By Evelyn Schulz & Susann Jahn | Noerr
Following our article “Brexit with or without a deal: Consequences for pharmaceutical companies”, which provided a general overview of the challenges facing pharmaceutical companies, this article deals specifically with the impact of Brexit on medicinal product marketing authorisations.
Whether there will be a Brexit with or without a deal is of secondary importance with regard to medicinal product marketing authorisations – this question primarily determines the period within which pharmaceutical companies will be confronted with the new legal situation (see Outlook below in section 3.). Only a very unlikely “exit from Brexit”, i.e. the cancellation of the withdrawal, could avert the consequences outlined below. As things stand at present, however, no company should even speculate about this.
Having said that, the impact of Brexit on marketing authorisations differs according to the type of marketing authorisation. Purely national marketing authorisations will continue to apply for their respective country of validity both before and after Brexit. On the other hand, central marketing authorisations and national authorisations granted under European procedures for several Member States (MRP/DCP marketing authorisations) will be affected by Brexit.
Central marketing authorisations
Central marketing authorisations are those that have been granted on the basis of Regulation (EC) No. 726/2004 for the territory of all Member States of the European Economic Area (EU Member States, Iceland, Liechtenstein and Norway).
The issuing authority is the European Medicines Agency (EMA), which has already relocated its headquarters from London to Amsterdam due to Brexit (Regulation (EU) No. 2018/1718). The assessment reports on which the marketing authorisation decision is based are not, however, submitted by the EMA itself, but by the competent authorities of two Member States, which as rapporteur and co-rapporteur are in overall charge of the marketing authorisation application concerned.
Once the United Kingdom has left the scope of central marketing authorisations, it can no longer assume the (co-)rapporteur function for central marketing authorisations. For existing marketing authorisations and ongoing marketing authorisation procedures, the UK portfolio has therefore already been redistributed to the national marketing authorisation authorities of the EU 27 on the basis of a procedure drafted by the Preparedness Working Group of the European Medicines Agency. Germany, and specifically the Federal Institute for Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (PEI), have received a large number of the (co-)rapporteurships in the field of human pharmaceuticals which are supervised by the United Kingdom (cf. the Federal Government’s answer to the Minor Question from Members of the FDP Parliamentary Group, BT-Drucks 19/5161). The distribution of the UK (co-)rapporteurships takes place centrally via the European Medicines Agency. It is not necessary to arrange for the marketing authorisation holders concerned to arrange for this to be done separately.
However, holders of central marketing authorisations for the distribution of their medicinal products in the United Kingdom will have to submit new applications for UK national marketing authorisations. Since the United Kingdom will no longer be within the territory of the European Economic Area after Brexit, central marketing authorisations in the United Kingdom will lose their validity. It is therefore advisable to apply for such a national marketing authorisation now in preparation for Brexit. The application for a purely national marketing authorisation is basically inadmissible in addition to a central marketing authorisation. However, the UK marketing authorisation can, however, be applied for at the time when the central marketing authorisation for the United Kingdom loses its validity. On UK territory, the purely national marketing authorisation would therefore not exist in addition to the central marketing authorisation.
If pharmaceutical companies headquartered in the United Kingdom wish to continue to market medicinal products within the European Economic Area under a central marketing authorisation, they must relocate their headquarters to the European Economic Area or seek a European representative to market the medicinal product for them in the EEA. Also, the obligations associated with distribution, such as pharmacovigilance and clearance declarations, can only be assumed within the European Economic Area by a person with responsibility based in the EU.
As a result, the establishment of dual distribution structures is necessary for the distribution of medicinal products both in the European Economic Area and in the United Kingdom.
For further information, we recommend the guidance on centrally authorised products published by the European Medicines Agency.
MRP/DCP marketing authorisations
MRP/DCP marketing authorisations are both national marketing authorisations that can be obtained within the European Union for several – but not necessarily all – EU Member States.
They differ as follows: In the Mutual Recognition Procedure (MRP), a marketing authorisation granted by one Member State is recognised by the other Member States involved. In the Decentralised Procedure (DCP), the application for the national marketing authorisations is submitted simultaneously in a uniform procedure. What both procedures have in common is that each Member State, as the Reference Member State (RMS), prepares an assessment report which forms the basis for the decision to grant marketing authorisation in the participating Member States (Concerned Member State, CMS).
Once the United Kingdom has left the scope of MRP/DCP marketing authorisations, it will no longer be able to act as a Reference Member State for these MRP/DCP marketing authorisations. It is therefore necessary to change the function of the Reference Member State for existing authorisation procedures in which the United Kingdom is a Reference Member State. The change requires the application of the marketing authorisation holder; an automatic change does not take place. The Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has included the withdrawal of a Member State from the European Union in accordance with Article 50 of the Treaty on European Union as a possible reason for the change in the template for the change application and has thus expressly recognised it as a legitimate reason for the change.
Brexit has no direct effect on the existence of MRP/DCP marketing authorisations, as these authorisations are ultimately only national authorisations despite the Community application procedure. They therefore remain valid in the country in which they apply. If, on the other hand, changes to the marketing authorisations are required after Brexit and the United Kingdom continues to be responsible for the marketing authorisation as a Reference Member State, the change of the Reference Member State as described above would be necessary for a variation. It is therefore also recommended for existing marketing approvals that the change from the United Kingdom as the Reference Member State be arranged now.
For further information we recommend the document “Practical guidance for procedures related to Brexit for medicinal products for human use approved via MRP/DCP” published by the Coordination Group on Mutual Recognition and Decentralised Procedures.
In January 2019, the UK Parliament will vote on the “exit deal” negotiated by Theresa May with the European Union. This withdrawal agreement would ensure that the UK’s withdrawal would not take full effect until 1 January 2021. Pharmaceutical companies would therefore have until the end of 2020 to implement the above measures. Secondly, Article 44 of the Withdrawal Agreement provides for a provision for ongoing marketing authorisation procedures whereby UK authorities would make all relevant documents available to those authorities which have assumed responsibility for the relevant marketing authorisation procedure after Brexit. This would at least save companies from having to re-submit previously submitted marketing authorisation documents to the now competent EU 27 authority in ongoing procedures.
Finally, there is still the possibility that the United Kingdom will revoke its declaration of withdrawal. The admissibility of such a unilateral “withdrawal from the agreement” has meanwhile been confirmed by the European Court of Justice in its decision of 10 December 2018 (ECJ, 10 December 2018 – C-621/18, Wightman et al.). However, the probability that the UK government will reverse Brexit is still extremely low. It is therefore advisable for the pharmaceutical companies concerned to initiate the measures described above as a precautionary measure at an early stage.
Compliments of Noerr, a member of the EACCNY