Brexit & Regulatory Affairs – The UK Is Heading for the Exit

In an extract from our second Brexit whitepaper, we look at the impact of Brexit on regulatory affairs and issues such as the future of the European Medicines Agency, Pharmacovigilance and Brexit and much more.

Loose Lips Sink Ships

There’s an old American idiom that was used frequently during the Second World War: “Loose Lips Sink Ships”. That’s how Donald Tusk must have felt when he let slip the details of his conversation with Prime Minister Theresa May. By letting everyone know that the newly installed Prime Minister intends to invoke Article 50 of the Lisbon Treaty in the first months of 2017, he pulled the trigger on the race for the exit. There is no doubt that his ‘momentary slip of the tongue’ hastened Prime Minister May’s announcement at the Conservative Party Conference that Britain will seek to invoke Article 50 before the end of the first quarter of 2017. And while at every turn in this fascinating geopolitical intrigue people continue to half heartedly say that there is no going back, we now know that very soon there will certainly be no more time for pleas and second chances.

Since dawn broke over Britain on Friday, June 24th there has been a paucity of new investment announcements, cautious signals about the impact of the decision to leave the EU and a very public media battle between pro and anti Brexit elements.

In the pharmaceutical sector there has been a scramble to decipher possible changes and to seek to calm companies and human talent in the event of the exit becoming a reality. Most notably in all of this, there has been feverish speculation about the future location of the European Medicines Agency. There has been a constant throughput of politicians and lobbyists from across the European Community travelling around seeking to secure the glittering prize of the European Medicines Agency for their bailiwick. In this whitepaper we will look at the endeavours being taken by various governments and city leaders to bring the prestigious agency to a new location.

As the acknowledged Brexit experts in the regulatory affairs sector, we have seen a considerable uplift in enquiries and projects from new and existing client companies around the world since Britain voted to leave the EU. Many companies have moved to guarantee the continued presence of their licensing needs within the EU. There is a consistent thread in a high percentage of these projects; to move the RMS from the UK to a new EU based authority.

Furthermore, our colleagues in the Acorn Regulatory Medical Devices division have experienced an unprecedented increase in new requests from companies across the world seeking to change their EU Authorised Representative from UK to Ireland, or to support the CE marking process of their device in Europe. Despite the increased demands that the new projects have brought we have been handling them in a timely manner. The Acorn Regulatory team has expanded by over 30% in first three quarters of 2016. The increase in staffing is due in no small part to the UK’s decision to leave the EU and the industry’s response to that decision.

In this whitepaper, the second in our Brexit series, we will look at the opportunities that Brexit presents for the life sciences sector. We will also look at the concerns for companies in areas such as regulatory affairs, the ability to attract talent and concerns for the PV sector in the post Brexit world.

As always, our team welcomes any comments that you may have on the thoughts contained herein or any other aspect of our work. I would be delighted to hear from you.

In the meantime, I do hope that you find this informative and useful to you as we move towards Brexit.

Where Next for the European Medicines Agency?

For those of us working in the sector, the future location of the European Medicines Agency has been a consistent topic of conversation since the outcome of the Brexit vote became known. There is no doubt that the UK’s decision to leave has caused some upset for the 600 members of staff at the agency. In a human context, their livelihoods and the location of their employer are now in the air. The EMA is one of a number of agencies that are now being courted actively by European governments in an attempt to persuade them to choose their cities.

The intervention of the Japanese government in early September 2016 brought the EMA issue further into the open and threw down the gauntlet to the British government in relation to current and further Japanese investment in the UK’s life sciences sector. In a 15 page letter, Japanese officials told their counterparts in the UK that if the EMA leaves the UK then the budgets of biopharma companies may follow. The letter stated:

“If the EMA were to transfer to other EU Member States, the appeal of London as an environment for the development of pharmaceuticals would be lost, which could possibly lead to a shift in the flow of R&D funds and personnel to Continental Europe”.

Despite the threat and the large scale of Japanese investment in the sector in the UK, it is unlikely that there will be any acquiescence to their demands. Moderate voices in the UK media are increasingly indicating that we will see a ‘Hard Brexit’ i.e. a move to exit the single market and to restrict the free flow of people into the UK. In this instance, the departure of the EMA from its headquarters in London is all but guaranteed.

But where will it end up? The weeks and months since the June vote have seen a constant trouping of elected officials and representatives from numerous governments in and out of the Canary Wharf headquarters of the agency. Already, a number of countries have moved ‘into the lead’ in the race to land the agency.

