Clinical trials for medical devices

This page provides guidance on how to notify the MHRA. Please see the links at the bottom of this page to guidance documents contained on this website.

Prior to submitting a notification to the Competent Authority, you are advised to ensure that you have the information necessary to demonstrate compliance with all the relevant essential requirements except for those that are the subject of the investigation. A significant percentage of the grounds for objection that have been raised have resulted from the failure to supply the necessary data within the 60 day time period allowed by the Regulations. Details of the information required can be obtained by sending for our Guidance Document pack. This information contained in the pack is also available on the web site. You can now prepare your notification to MHRA online in the Integrated Research Application System (IRAS). IRAS is a UK-wide system that streamlines the process for applying for permissions and approvals to conduct health and social care research, including clinical investigations of medical devices. It allows researchers to enter the information for the relevant permissions and approvals once, instead of having to complete several separate application forms for each review body. Filters are used to ensure that data is collected and collated appropriately to the type of study and the approvals and permissions required. IRAS captures the information needed by MHRA offering the facility for researchers to print out the completed PCA1 and PCA2 forms for signing before making a notification to MHRA in the usual way.

We are happy to answer any questions that you may have about the UK regulatory process for clinical investigations, prior to making a notification, however, we are not able to perform a full assessment of your proposed clinical investigation protocol at this stage. You are therefore advised to contact us should you have any concerns prior to making a notification. Questions should be directed to Daniella Smolenska at daniella.smolenska@mhra.gsi.gov.uk or by telephone on 020 7084 3363.

In some cases, where specific issues cannot be addressed in writing, it may be considered that a pre-submission meeting or conference call is necessary, and we will be happy to arrange such a meeting if required.

Fees
The following charges apply for the pre-clinical assessment of clinical investigation notifications by MHRA, with the fees for re-notification in the event of an objection given in brackets:

Class I, IIa, or IIb other than implantable or long-term invasive: £3,000 (£2,100).
Class IIb implantable or long-term invasive, Class III, and active implantable: £4,100 (£2,700).

Details on how to make payments are in our Bank account section.

Notification process
The processing of the clinical investigation by the Competent Authority is carried out according to the diagrams on pages 24 and 25 of Guidance Note 1.

If further information is required during the course of the clinical investigation assessment, a letter will be sent to the manufacturer. Should the nature of the requested information be unclear to you, it is essential that you contact the Competent Authority as soon as possible and request clarification or a meeting, conference call or video conference if preferred. Please bear in mind that the Competent Authority has a maximum of 60 days to reach a decision. The clock does not stop when additional information is requested. The current Agency target is to process clinical investigations in an average time of 54 days.

If the final letter raises grounds for objection, the reason for these objections will be set out in details as an attachment to the regulatory letter. If you require clarification or any of these reasons, you are advised to discuss them with the Competent Authority prior to making a resubmission. When making a re-submission, manufacturers are advised to detail all changes made between the original and the re-submission, the reasons for these, and their effect on the risk assessment. In addition a statement is required from the manufacturer declaring that the protocol remains unchanged except for those aspects noted in the re-submission application. This will enable MHRA to process the re-submission with the minimum of delay.

Please note that regulation 16 (3) of the Medical Devices Regulations 2002 (No 618) allows notification to the UK Competent Authority at the same time as a submission to the Multi-Centre Research Ethics Committee (MREC)/Local Research Ethics Committee(s) (LREC). This can be facilitated by using the Integrated Research Application System (IRAS). However, a clinical investigation may only begin at a particular centre once the manufacturer has received both a letter of no objection from the Competent Authority and the agreement of the MREC/LREC for the clinical investigation to proceed at that centre. Requirements for obtaining Ethics Committee approval and for obtaining approval for an additional participating centre, have recently changed.

Full details and specific guidance for applicants can be obtained from the National Research Ethics Service (NRES):
› Applying for ethical review (external link)

There is also guidance for applicants for medical device research:
› Medical Devices Guidance (external link)

If you require further advice please email NRES Queries Line on queries@nationalres.org.uk.

More information is also available on the Integrated Research Application System website (external link).

The Competent Authority will try to do everything it can to make this as smooth a process as possible but this will be helped greatly by the Competent Authority receiving all the required and necessary information at the time of the initial submission.

Further information and advice may also be available at the Association of British Healthcare Industries (ABHI) website http://www.abhi.org.uk (external link).

