Research involving an in vitro diagnostic (IVD) medical device

This guidance sets out what submissions are required for in vitro diagnostic medical device performance evaluation studies which are being undertaken in Northern Ireland. Please note, this guidance applies to new applications only and not the addition of Northern Ireland to an ongoing study. 

In vitro diagnostic (IVD) medical devices are tests used on biological samples (such as tissues, blood or urine) to determine the status of a person's health. This may be a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment or system, whether used alone or in combination. They may be done in laboratories, health care facilities or in the home using a variety of instruments ranging from small, handheld tests to complex laboratory instruments.

The MHRA regulates performance evaluation studies of IVDs in the UK. Currently different regulations apply for studies involving IVD devices taking place in Northern Ireland (NI) compared to those in Great Britain (England, Scotland and Wales).

We strongly recommend, before starting your application, that you familiarise yourself with the relevant regulations that apply to your research.

In Great Britain the Medical Devices Regulations 2002 (UK MDR 2002) apply to IVD research. You can find more information on the relevant legislation for Great Britain on the MHRA website.

IVD research taking place in NI would fall under EU regulations (EU IVDR). The MHRA provide further guidance on the relevant legislation for NI.

Initially we recommend you review the relevant legislation that apply to your IVD research. If your IVD research will take place in Northern Ireland then the following guidance will help you understand what regulatory submissions you may need to make and how you can do so. 

IVD medical device research taking place in Northern Ireland

Contents:

• Does my IVD medical device performance evaluation study require regulatory submission or notification under the EU IVD Regulations?
• What approvals do I need for my IVD medical device clinical performance evaluation study if it is taking place in Northern Ireland?
• Complying with EU IVDR legislation – how to apply
• Where a full MHRA devices application is needed – IVD medical device is to be used as a companion diagnostic in a Clinical Trials of Investigational Medicinal Products (CTIMP)
• Where a full MHRA devices application is needed – for other IVD medical device research (non-CTIMP)
• Glossary of IVD research terms
• Feedback

Does my IVD medical device performance evaluation study require regulatory submission or notification under the EU IVD Regulations?

An IVD medical device performance evaluation study is considered to be taking place in Northern Ireland if the study is taking place at a site in Northern Ireland and involves tissue samples which come from people who live in Northern Ireland. 

You need to make a regulatory submissions to MHRA Devices, under the EU IVD Regulations, if your study is taking place at a site in Northern Ireland and it involves any of the following:

• a clinical performance evaluation of a companion diagnostic in a CTIMP that is a non-CE/UKCA marked IVD device/assay or a CE/UKCA marked IVD device/assay that:
  • has been modified, or 
  • is being used outside its current CE/UKCA marking/intended purpose
    
    
• a clinical performance evaluation of a non-CE/UKCA marked IVD device/assay which involves:
  • surgically invasive sample taking for the purpose of the study, and/or
  • the IVD test results possibly influencing the clinical management of participants, and/or
  • additional invasive procedures or other risks
    
    
• a clinical performance evaluation of a CE/UKCA marked IVD device/assay that has either been modified or is being used outside its current CE/UKCA marking/intended purpose which also involves:
  • surgically invasive sample taking for the purpose of the study, and/or
  • the IVD test results possibly influencing the clinical management of participants, and/or
  • additional invasive procedures or other risks
    
    
• a post market performance follow up (PMPF) of a CE/UKCA marked device/assay being used within its intended purpose where the investigation would involve procedures additional to those under the normal conditions of use and which are either invasive or burdensome. 

If any of the statements above applies to your research, you can check the application requirements by reviewing the table below.

What approvals do I need for my IVD medical device clinical performance evaluation study if it is taking place in Northern Ireland?

Before starting your application, you should review the table below to understand the requirements for your research:

If you require this table in an accessible format, please make a request to iras.queries@hra.nhs.uk.

Complying with EU IVDR legislation – how to apply

After using the table above, if your research requires submission or notification under EU IVDR, the table will indicate which requirements apply.

If you need to submit a full application to MHRA devices follow the detailed instructions in the relevant section below.

