Dear members, following our feedback to the MHRA, on August 22nd the Clinical Trials Guidance page on gov.uk was updated. The update includes specifics of trial submission when companion diagnostics are involved in GB. Separate IVDR related guidance applies to trials conducted in Northern Ireland.
Thanks to Alison Gillies, Leica Biosystems who spotted and reported the update, which I don’t think has otherwise been highly advertised, and highlights the need to refer to the latest updated guidance on gov.uk
Clinical trials for medicines: apply for authorisation in the UK. (Link)
Of note, in addition to the tabular summary to be included, a completed checklist should also be completed and submitted for CTIMPs involving an IVD device with sites in Great Britain. This additional checklist includes e.g. IFU, specimen handling, results recording, instrument validation summary report for each instrument used in the clinical study, lab accreditation details etc etc.
Note: see the rest of page regarding the specifics of the submission via the updated pathway in IRAS reflecting the new clinical trials regulation.
Specifically Required are:
In Vitro Diagnostic (IVD) Devices including Companion Diagnostic Devices
Please identify in the covering letter of your Clinical Trial Authorisation (CTA) application that your clinical trial includes the use of an IVD device including companion diagnostic devices. Submit this information via the Integrated Research Application System (IRAS) under the combined review process.
An in vitro diagnostic device is a medical device which —
(a) is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment or system, whether used alone or in combination; and
(b) 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:
- concerning a physiological or pathological state,
- concerning a congenital abnormality,
iii. to determine the safety and compatibility of donations, including blood and tissue donations, with potential recipients, or
- 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:
(a) identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or
(b) 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.
IVD devices including companion diagnostic devices may be used in clinical trials of medicinal products (Clinical Trials of Investigational Medicinal Products (CTIMPs)) to stratify patients for inclusion/exclusion in the trial or stratified to a cohort within a trial. IVD devices including companion diagnostic devices may be used in 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.
Applicants must submit the following:
(a) If using a UKCA or CE marked device as intended by the manufacturer, the clinical trial 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). This must be submitted with the clinical trial application through IRAS.
(b) 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. This must be submitted with the clinical trial application through IRAS.
(c) If no UKCA or CE marked device is available or the health institution exemption does not apply, the MHRA requests the following items.
Please submit the information for i. OR ii. AND iii.
- If the analytical performance study has been conducted, submit the analytical performance summary report(s) for the IVD device including companion diagnostic devices, demonstrating evidence of device performance. The MHRA will assess the analytical performance to ensure the device is suitable for the clinical trial. The MHRA will issue a decision letter with the outcome.
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
iii. 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.
The MHRA will review the application provided and may request additional information.
The clinical trial applicant should respond fully to one round of question(s) issued in a Grounds for Non-Acceptance letter, within 14 calendar days from receiving the request for information. The MHRA will assess the information and provide a final outcome. If no response is received within 14 calendar days, the clinical trial application will be rejected.
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.
Clinical trials which subsequently determine the clinical performance of the IVD device including companion diagnostic devices should be registered.
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.
