Consequences of Brexit for future and ongoing clinical trials

Should there be no specific agreements regarding medicinal products between the European Union (EU) and the United Kingdom (UK), the following issues concerning clinical trials with medicinal products must be observed after
the United Kingdom has withdrawn from the EU on 29 March 2019 (Brexit):

Establishment requirements for sponsor or legal representative

The sponsor of a clinical trial or his legal representative must be located in a Member State of the European Union or in another State party to the Agreement on the European Economic Area (EEA). If this is not the case, the prerequisites both for authorisation and for conducting of clinical trials pursuant to Section 40 sub-section 1 sentence 3 number 1 of the German Medicinal Products Act (Arzneimittelgesetz, AMG) no longer apply.

In the case of clinical trials where the sponsor or the legal representative are still established in the UK, their registered office must be transferred to the EU/EEA or a legal representative in the EU/EEA must be designated by the time Brexit becomes effective, otherwise, one of the basic prerequisites for conducting a clinical trial will cease to apply.

Manufacture and batch release of investigational medicinal products

The batch release of investigational medicinal products must take place in the EU/EEA. After Brexit, manufacturers responsible for final batch release who are established in the UK can no longer be accepted and must be replaced by manufacturers established in the EU/EEA. Batches that were released prior to Brexit can be used without having to renew batch release. However, after Brexit, an extension of the shelf-life of an already released batch requires release by a qualified person (QP) established in the EU/EEA. It should be observed, that changing the manufacturer responsible for final batch release constitutes a substantial amendment.

Shipping of investigational medicinal products/medicinal products from the UK will now constitute an import

After Brexit, the shipping of investigational medicinal products and other medicinal products from the UK to the EU/EEA will constitute an import. If manufacturing steps of the investigational medicinal products are performed in UK and these are subsequently shipped to the EU/EEA, they will then require a corresponding import authorisation. This also applies if only parts of the manufacture take place in the UK, e.g. study-specific packaging or labelling of investigational medicinal products.

For this procedure, an importer established in the EU/EEA is to be designated. In Germany, this importer must have an import authorisation pursuant to Section 72 AMG. Importers established in other states of the EU/EEA require a corresponding import authorisation based on their national legislation (in agreement with the requirements laid down in Article 13 of Directive 2001/20/EC).

Furthermore, the importer's QP must certify that the manufacturing standards of the manufacturer established in the United Kingdom conform with EU GMP standards.

Obligation to notify amendments regarding sponsor, sponsor's legal representative, manufacturers responsible for final batch release and importers

Subsequent amendments regarding sponsor, the sponsor's legal representative as well as manufacturers (responsible for final batch release) and importers of investigational medicinal products are considered substantial and as subsequent amendments pursuant to Section 10 sub-section 1 of the German Ordinance on the Implementation of Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Use in Humans (GCP-Verordnung, GCP-V) must be authorised by the competent federal higher authority prior to their implementation. Should amendments also affect the competence of ethics committees, they require a positive assessment by the competent ethics committee prior to implementation. In this connection, the 20/35-day deadlines should be taken into consideration. In order to avoid long processing times we urgently recommend early submission of the notifications of amendment.

Please click on the following link in order to access the corresponding notice from the European Commission:

https://ec.europa.eu/info/sites/info/files/notice_to_stakeholders_brexit_clinical_trials_final.pdf