Note: In addition to the requirements in NI, if your research includes other UK nations (England, Wales or Scotland), make sure you’re following the relevant application requirements for that nation too.

Where a full MHRA devices application is needed – IVD medical device is to be used as a companion diagnostic in a Clinical Trials of Investigational Medicinal Products (CTIMP)

Where the table above has indicated that a full application to MHRA devices will be required under EU IVDR - you will need to ensure you apply in the new part of IRAS for the following:

• HRA and HCRW Approval and/or NHS/HSC R&D permissions (if your study involves NHS/HSC sites)
• NHS Research Ethics Service – mention in your cover letter that your research falls under EU IVDR and that you have notified/applied to MHRA devices as required. 
• MHRA Medicines
• MHRA Devices - You’ll need to provide an MDCG application form and a completed Annex XIII part A statement as supporting documents for MHRA devices to review (these documents should be emailed to MHRA Devices: CI-applications@mhra.gov.uk)

Make your application through the new part of IRAS, by following the instructions provided for combined IMP/Device studies.

For any queries regarding how to make a submission via IRAS, contact iras.queries@hra.nhs.uk and use ”IVDR Research Application” in the email subject. Please direct any queries relating to submission or notification requirement or the EU IVD Regulations to CI-applications@mhra.gov.uk.  Please add Northern Ireland to the subject heading of your email.

Where a full MHRA devices application is needed – for other IVD medical device research (non-CTIMP)

Where the table above has indicated that a full application to MHRA devices is needed under EU IVDR, you’ll need to apply in the standard part of IRAS for the following:

• HRA and HCRW Approval and/or NHS/HSC R&D permissions (if your study involves NHS/HSC sites)
• NHS Research Ethics Service –mention in your cover letter that your research falls under EU IVDR
• MHRA Devices - You’ll need to provide an MDCG application form and a completed Annex XIII part A statement as supporting documents for MHRA devices to review (these documents should be emailed to MHRA Devices: CI-applications@mhra.gov.uk)
  

Glossary of IVD research terms

Part A Annex XIII statement - A statement from the manufacturer of an IVD device. Confirming the manufacturer’s commitment reiterating the IVD device conforms to the EU In Vitro Diagnostic Regulation (IVDR) and demonstrating the scientific validity, analytical performance and clinical performance of the IVD device for its intended purpose as stated by the manufacturer.
If your research is in Northern Ireland and any other UK nation you should complete a Part A Annex XIII statement.

Companion diagnostic means an IVD device which is essential for the safe and effective use of a corresponding medicine to identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicine; or identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicine.

Device Online Registration System (DORS) is the electronic system to register medical devices and IVD devices with the MHRA (the UK Competent Authority).

Invasive sample collecting is the removal of samples involving invasive procedures, only for the purpose of the study. This would include procedures such as obtaining biopsies during surgical or endoscopy procedures and blood draws.

Left over samples are samples removed for a primary reason, such as during the course of treatment, diagnostic procedures, testing or participation in research, and are now being used for a secondary purpose (such as a performance evaluation study of an IVD). If the study is not an interventional performance evaluation study, this also includes samples obtained via non-invasive procedures, such as external collection of urine or faecal samples or external swabs.

MDCG Form – A form created by the Medical Device Coordination Group (MDCG) intended to be completed for IVD performance studies to demonstrate compliance with the EU In Vitro Diagnostic Regulation (IVDR).

Performance Evaluation Study is a study undertaken to establish or confirm the analytical or clinical performance of a device. Analytical Performance means the ability of a device to correctly detect or measure a particular analyte. Clinical performance means the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state in accordance with the target population and intended user.

Interventional clinical performance study – This is a clinical performance study where the test results may influence patient management decisions and/or may be used to guide treatment 

Public Access Registration Database (PARD) is the publicly accessible registry of registered manufacturers and medical devices and IVD devices in the United Kingdom.

Tabular Summary – A document that describes the analytical methods including acceptance limits and parameters for performing validation when the IVD device has not demonstrated analytical or clinical performance. A template of a tabular summary is available on the MHRA website.

Feedback

We are always working to improve the guidance we provide to researchers. To provide feedback on this page and its resources please email: iras.queries@hra.nhs.uk.