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The Future of the EMA

Many see Milan as being the front runner. It’s charismatic Mayor, Giuseppe Sala (pictured right), was one of the first elected officials to meet with officials at the EMA once the outcome of the vote became known. Milan is regarded as Italy’s financial services centre and an ideal location for start up businesses. One of the main reasons that so many cities are seeking this asset is that there is a belief that its presence will incentivise pharmaceutical companies to locate in proximity to the EMA.

To that end, there are reports in Italian media that the Mayor, in association with the embattled Prime Minister Matteo Renzi, will seek to create a tax-free zone in the city in an attempt to entice foreign direct investment from pharmaceutical companies. Milan, it must be argued, is a significant contender, if not the main contender in this endeavour. The country’s pharmaceutical sector is Europe’s second largest in production terms and Italy is the world’s largest exporter of medicines per capita. The city is not just seeking to secure the presence of the EMA in the capital of Lombardy. The Consiglio Comunale are also keen to bring the European Banking Authority to Milan.

The Danish government has also made overtures, albeit obliquely, at this stage. There have been numerous media reports that Danish firm Novo Nordisk has lobbied the Danish government to seek to host the EMA. The country has a track record of hosting such agencies as it currently hosts the European Environment Agency.

Copenhagen faces stiff competition from Stockholm. The Swedish city has already established a working group to manage the projects. Speaking in July of 2016 Anders Lonnberg, the Swedish Life Sciences Coordinator told ‘The Times’ that “you cannot have an agency of the EU if you are not a member”.

Dublin, because of its proximity to the current headquarters, coupled with the fact that Ireland is also an English speaking country is perceived by many as being well placed to host the EMA. Health Minister, Simon Harris TD, speaking at the BioPharma Ambition conference in Dublin Castle in September 2016 said that the Irish Government was ready to submit its bid to host the EMA and that it would be highlighting the excellent R&D and pharmaceutical environment as part of its endeavours. The Minister highlighted the proximity issue as a major advantage in Ireland’s bid to secure the agency for Dublin. He said “given the importance of the work of the agency, it is important that disruption is kept to a minimum when it relocates from London.” Speaking at the same event, Chief Executive of the Irish Pharmaceutical Healthcare Association Oliver O’Connor said that Ireland had a strong case to put to the EMA. “I think that it would be a good addition to the capability that Ireland has already demonstrated on a global scale for manufacturing, development and high regulatory standards” he said.

Frankfurt, Madrid and Lisbon are also actively seeking to host the EMA in their respective cities.

The decision on where the EMA will be located will need to be made very soon. It is expected, as referenced in the introduction, that Article 50 will be triggered in early 2017.

Skills Shortage

The UK pharmaceutical sector employs in excess of seventy thousand people. The structure of a Brexit will have significant impact on them and the industry that they work in. For now, there is a firm belief that the UK will make a full exit from the single market and, with that, there will be restrictions on those seeking to move to the UK. As a sector that is heavily reliant on attracting the right people from all over the world, this is expected to cause major headaches for companies seeking to leverage these talents to grow their businesses.

Even before the development of Brexit, The Association of the British Pharmaceutical Industry had issued a report “Bridging the skills gap in the biopharmaceutical sector” in November 2015 to highlight the paucity of adequately qualified recruits to work with member companies. The report outlined the shortages of qualified staff in areas such as device technology, physical chemistry and pharmacy formulations. The report also noted a shortage of QP’s (Qualified Persons).

The topic of immigration formed the centrepiece to a divisive and often ugly referendum campaign. There is a school of thought that believes that then Prime Minister David Cameron did not do enough to address the issue during the course of the campaign. Many people felt that he did not set forth a positive overview of the benefits of immigration to a country that plays such a part in the global economy.

Now, the UK pharmaceutical industry faces the prospect of a cumbersome immigration process that will deter the most capable candidates. Furthermore, the risk of ‘investment flight’ from the UK as threatened by countries such as Japan, may mean that the most capable candidates will not have the opportunities to work on ambitious R&D projects and they will seek to locate elsewhere in the EU or globally.

‘Brexiteers’ have pointed to the benefits of introducing a points-based system to ensure that those with the skills that are needed can get through the immigration process while those that may be a drain on the resources of the state will be prevented from doing so.

So, what will the UK pharmaceutical sector do? It is obvious that they will have to start thinking differently. A recent report about the impacts of Brexit by The Resolution Foundation suggested that lower skilled jobs would need to be automated and that technology may also need to play a part in the high-paid roles that may no longer be filled. While, for some, this may not seem like an option, the fact remains that a country that already struggled to attract the requisite amount of candidates to fill jobs in a £56 billion per annum industry will now face significant roadblocks.

The issue of free movement has been, for some time, a pillar of the pro-Brexit argument. The overriding assumption in all of the highly charged political arguments is that free movement is a flow of lower-paid individuals.

