In the run up to the 31 October deadline, the Government published further guidance on the regulation of medicines, medical devices and clinical trials of investigational medicinal products (“IMPs”) in the event of a No Deal Brexit. Given the UK’s status as a leading R&D centre in the pharmaceutical industry, not surprisingly the Government is seeking to limit the quantity and impact of any changes.
At the time of writing, the likely outcome in relation to Brexit is a Withdrawal Agreement will be reached. However, businesses involved in the conduct and management of clinical trials may want to take note of the possible implications of a No Deal Brexit on their operations and the actions they should be taking, as it does not appear that the Government will update its advice in the near future.
What does the guidance say about clinical trials?
In a No Deal Brexit, the UK will no longer participate in the EU regulatory system for clinical trials and, as such, the MHRA will undertake a number of the responsibilities that previously rested with the EMA. The guidance outlines how this new framework will affect the regulation of clinical trials, which we briefly summarise as follows: (1) recognition of the status quo, (2) proposed alignments with the current legal framework and (3) substantive changes to future clinical trials in a No Deal Brexit.
Recognition of the status quo
The UK will continue to:
- recognise regulatory and/or ethics approvals already given to a clinical trial,
- require annual safety reports, details of the lead principal investigator in any UK trial and clinical trial applications to be reported to/authorised by the MHRA,
- be able to participate in multinational trials,
- recognise Qualified Practitioner certification for those IMPs that are coming into the UK, where certification has been conducted in an “approved country”. The guidance indicates that this would initially include all EU/EEA countries, circumventing the need for dual certification in an EU/EEA state and the UK.
It is not clear how long a time period “initially” covers but it foreshadows a scenario in which a Qualified Practitioner certification will need to take place in the UK as well as the EU/EEA. Sponsors should consider how to reflect any additional time/cost in respect of undergoing dual Qualified Practitioner certification of IMP products in their clinical trial agreements, whilst keeping up-to-date with developments in this space.
- As the EU Clinical Trials Regulation 536/2014 is not yet in force, it will not take effect in the UK if exit day precedes its implementation. However, the Government has announced its intention to, where possible, align these regulations within the current UK framework.
- Whilst this suggests that the Government wishes to harmonise EU and UK legislation post-exit day, the extent to which it will do so remains unclear.
- Serious adverse reactions in UK trials will now need to be reported to the MHRA as access to EU reporting systems will cease.
- Those responsible will now need to submit reports via a UK based IT system.
- At least initially, trial results should continue to be published on existing, established international registries, seemingly until the UK’s new centralised portal goes live. In the longer term, the guidance suggests that the UK intends to align its transparency requirements for the publication of trial data with EU requirements to minimise duplication.
The UK Government has not provided any further guidance, especially as to how and when it will align UK publication requirements, but the intention appears to be to move away from an international regime to a UK focused one. Unless and until notified further by the Government, sponsors should continue to publish their trial results in the same way.
Changes to be aware of
- The Government requires the sponsor or its legal representative to be located in either the UK or an “approved country” (again, to include initially the EEA/EU). However, where a trial is being conducted throughout the EU, a point of contact (e.g. a local sponsor/representative) must be based in the EU.
- Although EU-based sponsors/legal representatives are, for now, still permissible points of contact, it is not clear how long this will remain the case. Regardless, pan-EU trials which currently have a UK sponsor or legal representative, will need to establish an EU-based legal representative. Sponsors and CROs should consider whether they already have an EU point of contact that they could use and how this requirement may affect liability and indemnity provisions within clinical trial agreements.
- Those importing IMPs into the UK from an "approved country" (initially, the EU/EEA) will need a UK Manufacturing and Import Authorisation UK (MIA(IMP)). UK (MIA(IMP)) holders will establish an assurance scheme to check IMPs being imported into the UK have been QP certified in an “approved country”. IMPs will not, however, require recertification. Sponsors have 12 months from exit day to comply.
If sponsors are UK (MIA(IMP)) holders, they can conduct these checks themselves but otherwise they will need to outsource this verification. This may drive up cost and timings as the relationship between the Sponsor and UK (MIA(IMP)) holder will need to be negotiated and documented.
Whilst this guidance is a means to assess the Government’s current state of mind, it is not in any way a definitive statement of intent. Businesses in this space should prepare on the basis of the guidance but also be aware that more significant changes could come further down the line.