Since 1 February 2020, the UK has withdrawn from the EU and become a 'third country'. Until the end of the transition period (31 December 2020), EU law still applies in the UK. After the end of the transition period, however, EU rules on clinical trials will no longer, by default, apply to the UK. As such, the effect of Brexit on the life sciences industry will be significant, not least for the changes that will occur to the conduct of clinical trials both in the EU and UK.
Depending on the outcome of the ongoing EU-UK negotiations, it is possible that specific or equivalent provisions of the Clinical Trials Regulation (Regulation) will be implemented into UK law, at the appropriate time. The Regulation was adopted on 16 June 2014 but it does not yet apply in Member States due to the need for confirmation of the full functionality of the Clinical Trials Information System through an independent audit. The Regulation will become applicable six months after the European Commission publishes notice of this confirmation, with current estimates that this will not be until 2021, in which case it will not apply in the UK. However, the UK Government has previously indicated that it will seek to align with the Regulation as much as possible.
There is no denying that all players in the life sciences industry are united in so far as wanting continuity of access to medicines and medical devices across the EU and UK and, with this, in the conduct of clinical trials also. As such, in an ideal world, the UK approach to clinical trials would be harmonised with the EU.
Following the EU Commission Notice (EU Guidance), and with no guidance in the Withdrawal Agreement, the Medicines and Healthcare products Regulatory Agency (MHRA) has published two guidance notes on the registration of clinical trials and substantial amendments to clinical trials applicable from 1 January 2021 (UK Guidance).
The UK Guidance provides drug developers with the first indication (at least in the short term and at a high-level) as to the national framework and procedures that the UK will adopt and apply from 1 January 2021 for clinical trials:
- Applications:
- Existing international registries should still be used to publicise trials. Where trials are carried out at both UK and EU sites the EU Clinical Trials Register will detail the trial. The registration of the trial should take place prior to recruiting the first participant but must be no later than 6 weeks after such recruitment.
- Additional EU Guidance on the long-term reporting requirements has been identified as an area of further discussion. UK companies may not have access to the single portal for applications for clinical trials or, if they do, there may be a significant cost, and separate centralised and national clinical trial authorisation procedures may need to be followed.
- Amendments to Investigational medicinal products (IMP):
- Any changes to IMP manufacturing, importation or certificate sites for an ongoing UK trial will continue to require a substantial amendment to the MHRA. However, this does not apply if a sponsor retains the UK site but adds an additional site in the EU/EEA for trials in relation to the EU/EEA.
- The UK Guidance confirms that the IMP supply chain will allow direct supply to clinical investigator sites from a country on the approved country list (such list to "initially" include EU/EEA countries; for how long is not clarified).
- Until 1 January 2022, IMPs may be directly supplied from the EU/EEA holder to the UK (excluding Northern Ireland) ongoing trial site without additional UK oversight if a substantial amendment is submitted to the MHRA providing details of the relevant EU/EEA holder performing that function for importation to an ongoing trial.
- Sponsor/legal representative:
- The UK Guidance makes clear that any sponsor or legal representative of a clinical trial must be based in the UK or in a country on an approved list - which "initially" includes the EU/EEA countries; how long this will remain the position is unclear, as is whether any non-EU/EEA countries are on such approved list.
- This is, at least in the short term, broader than the position under EU law, where the EU Guidance states that the sponsor/legal representative of a clinical trial must be established in the EU/EEA. Accordingly, after the end of the transition period, a sponsor conducting a clinical trial under EU legislation will no longer be allowed to be based in the UK but under UK legislation will be allowed (initially) to be based in the UK or EU/EEA.
- There are extra complications due to the obligation of having to notify the competent authority of the Ethics Committee of a change.
- Submission of Clinical Trial Information:
- In the UK a summary of the trial results for (i) paediatric clinical trials must be published within 6 months of the end of the trial, and (ii) non-paediatric clinical trials must be published within 1 year of the end of the trial.
- The process to submit trial results will change, as the results need to be published on the same public register upon which the trial was registered, and a final report must be submitted to the HRA within the same timeframes set out above. Whilst no report needs to be submitted to the MHRA, companies must send the MHRA a confirmatory email once the results have been submitted to the public register.
- The EU Guidance makes clear that under EU law, the submission of certain clinical trial information to the EU clinical trials database must be made through EudraCT.
Where a clinical trial involves access to and use of drugs, continuity of that access (including for comparator drugs) and supply chain considerations must be considered upfront. This includes, in particular, consideration of distribution warehouse locations, increased inventory and production delays, and continuity of supply of lab kits, samples etc. Potential delays in the supply chain could have severe and drastic consequences for patients, especially where a clinical trial is already underway.
The UK Government has also published the draft Human Medicines (Amendment etc.) (EU Exit) Regulations 2020, along with a draft explanatory memorandum, which will give legal effect to the UK Guidance, as well as amending four Regulations (originally prepared in anticipation of a "No Deal" Brexit) to align and comply with the European Union (Withdrawal) Act 2018 and Northern Ireland Protocol. The changes implement the Northern Ireland's regulatory position as distinct to the rest of the UK and make updates to Great Britain's regulatory regime.
Although the UK may publish further details with regard to clinical trials from 1 January 2021 and beyond, the European Commission, European Medical Authority and Heads of Medicines Agencies have issued a technical notice about clinical trials giving advice on the location of the Qualified Person and location of the sponsor or legal representative.