The end to free movement to the UK from within the EU will cause difficulties for the UK and will, without doubt, see it lose its dominance as a location for R&D as it struggles to attract and bring in leaders in drug development. We now know, that ‘grandfathered’ EU laws will remain in place until such time as the UK decides to draft its own version of the law or repeal it. Therefore, it is safe to assume that all current EU generated laws coupled with the period of time that it will take for the UK to successfully exit the EU, means that there will be no adverse changes in the short term. Longer term, the spectre of changes to free movement will mean that the UK’s ability to attract and retain individuals from outside the UK will be significantly diminished.

Brexit & Pharmacovigilance

The UK’s decision to leave the EU has cast a shadow of uncertainty over many sectors but none more so than the sector that is charged with ensuring patient safety.

Many experts across Europe have speculated that the existing pharmacovigilance arrangement might remain in place in order to maintain commitments to patient safety. But how will this work ? Transition phases in all companies and organisations have a tendency to bring certain issues to the fore and, if a split is engendered, then with the creation of a relocated EMA there may be concerns about patient safety issues ‘falling between the cracks’.

The terms of the Lisbon Treaty state that a departing country must complete the separation process within 2 years, thus, for companies who have an EU-qualified persons responsible for Pharmacovigilance (QPPV) based in the UK there will be a need to relocate or identify a new EU-QPPV. The MHRA are likely to require a local QPPV based in UK. In addition, the MHRA may also require a deputy-QPPV, based in UK or accept an English speaking deputy-QPPV based in another country. For those EU QPPV’s based in the UK, the PSMF will require an update to identify the new location of the EU QPPV at a minimum.

In accordance with Article 57 (2) of Regulation (EC) No 726/2004; a database of medicinal products authorised in the EU was established. This database contains approximately 500,000 medicinal products and is the most comprehensive database of medicinal products authorised in the EU. As of February 1st, 2016, changes in the name and location of the QPPV and changes to the PV system master file (PSMF) could be submitted through the Article 57 database , thereby avoiding the need for a Type IA variation to register these changes. So what effect will Brexit now have on this process? Will a new system be required for the UK, or we will now have to submit a variation to the MHRA for such changes ? Will the MHRA require a PSMF? If so, how will this differ to the EU PSMF?

During September 2015, the medical literature monitoring (MLM) service was introduced. For products containing the active substances already being reviewed by the European Medicines Agency (EMA), the MAH was not required to report to Eurdavigilance any suspected adverse reactions (ADRs) found in the MLM. While the service currently reviews over 300 chemical active substances, many of these substances had significant activity and it has somewhat relieved the burden on MAH’s in relation to reporting requirements.

What will the MHRA now expect of MAH’s for medicinal products containing these same substances in the UK? Surely they will not expect us to report such ADR’s directly to the MHRA? Activities such as this will put extra strain on an already over-stretched department.

It is to be expected that the MHRA will implement specific PV regulations. How different will these be to the current GVP Modules? Irrespective of this, the new PV regulations will require careful assessment of the minor differences and developing customized SOPs for UK authorisations. At this stage it’s difficult to assess the impact on PV fees and work sharing for PSUR and RMP evaluations. This will mainly depend on the arrangement between MHRA and EMA for participation in centralised applications, MRPs and DCPs .

Global collaboration is essential for robust PV. As an example, early identification of signals increase considerably when safety data from all sources are consolidated. The MHRA PV team has always been a strong advocate of a global safety database and has insisted on the reporting of non-EU ICSR’s if reported by healthcare professionals. In fact, global collaboration in PV has been achieved to a certain extent with the help of UMC and the efforts of WHO.

Brexit raises a range of questions for pharmacovigilance experts that are, as of now (October 2016), unanswered:

1) Will GVP guidelines apply in the UK post Brexit?

2) Will the MAH need one QPPV for the EU and another for the UK?

3) Will the MHRA accept the EU PSMF or will they require a separate system?

3) Will the MAH maintain a global safety database, or what will be the reporting structures for newly identified SUSARs, and ADRs?

The pharmacovigilance sector will, perhaps, be the area that sees the most change following the UK’s decision to leave the EU. We are working with new and existing clients to answer questions, such as those listed above, every day. The coming months will see new structures becoming more apparent and with that, some certainty for those working to ensure patient safety.

Find out more about our Brexit services and some of our most recent writing on the issue below.

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CMC & Pharmaceutical Services

Our pharmaceutical regulatory affairs team is staffed by experts who have considerable expertise in the sector. Every team member has at least 15 years of experience in the pharmaceutical sector assisting pharmaceutical companies with their regulatory issues. Since 2002, our pharmaceutical regulatory affairs specialists have been working with clients all over the world. Read more here.