Clinical Trials UK Post-Deal Guidance

by
MedicinesUK Post-Deal Published Guidance

Guidance

Registration of clinical trials for investigational medicinal products and publication of summary results

This guidance contains information about registration of clinical trials, publishing trial results and requirements.

Published 31 December 2020
From:
Medicines and Healthcare products Regulatory Agency

Registration of your clinical trial

Actions for those involved in registering clinical trials

You should use existing and established international registers such as ISRCTN registry, or ClinicalTrials.gov, to ensure the public is aware of your trial. For trials involving both UK and EU sites a record in the EU Clinical Trials Register will exist (other than adult Phase 1 studies).

In the UK, any favourable opinion given by a research ethics committee is subject to the condition that the clinical trial is registered on a publicly accessible database. Registration should occur before the first participant is recruited and no later than six weeks after recruitment of the first participant. This has not changed. You should continue to include the registry number, if available, in the Integrated Research Application System (IRAS) when you prepare your application.

If a sponsor wishes to request a deferral of study registration within the required timeframe, in accordance with current transparency rules (e.g. due to commercial sensitivity), they should contact the Health Research Authority (HRA) at study.registration@hra.nhs.uk.

The UK makes information about trials being conducted in the UK available to the public, patients, researchers and clinicians via the HRA research summaries website and UK “Be Part of Research” website.

Publishing trial results

The time frame for publishing the summary of results is within 6 months of the end of trial for paediatric clinical trials or within one year of the end of trial for non-paediatric clinical trials.

Actions for those publishing results

You should publish your summary results within these timeframes in the public register (or registers) where you have registered your clinical trial.

You do not need to submit this clinical trial summary report to the MHRA as well; however, you must send a short confirmatory email to CT.Submission@mhra.gov.uk once the result-related information has been uploaded to the public register and provide a link. If your clinical trial is not on a public register, summary results should be submitted to the MHRA.

You should also submit a final report to the Research Ethics Committee within the same timeframe for reporting the summary of results.

Future requirements

We will communicate further on any longer-term requirements for registration and reporting of trials.

Clinical Trials webinar recording which took place on 21 October 2020:

Contact

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. You can also email clintrialhelpline@mhra.gov.uk with urgent questions. Alternatively, contact your Trade Association by emailing:

Published 31 December 2020

Guidance

Guidance on submitting clinical trial safety reports

How to submit Suspected Unexpected Serious Adverse Drug Reactions (SUSARs) and annual safety reports Development Safety Update Reports (DSURs).

Published 31 December 2020
From:
Medicines and Healthcare products Regulatory Agency

You must submit SUSARs in Great Britain and in Northern Ireland to the MHRA in one of the following ways:

If you intend to submit SUSARs using one of the new reporting routes, you must register.

For trials ongoing in both the UK and in European member states dual reporting is needed. You will need to report each SUSAR to both the MHRA and to the European Medicines Agency’s (EMA’s) Eudravigilance Clinical Trial Module (EVCTM).

Reporting SUSARs using the new reporting routes

Sponsors and Contract Research Organisations (CROs) will need to register to either the ICSR Submissions or the MHRA Gateway to enable configuration of their systems before 1st January 2021 in order to submit SUSARs to the MHRA.

If you have already registered, you do not need to complete this process again.

In order to differentiate SUSAR reports from post-marketing ICSRs, the new reporting systems will enable sponsors and CROs to specify the type of report from a study and assign the study type as a clinical trial.

Registering for ICSR Submissions

The ICSR Submissions is a web reporting tool that will replace the EudraVigilance website (EVWEB). It mimics the same reporting processes by enabling users to complete the online reporting form with details of the SUSAR. It also has the functionality to allow users to upload files that were submitted via the Eudravigilance System. This by-passes the need to complete the form.

The ICSR Submissions route is used to submit single SUSAR reports. To submit SUSARs to the MHRA using this route, visit the ICSR Submissions portal to register. Select ‘Request company account’ and follow the step-by-step guide to gain access to ICSR Submissions in the reference guide Registration for ICSR Submissions.

The ICSR Submissions registration video demo also covers the end-to-end process for registering to use the ICSR Submissions to report SUSARs.

On receipt of your registration request, the MHRA will aim to complete your registration within 5 working days.

Registering for MHRA Gateway

The MHRA Gateway will replace the Eudravigilance Gateway and offers a direct, secure database-to-database transmission of SUSARs into the MHRA system. The MHRA Gateway route is used to submit bulk SUSAR reports.

In order to gain access to, and submit SUSARs via, the MHRA Gateway, you will first need to access and register with another portal called MHRA Submissions.

Registering to MHRA Submissions:

The reference guide Gaining Access to MHRA Submissions provides a step-by-step account of how to set up user access. Guidance on managing users of the portal is also available in the reference guide Managing users on MHRA Submissions.

Three video demos provide further information on the user access management process and user permissions for using MHRA Submissions.

The MHRA Gateway registration video demo covers the end-to-end process for registering to use the MHRA Gateway to report SUSARs.

Direct links to the MHRA Gateway and MHRA Submissions are only provided once reporters are registered.

Reporting SUSARs using the eSUSAR website

We will be retaining the availability of the eSUSAR website for sponsors and CROs who wish to continue reporting SUSARs using this route.

