Jurji Petrin
Jurji Petrin
Senior Vice President Global Regulatory Affairs

Brexit is currently projected to occur on 30 March 2019. Unless the UK and EU politicians find a solution to cancel or at least postpone it, after that date the United Kingdom will no longer be a member of the European Economic Area (EEA), and several changes will occur in the pharmaceutical arena.

Our Jurij Petrin explores what this means for pharma and patients.

Not only are there many challenges and decisions in the road ahead, but there are many uncertainties, as well, as Brexit is “in progress” and not driven by pharma, but rather driven by politics – which leaves us in a “wait and see” holding pattern. Here are some of the issues at hand:

Marketing Authorization Holders

For many years, the EU has operated as a single market for medicines. According to Regulation (EC) No 726/2004, a marketing authorization holder (MAH) as well as a sponsor of an EU orphan medicinal product designation, must be established in the EEA.

Currently, close to 400 MAHs – with several thousand medicinal products – are registered in the UK. To accommodate the United Kingdom’s exit from EEA, these marketing authorizations will need to be amended by changing the MAH established in the UK to the MAH established in one of the remaining EEA countries. This applies to both centralized and nationally authorized products. Unless legislation changes, if these variations are not completed on time, Brexit may cause major disruption of supply of medicines, with some products possibly not being available for patients at all beyond March 2019.

European Medicines Agency

The European Medicines Agency (EMA) is now in London but will be relocating to Amsterdam by March 2019. The change to a new host city will be a smooth transition, with working practices expected to remain the same. For current, ongoing trials, if the IP release site is within the UK, trials may be impacted, and substantial amendments may be needed; an EU release site would be required. Also, only citizens of the EU can be EMA employees, so UK citizens could be excluded from that opportunity. Further, it’s possible that the EMA move could lead to delays in product approvals as that move occurs, since it could disrupt the fixed product approval timelines.

Clinical Trials

There are some challenges ahead for clinical trials and research. For example, sensitive populations could be left at risk when the UK leaves the EU, such as rare disease patients and children. That’s because the UK could lose access to collaborative trials and research activities that take place within the EU. If that happens, patients would miss out on new treatments, technologies, and medicines.

Currently, clinical trials are based on national approval – each country needs its own application. But in 2018, the new clinical trials regulation will allow clinical trials applications to be made to encompass all EU countries. That means after Brexit, the UK will be excluded from this single application.

Some companies might not be willing to submit a second application – one to the EU and another to the UK. That could mean the UK is excluded from that particular trial. But it could also mean that the UK incentivizes a UK trial to compete with the EU – for example, by offering a shorter timeline. Again, so much remains unknown, both in the regulations but also in the pro-active response by the UK.

Product Registration

Registering products could be a new issue biotech companies will face, because they will need two separate product registrations, one each for the EU and the UK separately. While the current EU process will remain the same, it is uncertain what that UK registration process will look like.

Under standard regulatory procedures, marketing authorization transfer of a single product may take months to prepare, submit and obtain regulatory approval in all EEA markets. Required variation changes may include a change in MAH and its address, changes in QP release site, changes in the Qualified Person Responsible for Pharmacovigilance (QPPV), as well as changes to multi-country packs. Such changes need to be accepted by every member state in which the product is approved and marketed, and new information needs to be reflected on updated local labelling as well as Patient Information Leaflets.

Changes will affect all products marketed in the EU for which the MAH is located in the UK, irrespective of the procedure under which they were approved for marketing. For example, the United Kingdom was the Reference Member State (RMS) for over 3000 regulatory procedures, and a new RMS will need to be selected for each of the affected marketed products. UK MHRA also played a major role during numerous centralized procedures, and their role will also need to be transferred to agencies in remaining EU Member States.

It is not clear how the regulators and the industry might negotiate to deal with the required changes, in order to avoid serious disruptions in the EEA pharma market next year. The safest way is for each affected company to plan ahead and make the necessary changes on time.

The workload is potentially massive and would come on top of daily responsibilities of regulatory teams in affected companies. For this reason, PRA is offering its support to provide consulting as well as regulatory services to make the required changes on time.

Francisca Burtenshaw
Francisca Burtenshaw (Beloso García) Lic. Fil. Clásica, MCIPD, FRSA Director – Human Resources Western Europe and Nordic Region

So What Does Brexit Mean for CRO Employees?

In order to achieve a successful Brexit transition and keep the focus on key priorities, one of PRA Health Sciences’ first actions was setting up a Global Task Force. Our Director of Human Resources in Western Europe and Nordic Region, Francisca Burtenshaw, explains:

We have developed a stakeholder engagement plan, a communication strategy for each of our stakeholders, which will help to address not only employees’ concerns but also any other stakeholders within PRA who are potentially impacted by Brexit.

We’ve also begun an impact assessment to determine who within PRA is affected by Brexit – and how.

One of the challenges, however, is a lack of clarity on exactly what will be changing and when, since the government is still negotiating these points with the EU. But we will remain flexible and responsive to any changes that arise.

Employees first

One of our focus points is providing support to our employees during this time of transition. We began by identifying and communicating directly by email with all staff who may be personally impacted by Brexit. We carried out a voluntary and confidential survey with our EU workforce in the UK and with the UK workforce in our EU PRA locations to find out our workforce intentions with regards to remain/leave, application for citizenship and/or residence and their family/partners circumstances.

Our Brexit Task Force team will hold Town Hall meetings, both virtually and in person, to provide employees with an explanation and opportunity to ask any questions. Further, our HR UK team will be available for one to one consultation and help with filling applications to remove the risk of a mistake or delay, and reduce stress for the employees.

We’re also sending regular updates to all staff by email when key milestones have been reached by the government.

Anticipating needs

To minimize any unforeseen troubles, we have asked for each department to consider the key risks of Brexit and report them back so we can report the main risks to senior management.

We’ve also asked each department to develop an impact assessment to identify how Brexit may impact our business and what we need to do in response.

We’re still working to ensure impact assessment plans are put in place in all departments affected, and we’re maintaining close review of government updates and our own advisors’ updates so that we keep up to date with decisions made and identify if they impact our business.

Communication and awareness remain key. We’re confident with regular communication to the staff and senior management, and awareness of updates and changes, the transition will be a smooth one.