There have been several events occurring in the EU/Europe that will play on pharmacovigilance. One that we’ll address here is the vote by the United Kingdom (UK) to leave the European Union (EU).
In late June 2016, the UK voted to leave the EU. A new government has been installed with the Prime Minister and government accepting and implementing the vote to leave. It is likely the process will take at least two years and possibly longer. It is unclear how the divorce will play out. Clearly, the UK is part of Europe and will set up new or altered trade, banking, immigration, pharmaceutical and many other processes with the remaining 27 member states of the EU as well as with individual countries – particularly the US, Canada, Australia, New Zealand and India. No one knows how this will all play out.
What the EMA and MHRA are Saying About Brexit and Pharmaceuticals
The EMA has released a statement and the issue was also discussed at the recent June DIA annual meeting. See the various reports including:
“…it is now up to the UK government to decide how to act upon the outcome of the referendum.
EMA would like to underline that its procedures and work streams are not affected by the outcome of the referendum. The Agency will continue its operations as usual, in accordance with the timelines set by its rules and regulations.
No Member State has ever decided to leave the EU, so there is no precedent for this situation. The implications for the seat and operations of EMA depend on the future relationship between the UK and the EU. This is unknown at present and therefore we will not engage in any speculations.”
Some Things Do Seem Likely, In My View:
The European Medicines Agency will leave London. They have been there since creation in 1995 and have a strong presence with nearly 900 employees, many non-British. Several member states have already expressed interest in having the EMA relocate to their shores: Spain, Sweden, Italy, Denmark and Germany. There will be a complex political negotiation/battle over this and it is hard to predict where it will land. One thing that everyone will wish for is a relocation to a city with a good airport and lots of connections. Delegates to the various committees and functions at the EMA must come in monthly (often staying several days or a week or more) for meetings and easy access will be sorely wished for by such commuters and, of course, those of us who have to go there to attend meetings and conferences.
The British personnel working in the agency will likely have to leave as they will not be able to stay unless a special arrangement is made in the future UK/EU relationship. In particular, this will touch the Pharmacovigilance Risk Assessment Committee (PRAC). The current chairperson on PRAC is British as is one of the expert advisors and one of the patient representatives. The British have always played a strong and key role in the EMA and on the PRAC. Some or many of the British employees will start drifting out later in the year or 2017 as it becomes clear that their employment will end. Some will stay on until they are forced to leave. This will produce turbulence, delays, items falling through the cracks etc. Anyone in the industry who has lived through a merger or a company relocation to a new location knows what will happen!
There will be secondary effects on the UK drug agency (MHRA). They will certainly have to pick up some duties currently handled by the EMA and other Member State Health agencies. The MHRA will need to make changes in both high-level processes and duties as well as day-to-day operations. Unless they negotiate some level of continuity and use of EMA directives, regulations, databases, MA approvals, etc. much of this will have to return to the MHRA. Whether there will be sufficient personnel and budget for this remains to be seen. Clearly, there will be turbulence, change and delays.However, there will surely be an arrangement with the EMA perhaps similar to the arrangements that the Swiss agency has with the EMA. Perhaps the UK will still accept mutual recognition (approval) and sharing agreements. Norway, Iceland and Liechtenstein work with the EMA even though they are outside the EMA and EU. Perhaps PV and the PRAC will, somehow, continue jurisdiction in the UK through a mutual agreement. All this remains to be seen.
Interestingly, language issues may arise. English is now the de facto EU language and, with the EMA sitting in London, is clearly the working language of the EMA. After the UK leaves the EU, there will only be two (small) primarily English speaking countries: Eire (Ireland) and Malta. There is already a push for increased use of German and French in the EU in addition to English. The European Commission president, Jean-Claude Juncker, of Luxembourg refused to speak English to the EU Parliament on June 28 as he normally does. Although petty, this is perhaps a sign of change already. Clearly with fewer Brits in the EU and the agencies, there will be less English and less native English (for better or worse…).
Some Things are Less Clear. Here is Some Speculation:
It’s possible that drug reviews and approvals will be delayed, particularly if a separate approval is required for the UK apart from centralized approval for the remaining 27 member states.
Companies with the UK as an EU rapporteur may have to find another rapporteur for processes and approvals underway. It is questionable whether any company should/would want to use the UK as a rapporteur going forward now and it will not be possible after the UK leaves – again unless some special arrangement is put into effect.
Clinical trial PV reporting will be altered in ways that are as yet unclear. SUSARs and periodic reports may have to be reported separately to the UK as well as EudraVigilance.
Post-marketing reporting will also likely be altered. This will include SAEs/SARs, PSURs/PBRERs, compassionate use, etc. Risk Minimisation Plans with commitments and studies (e,g, PASS) outside the UK may or may not need to be altered. The reporting timelines on the Union List for PSURs may or may not change and may or may not be accepted in the UK. The newly installed EMA literature searches and requirements may or may not be useable for the UK.
My view is that there will be good will on the part of the remaining EU Member States and the UK, particularly in the area of pharmacovigilance. No one anywhere wants to put the public health at risk. Surely the FDA, Health Canada and the other agencies will work with the UK MHRA and EMA to ensure that safety information and issues continue to be discussed and data exchanged. It is, however, unlikely that the WHO, Uppsala Monitoring Centre or other international agencies and NGOs will take over these roles or new duties. ICH, CIOMS and other organizations will continue their work.
Money and budgets will be a big issue. “He who pays the piper calls the tune” as the old saying goes. Brexit will now be a political issue, not a medical or scientific issue.
It’s not at all clear the EMA will have a big say in its future. Their new world will probably be largely out of their control.
What to Do Now:
Any company, NGO, health agency etc. really needs to set up a system of regulatory, political and drug safety intelligence to follow what is happening. This includes not only scanning the internet but also keeping in touch with people on the ground in the UK and EU with good sources of information (and gossip).
Companies with on-going or upcoming MA submissions in which the UK is involved directly should also pay close attention and consider developing a Plan B, particularly if the submission is months to a year two down the road. Expect delays, uncertainty, vague “official” information and instructions and last minute changes.
In terms of PV, don’t make any changes yet and continue to do everything you must do under UK and EU/EMA requirements. Keep channels of communication open with vendors, CROs, safety database companies etc. Continue to do signaling, RMPs etc. Start considering a Plan B. If your organization or company has a UK office, set up more detailed lines of communication and be sure the folks there have a real tracking mechanism in place and that they communicate news to the rest of the company. Similarly for offices within the Member States, in particular the large and key Member States (e.g. France, Belgium, Germany, Spain, Netherlands etc.).
Pharmacovigilance is always an area of uncertainty where the next email or phone call can herald a major drug problem or crisis. This merely adds to our exciting workload!
Pharmacovigilance, Drug Safety and Regulatory Affairs Author & Expert
Bart is a pharmacovigilance and drug safety consultant with 30 years in the pharmaceutical industry. He was a founding member and working group chair in ICH, and has written 4 textbooks on drug safety. Bart offers expertise in all areas of strategic pharmacovigilance including data management committees, mock Advisory Committee meetings, FDA & EMA/MHRA/AFSSAPS interactions, compliance, training, risk management (REMS/RMPs), crisis management, medical & safety analyses & white papers, and organizational change management. He is also a board certified gastroenterologist.