Well, the politics of the European Union and the UK are unfortunately making life more complicated for everyone. The folks in the pharmaceutical world, including we pharmacovigilantes, are being touched.
Here’s the Latest
In March of this year the UK officially notified the EU that they will withdraw from the EU. A member state has two years to do so. Thus the UK is supposed to be out of the EU (and the EMA) by March 30, 2019. Negotiations are due to start soon. As there is no precedent for this, it is totally unclear how this will unroll. Whether the complex negotiations will be done within this time frame is controversial.
The recent UK elections which resulted in the Conservative Party government losing its majority in Parliament and forming a less stable coalition government, has thrown the issues involved in Brexit up in the air. The UK’s negotiating position is now less clear. Nonetheless, the UK and the EU are saying negotiations will begin shortly and must be completed by the end of March 2019. Whether this will occur, whether the deadline is extended, whether Brexit somehow gets reversed – all of this is up in the air.
Working on the proposition that the UK really will be out of the EU by 2019, the various parts of the EU bureaucracy have started thinking through the issues and are beginning to make plans for the post-Brexit EU. It is likely that those issues which can more easily be resolved sooner rather than later will occur. Thus, it is likely the EMA move will continue.
The View from the EU
The European Commission and the EMA issued a bulletin a short while ago. Among the pertinent comments:
“…marketing authorisation holders of centrally authorised medicinal products for human and veterinary use are reminded of certain legal repercussions, which need to be considered:
- EU law requires that marketing authorisation holders are established in the EU (or EEA);
- Some activities must be performed in the EU (or EEA), related for example to pharmacovigilance, batch release etc.
- Preparing for the consequences of the UK’s withdrawal from the Union is not just a matter for European and national administrations, but also for private parties.”
Significant changes will need to be made by governments as well as private companies, CROs, vendors etc. This will be rather complex. Some changes will require “variations” in the EU. Some won’t.
The EMA has also set up a webpage covering Brexit and this should be referred to frequently. On this page is a four page Q&A. Here are some of the key questions and answers:
There are two questions on pharmacovigilance in this document:
4) What if my Qualified Person for Pharmacovigilance (QPPV) resides and carries out his/her tasks in the UK?
The QPPV must reside and carry out his/her tasks in the Member State of the Union (EEA). The QPPV will therefore need to change his/her place of residence and carry out his/her tasks in the Union (EEA) or a new QPPV residing and carrying out his/her tasks in the Union (EEA) will need to be appointed.
5) What if my Pharmacovigilance System Master File is located in the UK (PSMF)?
The PSMF must be located within the Union (EEA). The supervisory authority for pharmacovigilance is the competent authority of the Member State in which the pharmacovigilance system master file is located .The marketing authorisation holder will therefore need to change the location of the PSMF to a Member State within the Union (EEA).
Other questions and answers of interest less directly related to PV are also noted:
1) What if I am a marketing authorisation holder established in the UK ?
The marketing authorisation holder (MAH) must be established in the European Union. Through the EEA Agreement this is extended to include also Norway, Iceland and Liechtenstein. For centrally authorised medicinal products the MAH will therefore normally need to transfer its marketing authorisation to a holder established in the EU (EEA).
6) What if my manufacturing site of the active substance is located in the UK?
Active substances manufactured in the UK will be considered imported active substances. MAHs are obliged to use, as starting materials, only active substances that have been manufactured in accordance with the detailed guidelines on GMP for starting materials. Active substances shall only be imported in the Union (EEA) if the active substances are accompanied by a written confirmation from the competent authority of the exporting third country confirms that the standards of good manufacturing practice and control of the plant are equivalent to those in the Union (EEA).
7) What if my manufacturing site of the finished product is located in the UK?
Medicinal products manufactured in the UK will be considered imported medicinal products. The competent authorities of the Union (EEA) shall ensure that the import of medicinal products into their territory is subject to an authorisation in accordance with the EU directives on importation (See the Q&A article for full detail).
For centrally authorised medicinal products the marketing authorisation holder will therefore need to specify an authorised importer established in the Union (EEA) and submit the corresponding variation. There is another question covering batch release. See the document.
In regard to the EMA, there is little else on the EU or EMA’s websites beyond:
“The location of the Agency after Brexit will depend on the future relationship between the UK and the EU, which is unknown at present. Representatives of the Member States will determine the Agency’s location by common agreement.”
There are, however, various news reports on what is happening behind the scenes. There appears to be a lively discussion about where the agency will end up. According to a Reuters article in April, many countries are interested in hosting the EMA: Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Malta, Netherlands, Portugal, Romania, Slovakia, Slovenia and Spain. The EMA is one of the largest institutions in the EU bureaucracy with about 900 workers. Meetings have been held in the EMA and another high level meetings is expected to be held in July to further discuss Brexit.
Several Japanese industry associations have been more blunt about the problems that Brexit is causing pharma firms in Japan.
A very interesting report prepared by the consultancy KPMG compares the various possible European cities’ desirability for the EMA. See their long presentation here. Briefly, they looked at the following parameters: “Dynamic and size of the life science clusters, Research and scientific environment, connectivity and infrastructure, size of the national competent authorities, political stability, absence of violence, terrorism and corruption, Quality of Life including attractiveness for families and spouses, housing. Their conclusions were that the top tier of cities felt to me most capable of having the EMA are: Paris, Copenhagen, Stockholm, Munich, Amsterdam and Berlin. Next level down includes: Vienna, Lyon, Bonn, Dublin, Brussels and Barcelona. The least attractive would be Madrid, Milan, Lisbon and Rome.
Some reports indicate that a decision might be made by October of this year.
Everything, however, is up in the air right now.
The View from the UK
From the UK point of view, some functions that were handled in other EU member states will need to be done in the UK in addition to the EU. Some/many internal functions ongoing now in the MHRA will also change. There is nothing of note on the MHRA’s website covering this. Doubtless, there will be much more forthcoming soon.
As of now, Brexit is moving ahead though details are sparse. It does look like the EMA is going to leave London within the next two years. Discussions are underway and there is some indication that a decision on the new venue will be made in October though this is by no means certain.
What to do now?
- Pay attention to the news and what is happening. Check periodically on the EMA and MHRA websites.
- Begin discussions on how PV and regulatory changes will be handled in your organization. Expect that changes will be necessary and that addition work and requirements will come into being. Submissions that went to one site in the EU may now need to go to the UK in addition perhaps in a different format.
- Consider avoiding the UK as a rapporteur or the point of contact for EU dealings. It is unlikely that an institution can yet change the rapporteur or contact based solely on the Brexit issue but if there is a choice for future products, consider one of the other EU member states.
Tags: brexit, drug safety, ema, EU, Pharmacovigilance