Research involving an in vitro diagnostic device (IVD)

In vitro diagnostic medical devices (IVD) are tests used on biological samples (such as tissues, blood or urine) to determine the status of a person's health. 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 evaluations of IVDs in the UK. Currently different regulations may apply for studies involving IVDs 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 applies to your research.

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

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

After reviewing the guidance on the relevant legislation, this page is designed to help researchers understand what’s needed for their IVD research and how to apply.

• IVD Research in Northern Ireland – does EU IVDR apply?
• What approvals do you need for IVD research?
• Complying with EU IVDR legislation – how to apply
• Where a full MHRA devices application is needed – IVD 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 research (non-CTIMP)
• Glossary of IVD research terms
• Feedback

IVD Research in Northern Ireland – does EU IVDR apply?

Research activity is taking place at a site in Northern Ireland and the research involves any of the following:

• Surgically invasive sample taking for the purpose of the study
• The IVD test results may influence the clinical management of participants
• Additional invasive procedures or other risks

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

For applications where only the UK MDR 2002 legislation applies, you should submit your application in IRAS (if required) in the usual way .

What approvals do you need for IVD research?

Before starting your application, 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 falls 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 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 and falls 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
• MHRA Medicines
• MHRA Devices - You’ll need to provide an MDCG application form as a supporting document for MHRA devices to review
  
  You should also notify the MHRA of the study on DORS and upload a completed Annex XIII part A statement.

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

For any queries, contact iras.queries@hra.nhs.uk and use ”IVDR Research Application” in the email subject.

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

Where the table above has indicated that a full application to MHRA devices is needed and the research falls 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 as a supporting document for MHRA devices to review.
  
  You should also notify the MHRA of the study on DORS and upload a completed Annex XIII part A statement .

Follow these steps when applying in standard IRAS:

1. Create a new research project in IRAS.
2. You must ensure that you answer these specific questions on the project filter page as follows:
   a. Q2 - ‘Clinical investigation or other study of a medical device’ option.
   b. Q2a - select ‘Yes’ & ‘Clinical investigation for UKCA/CE UKNI/CE marking purposes (includes investigation of a UKCA/CE UKNI/CE marked device outside its current intended purposes or in modified form)’.
   c. Q4 - the following boxes should be ticked: ‘IRAS Form’ and ‘Medicines and Healthcare products Regulatory Agency (MHRA) Devices Division’.
3. Proceed to complete your application as normal. Make sure to include the completed MDCG form with your supporting documents and mention in your cover letter that your research falls under EU IVDR.

Glossary of IVD research terms

Annex VIII statement – A statement from the manufacturer of an IVD device. This statement confirms that the IVD device conforms to the requirements of the IVD Directive, apart from the aspects covered by the evaluation and apart from those specifically itemised in the statement, and that every precaution has been taken to protect the health and safety of the patient, user and other persons.
If your research is only in Great Britain, you should complete an Annex VIII statement.

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 for the purpose of the study. This would include procedures such as obtaining biopsies during surgical or endoscopy procedures and blood draws which are additional to clinical requirement.

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). 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 of an in vitro diagnostic device refers to a device intended by the manufacturer to be subject to one or more performance evaluation studies in laboratories for medical analyses or in other appropriate environments outside his own premises.

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.