Clinical Trials – Brexit guidance for sponsors that have a UK presence

For sponsors running clinical trials with any UK presence, it is important to start considering preparations for Brexit now. Substantial changes may be needed which can have timeframes built into the Brexit process. If making these changes is left too late then the trial may face legal compliance risks.

Two potential scenarios can raise issues:
A) Where clinical trials are conducted within the UK, some of the rules are changing; and,
B) When an international organisation uses the UK as a base of operations for EU compliance, they may need to move that base to another EU country.

For both potential scenarios, the European Commission has Brexit preparedness guidelines, including guidance on ‘Clinical trials’.

Sponsors should ask their lawyers to assist them in applying the European Commission’s guidance, specifically paragraph 1 and 3 of that guidance for clinical trials that are conducted within the UK. The European Commission’s guidance is specific, detailed, practical and deals with both scenarios.

The UK Government has also issued guidance on Brexit preparations and clinical trials which is less helpfully written than the European Commission’s guidance and which only really addresses scenario A, i.e. where clinical trials are conducted within the UK. If this guidance is read in isolation, then those facing scenario B (who use the UK as a base of operations for compliance with the EU requirements) will miss an important Brexit preparedness step.

What is that important Brexit preparedness step?

If a clinical trial sponsor has their own UK entity (e.g. a UK limited company) as an establishment in the EU, or if they have a legal representative appointed (perhaps a CRO who is based in the UK who has agreed to act as legal representative) then Brexit will mean that they breach Art 19 of the Clinical Trials Directive, if no action is taken.

This is helpfully set out in paragraph 2 of the European Commission’s guidance which states:

“Establishment Requirements for the Sponsor or the Legal Representative
According to Article 19 of [the Clinical Trials Directive], the sponsor of a clinical trial or a legal representative must be established in the EU. As of the withdrawal date, a sponsor established in the United Kingdom and conducting a clinical trial in [any of the remaining EU member states] has to ensure that a sponsor or a legal representative is established in [any of the remaining EU member states]. The change of the sponsor or of the sponsor’s legal representative is typically a substantial amendment, … which requires notification to the competent authority/information of the Ethics Committee”

To remain compliant post-Brexit, a sponsor needs to make a structural change to the corporate framework pre-Brexit. This would be classed as a ‘substantial’ change under the Directive which has a timescale built into the process for sign-off by an Ethics Committee and competent authority. A ‘substantial change’ engages a procedure set out in Article 10 of the Clinical Trials Directive.

The European Commission’s guidance has a useful footnote (footnote 6) which points to detailed guidance on the request procedures to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of the trial.

The guidance makes clear that an ethics committee may take up to 35 calendar days to reply where their approval is needed – which means that it is important for sponsors, with their lawyers, to start assessing the possible need now.

The Irish regulator has published useful guidance on establishment which states (p10 onwards):

“UK based sponsor or legal representative listed on clinical trial application
Under the current clinical trial directive, Article 19 of [the Clinical Trials Directive requires that the sponsor or a legal representative of the sponsor is established in the [European Union or European Economic Area]. This does not exclude the possibility that this establishment is a branch or subsidiary of a legal person having its principal seat outside the EU. This establishment could be the sponsor or act as legal representative of the sponsor established outside the EU. ”