12 pages) for presenting statistical information for your clinical investigation.

See the guide on CE markings for more details on this and the European Commission’s website for guidance on classifications: Section 2.4 - Classification of MD (June 2010).

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

Published 18 December 2014
Last updated 18 June 2018 + show all updates
  1. Changed MHRA address.
  2. Update to recent changes section
  3. New heading "Upcoming changes"
  4. Added information about the IRAS forms and about providing MHRA with advanced notice of your intention to submit a clinical investigation.
  5. Added note to provide MHRA with advanced notice of your intention to submit a clinical investigation.
  6. Information on processing times over the Christmas 2017 period added to the page.
  7. New 'statistical considerations' document added to the page.
  8. New section about IVDs added to the page.
  9. Updated guidance document
  10. Information about new requirement to pay fees for amendments published
  11. Updated guidance
  12. Added information about Christmas period 2016
  13. Added clarification around the start of the 60-day assessment timeframe.
  14. Information on Health Research Authority Approval
  15. Updated guidance for manufactures on legislation for clinical investigations of medical devices.
  16. First published.