If you currently report SUSARs using the eSUSAR website there is no additional need to register to either the ICSR Submission or the MHRA Gateway to submit SUSARs.

The eSUSAR website route is used to submit single SUSAR reports.

Transition between reporting to EU and UK systems

SUSARs currently reported using either EVWEB or the Eudravigilance Gateway are transmitted to the MHRA via the EMA’s Eudravigilance system.

Sponsors and CROs should plan on the basis that all SUSARs submitted via the Eudravigilance system and processed before 11:00pm on 31 December 2020 will be passed to the MHRA. SUSAR submissions not processed before this point will have to be reported using the new submission routes.

To assist companies in any reconciliation required, the MHRA intends to publish a list of cases received on 31 December 2020 from the EMA. This list will be made available in January 2021.

Business Continuity Plan for MHRA Gateway and ICSR Submissions

The MHRA will communicate at the earliest opportunity the expectations required by sponsors, CROs, and the MHRA when the MHRA Gateway and ICSR Submissions are impacted by planned and unplanned downtime. Please refer to the Business Continuity Plan for further information

Submitting Development Safety Update Reports (DSURs) to the MHRA

You will need to submit DSURs using MHRA Submissions – see the section regarding registration to this system if applicable.

DSURs and Annual Progress Reports (provided in lieu of a full DSUR) should be submitted to the MHRA using MHRA Submissions via the Human Medicines option. Select ‘Development Safety Update Report’ as the Regulatory Activity and ‘Original Submission’ from the Regulatory sub activity dropdown list.

Acknowledgements of receipt for DSUR submissions are generated by MHRA Submissions where a confirmation is emailed to the reporter.

If you are a CRO submitting DSURs on behalf of a trial sponsor, you both need to register to MHRA Submissions. The sponsor should be able to ‘add new organisation with users’ or ‘add user’ for CROs to have access with administrative permissions to make submissions.

For further information refer to registering with MHRA Submissions.

For further information please see our guidance Webinars: preparing to make submissions to the MHRA from 1 January 2021.

Contact us

If you have any queries around setting up the gateway company administrator on MHRA Submissions then please email submissions@mhra.gov.uk.

If you have not received an acknowledgment within 48 hours of submitting a SUSAR, contact E2B.support@mhra.gov.uk, including information on the filename, message number and sender report ID, as well as attaching the XML file.

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. You can also email submissions@mhra.gov.uk with urgent questions.

Published 31 December 2020
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Guidance

Guidance on substantial amendments to a clinical trial

Information about when you need to submit substantial amendments to a clinical trial including changes to the trial sponsor or legal representative, Investigational medicinal product certification and importation.

Published 31 December 2020
From:
Medicines and Healthcare products Regulatory Agency

From 1 January 2021 either the sponsor or the legal representative of a clinical trial must be established in the UK or in a country on an approved country list. This list does include EU/European Economic Area (EEA) countries.

If you need to change the sponsor or legal representative for a UK trial, you must make a submission to both the Medicines and Healthcare products Regulatory Agency (MHRA) and the Research Ethics Committee (REC). This change is a substantial amendment.

Find out more in our guidance.

EU law requires that the sponsor of a clinical trial or a legal representative must be established in the EU. If you need to update your details for an ongoing trial in the EU/EEA then the substantial amendment must be submitted to the EU/EEA competent authorities using your usual method. .
There is no need to submit an amendment to MHRA if:

  • the sponsor or legal representative is established in the EU/EEA
  • the legal representative for a multi-country study is based in the UK and you are updating details via an amendment to other competent authorities
  • the sponsor is established in the UK but a legal representative is added to cover EU/EEA sites via an amendment to other competent authorities.

Investigational medicinal product (IMP) certification and importation

You need to submit a substantial amendment to add or change any IMP manufacturing, importation or certification site relevant for supply of IMP to an ongoing UK trial.

You do not need to submit a substantial amendment if the sponsor retains an existing UK IMP release site for the UK trial and includes an EU/EEA release site for trials in the EU/EEA.

The IMP supply chain from a country on the approved country list will allow direct supply to clinical investigator sites.

If the licence holder needs to be added to a trial

If the holder of a Manufacturer’s Authorisation for IMPs (MIA(IMP)) is required to be included for importation to an ongoing trial, a substantial amendment should be submitted to the MHRA to include the details of the Manufacturer’s Licence (MIA(IMP)) holder performing the ‘supply chain oversight’ role within one year of 1 January 2021.

This means that for up to one year after 1 January 2021, IMPs may be supplied direct from the EU/EEA MIA(IMP) holder to the ongoing Great Britain trial site without the GB MIA (IMP) oversight process.

Amendments relevant to the Research Ethics Committee (REC)

The Health Research Authority (HRA) has produced guidance on when amendments are required to be submitted for REC review.

Northern Ireland Protocol

Guidance on arrangements in Northern Ireland has been published.

Find out more

You can watch a recording of the Clinical Trials webinar which took place on 21 October 2020.

Contact

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. You can also email clintrialhelpline@mhra.gov.uk with urgent questions. Alternatively, contact your Trade Association by emailing:

Published 31 December 2020
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