Dec 7, 2020

The departure of the United Kingdom from the European Union on January 1, 2021, has many consequences. Clinical investigations with medical devices as well as clinical performance studies with in vitro diagnostic devices are impacted, as are clinical studies with medicinal products. In this respect, Brexit means that sponsors and study subjects (patients) may find themselves on different sides of a new EU outer border. Where the single market relies on one set of rules, different rules will apply for different markets –  newly defined in the EU and UK as of January 1, 2020.

Studies performed in the EU with UK-based sponsors

The EU has a clear set of rules to protect its citizens in case of clinical studies on or with humans. Those rules cover studies done by EU-based sponsors as well as non-EU sponsors, with one difference: The non-EU sponsor must appoint an EU-based Authorized Representative (in case of a study falling under the current Medical Device Directives) or legal representative (in case of a study falling under the new Medical Devices Regulation (MDR) or In-vitro Diagnostic Medical Devices Regulation (IVDR)). This EU representative will be responsible for the sponsor’s obligations. Studies started under the current EU Directives can keep relying on an Authorized Representative and do not need to switch to a legal representative on the MDR’s date of application on May 26, 2021. There are differences between the Authorized Representative and the legal representative; the Authorized Representative is mainly responsible for notifications, whereas the legal representative, to our understanding, manages the sponsor’s compliance.

Reporting of serious adverse events must be submitted to Competent Authorities in every Member State where a clinical study is taking place. The clinical investigation report and its summary must be made public via the Eudamed database, and can be done by the sponsor as well as their representative. In the end it is the representative who will be held responsible for the publication of the report.

Studies performed in the UK with EU-based sponsors

The current Directives will become UK law starting January 1, 2021. This means that for ongoing studies only some formal requirements will change. MHRA has recently published guidance on clinical investigations with medical devices. This guidance refers to two other documents, one from January 2020, the other without a date.

The January 2020 document provides guidance regarding clinical investigations with medical devices. This document contains reference to the Authorized Representative, similar to the requirements in the current Directives. The Authorized Representative is a concept that will no longer exist in the UK after January 1, 2021, but it is not clear if those tasks will be taken over by the UK Responsible Person (UKRP).

The other document is about compiling a submission to MHRA. It only mentions the manufacturer and does not refer to either the Authorized Representative or the UKRP. Verbally, MHRA signaled to Emergo by UL that there are currently no plans to require a UK-based representative for a non-UK-based sponsor. Still, Emergo recommends that sponsors investigate who could take up the role of legal representative in the UK on relatively short notice. Studies in Northern Ireland will be following the EU rules; therefore the MDR, with its requirement to appoint a legal representative, will apply from May 26, 2021 in Northern Ireland.

Incident reporting of serious adverse events involving UK citizens should be provided to MHRA. The study reports should also be forwarded to MHRA.

Multinational studies

In case of studies done in multiple Member States of which at least one is the UK, the location of the sponsor remains crucial for determining which regime applies.

Studies performed in the EU with UK-based sponsors: act now

Informal contact with the German Competent Authority BfArM indicated that UK-based sponsors must ensure they appoint an EU representative as soon as possible. They may otherwise run the risk that the study could be halted or terminated in Germany starting January 1, 2021, if there is no established mutual agreement in place between the EU and UK; such an agreement is very unlikely in the remaining days of 2020. It is likely that other Member States follow the same approach as Germany and automatically declare these studies as not valid (e.g., based on conflicts with national laws).

Informal contacts with several Competent Authority representatives made clear to Emergo that they have to follow the rules and country regulations, which would automatically bring these studies into non-compliance, which in turn could result in their full stop. However, some Competent Authorities appear to be prepared to accept a reasonable delay in the paperwork supplied by the manufacturer if the procedures to appoint a representative have started already.

Key point: UK sponsors must appoint an Authorized Representative or EU legal representative.

Additional EU and UK medical device and clinical study regulatory resources:

 

Author

  • Ronald Boumans

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