The European Medicines Agency (EMA) new location will be Amsterdam, but the buildings (also the temporary ones) seems to be far to be available by March 2019, when the Brexit should finally occur. The decision of the European Council of November 20th, 2017 was taken at draw and left Milan defeated, the favourite city under the technical contents of the candidature dossier.
EMA updated the Q&A
After the decision, ΕΜΑ published an update to the Questions & Answers (EMA/478309/2017) for companies providing practical guidance for the procedures related to Brexit for medicinal products within the framework of the Centralised Procedure (CP).
Pharmaceutical companies are required to update their authorisation dossiers, as well as the investigational ones, in time to be ready from the regulatory point of view to meet the new requirements that shall come into force from 30 March 2019. It is not yet known how UK will position within the trade market after that date, thus the scenario considered in the guideline is referred to an hypothetical “third country”.
According to the document, companies can group different Brexit-related variations provided that the grouping does not delay implementation of changes which need to be in place by the time of UK’s withdrawal. EMA advices to check relevant details with the Procedure Manager (for products intended for human use) or the write to the e-mail address firstname.lastname@example.org for the veterinary ones.
Each batch of finished product must be certified by a Qualified Person (QP) within the European Economic Area (EEA) before being released for placing on the market in the EEA or for export. Also the site for batch control needs to be located in the EEA or a country covered by a Mutual Recognition Agreement (MRA). Variations have to be filed to meet these requirements for products manufactured and/or released in UK.
The guideline also provides a table to classify Brexit-related changes impacting on the manufacturing activities. Introduction of a new manufacturing site for the active substance or for the finished product and their respective consequential changes can be submitted as a Type II variation separately for the active substance and for the finished product, thereby replacing a large grouping of Quality IB (and IA) variations for the consequential changes.
A Marketing Authorisation Holder (MAH) currently established in the UK will need to be replaced with an MAH established in one of the remaining countries of the EEA. In this respect a proof of establishment for the new MAH within the EEA, issued in accordance with national provisions will need to be provided as one of the supporting documents for the transfer application. Timelines for the transfer are to be agreed during the transfer procedure, but in any case the procedure must be fully completed and implemented by MAH before 30 March 2019. In case the transfer procedure concerns a medicinal product whose name is constructed as [international non-proprietary name (INN) / common name + name of the MAH], it may need changes to reflect the name of the Transferee.
Regulatory procedures can run in parallel with the Brexit-related marketing authorisation transfer application, provided the due consideration to avoid that the decision making processes of the procedures will overlap. An application for transfer of orphan designation has to be submitted at the latest in parallel with the application for transfer of the Marketing Authorisation (MA) since the opinion on the orphan designation transfer has to be reached before the opinion on the MA transfer. Sponsors currently established in the UK will need to be replaced with a new sponsor established in one of the remaining EEA countries, at the latest by the date on which the UK leaves the Union.
To facilitate handling of a large volume of transfer applications, a combined version of each required supportive document (except product information and, when applicable, mock-ups) can be created covering all products affected. The combined supportive documents should be submitted with each related transfer application and a declaration should be included in the cover letter, listing the related parallel transfer applications and confirming that supportive documents are identical.
The Qualified Person for Pharmacovigilance (QPPV) must reside and carry out his/her tasks in an EEA member State, as well as the Pharmacovigilance Master File (PSMF) location. Upon a change in the QPPV or location of the PMSF, the Article 57 database should be updated by the MAH immediately to allow continuous supervision by the Competent Authorities. There is no fee to be paid for updates in Article 57 database.
The point of view of the industry associations
A “no deal” scenario will deeply affect the supply of medicines for patients in the EU, according to a survey by the European Federation of Pharmaceutical Industries and Associations (EFPIA).
About 70% of EU investigational products are released from the UK, and there are 1,500 ongoing EU clinical trials with UK as sponsor (50% of those expected to be still active in March 2019). There are approx. 1,300 authorised EU products tested and released from Britain. The MAHs of centrally authorised products based in UK are approx. 400, and 45 millions of patients packs are supplied every month from the UK to EU countries. According to the report, 45% of EFPIA members expect trade delays in the supply of medicines if Britain will move to WTO rules. The 60% of the members of the Association also have a batch release based in the UK.
The associations representing the European and British life science industry (AESGP, ABPI, BIA, BGMA, EBE, EFPIA, EUCOPE, EuropaBio, Medicines for Europe, PAGB, Vaccines Europe) also published a joint policy document on the potential impact of the Brexit.
Medicines should be a priority in phase 2 of the Article 50 negotiations between Britain and the European Union, they jointly ask, and focusing on the framework for transitional arrangements and future relations with the UK must also be considered as it will be critical in ensuring a minimal disruption to patients receiving medicines after the Brexit will occur. With this regard, the warning is to keep in mind during negotiations the integrated nature of the supply chains for medicines across Europe. Among other key priorities are the close cooperation in ensuring that patients in the EU and the UK can continue to access medicines, a trade scheme appropriate to the movement of medicines between both regions, the possibility for UK to remain in the single market or in a new legal arrangement with the EU based on consistency of regulatory frameworks and aligned IP systems in order to avoid uncertainties for industry.