Clinical Trial Authorisations (CTA) – December 2020
Our Regulatory Affairs Team focus on the important information you need, as we approach the end of the BREXIT transition period.
How will Brexit impact my clinical trial?
MHRA has published several updates to the guidance for Clinical Trial Authorisations that Sponsors or their Representatives will need to follow from 01 January 2021. S-cubed has reviewed this guidance alongside the published EU guidance and have summarised the information on the main changes required to both UK and EU CTAs due to Brexit.
Trial Sponsor/Legal Representative Requirements
Currently for UK clinical trials, the Sponsor or Legal Representative (for non-EU Sponsors) can be in the UK or EU. From 01 January, the Sponsor or Legal Representative will be required to be based in the UK or in a country on an approved list, which initially includes EU/European Economic Area (EEA) countries. Thus, for ongoing UK trials where the Sponsor or Legal Representative is in the UK or EU/EEA, no amendments will be necessary.
For trials that have clinical sites within the EU/EEA, where the Sponsor or Legal Representative is in the UK, a substantial amendment should be approved by the relevant EU/EEA competent authorities, to assign a Legal Representative based in the EU/EEA before the end of the transition period.
Submitting an Application to the MHRA
- New CTAs:
The process for submitting a new CTA will be slightly different from the current process although a EudraCT number will still be required for the trial. The two differences will be that the EudraCT Application Form will be replaced with the IRAS (Integrated Research Application System) MHRA Medicines Form and the submission will need to be made using the MHRA’s Submission Portal, instead of CESP. IRAS is currently used for UK Ethics Committee submissions and will require a separate registration, details of which can be found here. The MHRA Submission Portal will be used for all submissions to the MHRA from January and details of the registration process can be found here or you can read our previous update here.
- Ongoing CTAs:
From 01 January, if the information in the CTA Application Form (Annex 1 form) needs to be updated due to an amendment, then the update should be made using IRAS. This can be done by importing the existing EudraCT xml file into the IRAS system. If there are any differences caused by the changeover these can be explained in the amendment form or cover letter.
Public Clinical Trial Registries
Registration of clinical trials on a publicly accessible register is a formal condition of Research Ethics Committee (REC) approval in the UK. From 01 January, information on UK clinical trials will no longer be uploaded to the EU Clinical Trials Register. Sponsors should therefore register new UK clinical trials with other existing established international registers to ensure information on a clinical trial is publicly available, e.g. ISRCTN Registry or ClinicalTrials.gov. The timelines for registering the clinical trial remain unchanged; registration should ideally occur before the first participant is recruited and no later than six weeks after recruitment of the first participant (unless the study qualifies for deferral).
For ongoing clinical trials that have both UK and EU sites (with the exception of Phase 1 studies in adults) where there will still be a record in the EU Clinical Trials Register, the MHRA will accept publication in EudraCT for trials that have been registered prior to 01 January without the need to transfer the study to another publicly available register.
Investigational medicinal product (IMP) batch certification and importation
Currently, IMP batch certification and importation for UK or EU clinical trials can be undertaken at either a UK or EU site with the appropriate Manufacturer’s Authorisation and any changes to this require submission of a substantial amendment. From 01 January, the requirements will change for both UK and EU clinical trials.
- UK Clinical Trials:
From 01 January, the UK will accept batch certification/importation by UK authorised manufacturers, and also authorised manufacturers from countries on the ‘approved country list’ (initially including EU/EEA countries) such that direct supply to study sites in the UK can continue.
For ongoing UK clinical trials with EU study sites that have a UK site for IMP certification and release, a substantial amendment can be submitted to the MHRA to change to an EU site which can then be used for release of IMP to the trial in both the UK and EU. A substantial amendment to MHRA is not required if an EU site is being added for the EU study sites only.
From 31 December 2021, a UK clinical trial using IMPs imported into Great Britain (England, Scotland and Wales) from a country on the ‘approved country for import’ list will require a UK MIA(IMP) holder to perform an additional check to confirm these IMPs have been certified by the QP in the listed country, before the IMP can be released to the trial in the UK. This means that from 01 January 2021, IMPs can continue to be supplied directly from an EU/EEA MIA(IMP) holder to an ongoing Great Britain trial site without this oversight process taking place, but within a year, a substantial amendment should be submitted to the MHRA to include the relevant details of the MIA(IMP) holder performing the supply chain oversight.
Under the Northern Ireland Protocol, this requirement is only applicable for import into Great Britain from outside the UK, therefore for IMPs coming into Great Britain from Northern Ireland there is no additional oversight required.
- EU Clinical Trials:
From 01 January, the EU will only accept batch certification/importation by authorised manufacturers located in the EU (with the exception of Northern Ireland, where the Qualified Person of a clinical trial can still be established). For ongoing EU trials with a UK site for IMP certificate and release, a substantial amendment should be approved by the relevant competent authorities to change to an EU site prior to the transition period ending.
Publishing Clinical Trial Results
It is currently a requirement that, once a clinical trial is complete, the trial results should be uploaded to the EU Clinical Trials Register within one year of end of trial, or within 6 months for paediatric studies. This time frame for publishing the clinical trial summary report will remain unchanged, and the summary results will need to be published within the public registries that were used for the initial registration of the trial – this will include the EU Clinical Trials Register for CTAs approved before the end of the transition period.
There will continue to be no need to submit the clinical trial summary report to MHRA, however they will still require email confirmation that the results have been published.
It is anticipated that for all UK studies in the EU Clinical Trials Register, the EudraCT system will update the studies with a new status, however, the presence of summary results will be an indication that the study is complete.
Clinical Trial Regulation (EU) No 536/2014
The Clinical Trial Regulation will not be implemented in Great Britain. In Northern Ireland, part of the Regulation will be applicable however, this only relates to Chapter IX concerning the Manufacture and Import of IMPs and Auxiliary Medicinal Products.
Guidance is continuing to be developed and new updates are being routinely published. If you have any questions about how Brexit will affect your clinical trial, then please contact us! And subscribe to our updates here.