Currently UK clinical trials are regulated by the EU Clinical Trials Directive, which was transposed into UK law in 2004. In 2014, a new EU Clinical Trial Regulation was agreed that aims to improve clinical trial transparency and simplify the application process for clinical trials across EU member states. This new regulation is expected to be implemented during 2020. If this happens, and the UK secures a deal with the EU, the new regulation would apply under the terms of the implementation period that lasts until 31 December 2020. If the regulation does not come into effect during the implementation period, the UK Government has confirmed its intention to align where possible with the regulation without delay when it comes into force in the EU, subject to the usual parliamentary approvals. In the event of no-deal, the UK Government will re-align with those parts of the regulation that are within its control. The two key elements of the new regulation that the UK would not be able to implement on its own after the withdrawal date are the use of the shared central IT portal and participation in the single assessment model, both of which would require a negotiated agreement between the UK and EU following the implementation period.
On 4 January 2019, and following its consultation in October 2018, the Medicines and Healthcare products Regulatory Agency (MHRA) updated its guidance note on the regulation of clinical trials in the event that there is no Brexit deal. The guidance provides that, in the event of no deal, the MHRA would take on responsibilities to regulate clinical trials for the UK that are currently undertaken through the EU system and proposes that such a UK system would operate as set out below.
The UK will continue to recognise existing approvals – both for regulatory and ethics approvals – and there will be no need to re-apply.
Location of trial sponsor
The UK would require the sponsor or legal representative of a clinical trial to be in the UK or a country on an approved country list, which would initially include EU/EEA countries.
Although in its consultation, the MHRA had proposed the introduction of a UK contact point, following stakeholder feedback, it concluded that a separate registration of a UK contact point is not necessary. If the UK needs to suspend or terminate a trial, the current legislation allows the MHRA to serve the suspension/termination notice on the sponsor or the investigator responsible for the conduct of the trial at the relevant UK sites. However, as set out in the European Commission’s notice to stakeholders, where trials are pan EU, sponsors or legal representatives must be based in the EU.
IMPs for trials
For Investigational Medicinal Products (IMPs) coming into the UK, the UK will recognise Qualified Person (QP) certification undertaken in an approved country, which would initially include all EU and EEA countries. This means that it will not be necessary to QP certify an IMP in the UK, if such an IMP has already been certified in one of the countries on the approved country list. For trials running in the EU, the EU’s current position (as set out in the European Commission’s notice to stakeholders) is that QP certification of an IMP must be undertaken within the EU/EEA.
A manufacturer’s licence (MIA) will be required for all imports of IMPs into the UK. In addition, the IMP supply chain from EEA states will allow direct supply to clinical investigator sites. For IMPs coming from countries on the approved country list, the MIA(IMP) holder will be required to put in place an assurance system to check those IMPs have been QP certified in the EU or EEA. A QP must oversee this system, but the IMPs would not require re-certification. As is the case now, IMPs coming from other countries would require QP certification in the UK by the MIA(IMP) holder.
Sponsors will have 12 months after Brexit to comply and the MHRA will publish guidance that is more detailed before the UK leaves the EU (ie before the 12 months transition begins).
Currently the UK requires sponsors to submit all UK relevant suspected unexpected serious adverse reactions (SUSAR) reports to the MHRA and this will continue via UK based IT systems, since the option to report via EMA systems will no longer exist. Submission to the MHRA of annual safety reports will still be required for all UK trials as they are now.
Since clinical trials are managed nationally, UK clinical trial applications would continue to be authorised by the MHRA and ethics committees as they are presently. The guidance provides that the UK’s ability to participate in multinational trials will also not change. The guidance states that the MHRA will be improving processes for clinical trials to enable closer working with ethics bodies and allow a single application and a single national decision in the UK. The initial pilot work has started and will continue post Brexit.
Publishing trial results
The guidance notes that the UK’s overall intention is to align transparency provisions with those currently operating in the EU, in order to eliminate the need for companies to duplicate efforts. The guidance provides that sponsors should continue to use existing and established international registries such as EudraCT (EU), ISRCTN (International Standard Randomised Controlled Trial Number) registry, ISRCTN (UK), and ClinicalTrials.gov (USA). Patients and clinicians will continue to have access to information about trials being conducted in the UK via the UK Clinical Trials Gateway. As part of the new Clinical Trials Regulation, the EU is introducing a new portal. The guidance notes that by the time the EU’s new portal goes live, the UK will have its own specific hub that would give both UK patients and researchers a single reference point for all UK trials.