Guidance documents
Further information may be found in the following Guidance Notes:

• Guidance Note 1 - Guidance Notes for manufacturers on clinical investigations to be carried out in the UK
• • Form PCA1
  • Form PCA2
• Guidance Note 3 - Information for clinical investigators
• Guidance Note 5 - Guidance on biocompatibility assessment
• Guidance Note 17 -  Guidance Notes for manufacturers on statistical considerations for clinical investigations of medical devices

model Clinical Investigation Agreement (mCIA)
A model Clinical Investigation Agreement (mCIA) which is designed to be used without modification for company-sponsored commercial research involving medical devices in patients in hospitals throughout the UK Health Service was launched on 6 November 2008.

Versions of the agreement for use throughout the UK and guidance notes are all available on the UKCRC website (external link).

Clinical investigations and health care establishments
We have received a number of enquiries relating to the implications of the clinical investigations provisions of the Medical Devices Regulations 2002 ("the Regulations") for health care and related institutions. We are therefore setting out some guidance in relation to this area. This guidance is of a general nature only and cannot be taken to be a definitive statement of the law. Where there is any doubt, you should always seek your own legal advice.

With regard to the obligations of health care establishments and related organisations generally under the Regulations, Bulletin 18 sets out further information. Guidance Note 1 (Guidance for Manufacturers on Clinical Investigations to be Carried out in the UK) sets out detailed guidance in relation to clinical investigations. Both of those publications should now be read subject to this note.

Ordinarily, a manufacturer will carry out a clinical investigation as part of the process of obtaining a CE marking for a medical device i.e. to demonstrate that the device complies with the essential requirements. Where a medical device is made available for the purposes of a clinical investigation, the manufacturer or his authorised representative must comply with the notification provisions and the clinical investigation must be carried out in accordance with the relevant Directive (see Regulation 16 for general devices and Regulation 29 for active implantable devices). A clinical investigation is an investigation to determine (a) whether the performance of a device conforms to the performances intended by the manufacturer and is designed, manufactured and packaged in such a way that it is suitable for one of more of the functions referred to in the definition of medical device and (b) to determine any undesirable side-effects, under normal conditions of use and assess whether those side-effects constitute acceptable risks when weighed against the intended performance of the device.

We have identified a number of scenarios, which are arising in practice for health care and related establishments. We have set out our view of the legal obligations arising in each of those scenarios below.

1. A health care establishment manufactures a medical device and sees the possibility of placing that device on the market e.g. selling it to another legal entity for commercial purposes. Because the device is to be commercialised i.e. placed on the market, it will need to comply with the provisions of the Regulations. In order to demonstrate conformity with the relevant essential requirements, it may be necessary for the health care establishment to carry out a clinical investigation. Any clinical investigation must be notified in accordance with the Regulations, even if it is carried out on patients of that health care establishment.

2. A health care establishment uses a device for a purpose not intended by the manufacturer (as stated in the data supplied by the manufacturer, on the labelling, instructions for use and/or the promotional material), without the knowledge of the manufacturer. Generally, a health care establishment will not be treated as a manufacturer of a device for the purposes of the Regulations merely because it uses that device for a purpose not intended by the manufacturer. Similarly, where a health care establishment used a device for a purpose other than that stated by the manufacturer on a trial basis, we would not treat that as a clinical investigation. However, there might be other legal consequences following from such action. Also, if the action taken by the health care establishment involved modification of the device, it is possible that the health care establishment might become the manufacturer of a new device and on that basis would be expected to notify us of any clinical investigation carried out with a view to commercialisation of that device (see scenario 1 above).

3. A health care establishment trials a device already on the market with regard to a new purpose (i.e. not intended by the manufacturer as stated in the data supplied by the manufacturer, on the labelling, instructions for use and/or the promotional material) and the manufacturer is involved in that process. Where a manufacturer is seeking to investigate using a new use for a device already on the market, with a view to CE marking the device for that purpose, we consider that the clinical investigation provisions are likely to be engaged. Whether or not that is the case will depend upon the circumstances, including the extent of the manufacturer's involvement and the nature of the trial. It is possible that some very preliminary investigations may not amount to a clinical investigation, but we envisage that the circumstances in which this will occur will be very limited.

4. A health care establishment is asked by a manufacturer to trial a medical device which is not yet on the market. Where a manufacturer is seeking to investigate the clinical potential of a new device that has not yet come onto the market, we consider that the clinical investigation provisions are likely to be engaged.

Any queries regarding this document or the clinical investigation procedure should be addressed to:

Daniella Smolenska
MHRA
Market Towers
1 Nine Elms Lane
London SW8 5NQ

Tel: 020 7084 3363