Clinical trials that include an in vitro diagnostic device
Guidance on submitting an application for approval of a clinical trial that includes an in vitro diagnostic device
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Definitions
An in vitro diagnostic device (IVD) is a medical device which —
- is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment or system, whether used alone or in combination; and
- is intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information:
i. concerning a physiological or pathological state,
ii. concerning a congenital abnormality,
iii. to determine the safety and compatibility of donations, including blood and tissue donations, with potential recipients, or
iv. to monitor therapeutic measures,
and includes a specimen receptacle but not a product for general laboratory use, unless that product, in view of its characteristics, is specifically intended by its manufacturer to be used for in vitro diagnostic examination.
A companion diagnostic device is an IVD device, which is essential for the safe and effective use of a corresponding medicinal product to:
- identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; 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 medicinal product.
Further information can be found in the Guidance on the regulation of IVD medical devices in GB.
Using IVDs in a clinical trial
IVD devices, including companion diagnostic devices, may be used in clinical trials of medicinal products (CTIMPs) to stratify patients for inclusion/exclusion in the trial or stratified to a cohort within a trial.
For CTIMPs involving an IVD device with sites in Great Britain:
- IVD devices including companion diagnostic devices must bear a UKCA or CE mark for use as intended by the manufacturer in a clinical trial.
- A health institution exempted device may be used if the IVD device including companion diagnostic devices will be manufactured and used within the same health institution and either on the premises of their manufacture or on premises in the immediate vicinity without having been transferred to another legal entity.
- Where no device that bears the UKCA or CE marking is available for the clinical trial or a health institution exemption does not apply, an analytical performance study should have been conducted prior to the start of the use of the IVD device including companion diagnostic devices with the clinical trial. However, where no analytical performance study has yet been conducted, the characteristics of the IVD device including companion diagnostic devices must be studied. The Tabular Summary that describes the intended performance characteristics of the IVD device or companion diagnostic devices, will be accepted by the MHRA.
This guidance applies to clinical trial sites in Great Britain and includes trials where patient samples are tested outside the United Kingdom, but where the results are used in patient management decisions in Great Britain. This guidance does not apply to clinical trials where the results are not used to make patient management decisions in Great Britain. Patient management decisions will include but are not limited to stratification, selection of participants and randomisations into arms of a clinical trial study. For CTIMPs involving an IVD device for performance studies in Northern Ireland, please refer to published guidance on regulation of medical devices in Northern Ireland.
Clinical trials which subsequently determine the clinical performance of the IVD device including companion diagnostic devices should be registered.
Applying for approval of a clinical trial that includes an IVD device
Applications for approval of a clinical trial that include an IVD device follow the standard approvals process. However, the applicant will need to submit additional information about the IVD device through the Integrated Research Application System (IRAS) as part of the application package.
First, the applicant should identify in the covering letter of the application that the clinical trial includes the use of an IVD device.
The covering letter and/or protocol should also confirm that any applicable CE marking requirements have been complied with (or will be complied with prior to the study start).
In addition:
- if using a UKCA or CE marked device as intended by the manufacturer, the applicant should submit, on a company letterhead, a confirmation that identifies the device manufacturer, their UK responsible person (if applicable) and MHRA device registration on the Public Access Registrations Database (PARD)
- if the clinical trial site in GB is using a health institution exempted device, the clinical trial applicant should submit, on a company letterhead, a confirmation that includes the UKAS accreditation schedule to ISO 15189 and identifying the device(s) on the schedule
- If no UKCA or CE marked device is available or the health institution exemption does not apply, the MHRA requests either:
- If the analytical performance study has been conducted, submit the analytical performance summary report(s) for the IVD device(s), demonstrating evidence of device performance*. The MHRA will assess the analytical performance to ensure the device is suitable for the clinical trial
OR
- if no analytical performance study has yet been conducted at time of application, a Tabular Summary (MS Word Document, 35.5 KB) should be submitted. This document is a description of the analytical methods including acceptance limits and parameters for performing validation. The MHRA will assess the tabular summary and will issue a decision letter with the outcome. Please supply the contents requested without modifying the structure of the template.
AND
- the completed checklist (MS Word Document, 49.3 KB)
*Analytical performance means the ability of the device to correctly detect and/or measure a particular analyte. Analytical performance study refers to technical test performance, which may include data to demonstrate accuracy (derived from trueness and precision), analytical sensitivity (e.g. limit of detection, limit of quantitation), analytical specificity, linearity, cut-off, measuring interval (range), carry-over, as well as determination of appropriate specimen collection and handling, and endogenous and exogenous interference on the results.
Once the application is received, the MHRA will review the application as described in Applying for approval for a clinical trial. Please be aware that if the MHRA issues a request for further information and no response is received from the applicant within 60 calendar days (or a longer period, if an extension is agreed with MHRA), the clinical trial application will be rejected.