Current Event Analysis: Brexit, Clinical Trials and Regulations

More than three years have passed since Brexit, the referendum in which the UK voted to leave the European Union. Since then, the country has been through two prime ministers and missed the first Brexit deadline. With Boris Johnson now leading the country towards the new exit deadline of October 31, 2019, the UK is at a stalemate as to whether it will be leaving the EU without any defined trade deal. 

The so-called no-deal Brexit poses a number of serious issues for all industries. But for the clinical research industry, patients’ wellbeing is at risk — and that includes those patients likely excluded from future research as well as those currently enrolled in multinational trials. After all, regulations may no longer be applicable, data standards could be incompatible and global partners are already considering the UK a potentially problematic research partner.

In this post, we explore the possible impacts that Brexit could have on clinical research in the UK and beyond.

UK Trials Drop in Number

The number of trials in the UK has dropped by 25 percent between 2009 and 2017, with the reason for the decline being a lack of clarity over the UK’s future in research. An example is UK patients being dropped from a trial testing a new drug for heart attacks. Health correspondent Alex Matthews-King reports that the U.S. company developing the drug is worried about uncertainties regarding registering new medicines after Brexit.

Another concern is whether data from UK trials will be accepted by the European Medicines Agency. Fortunately, the EMA says the UK will be bound by EU rules during a post-Brexit transition phase to provide business continuity to stakeholders, writes Melissa Wollerman at IMARC Research. 

A key concern is whether the EU’s Clinical Trials Regulation (CTR), which is set for implementation in 2020, will come into effect before the transition period concludes. If it does, then the CTR will be followed in the UK. Even if it does not fit the timeframe, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) says it will try to adopt CTR. Wollerman notes that details of how this will work are unclear and suggests the UK may struggle with it in the future.

UK Considered Unfavorable Partners

Changes have already been felt amid the Brexit uncertainty. One major concern is a lack of willingness from European and international research partners to engage with UK-based teams. The University of Birmingham, at which Professor Pamela Kearns heads up the Cancer Research UK clinical trial unit, is sponsoring 16 clinical trials in 21 European countries but partners are increasingly regarding the involvement of UK teams as risky. 

Kearns says that Brexit might mean that the UK can no longer participate in the European Commission’s 100 billion euro research funding program, Horizon Europe. The UK would essentially be left out of the collective research and funding to treat cancer. 

U.S.-based biotech companies have also expressed concern over future partnerships with the UK after Brexit. Anna Smith at Pharma Times reports that 52 percent of U.S. biotech executives surveyed think the UK will be a less attractive location for future trials.

Brexit clinical trials

Sponsors Need Legal Representatives in the Region

Clinical trials in the UK are managed by the MHRA while trials in the EU are run by the EU Medicines Regulatory Network (EMRN). UK-based trials share some trial requirements and responsibilities with the EMRN, which dictates that a sponsor of a clinical trial in the EU needs to be based in the region or have a legal representative in its place. 

So after Brexit, trials being conducted across Europe and the UK would require UK companies to appoint a legal representative in one of the EU member states and EU sponsors to appoint a representative in the UK, explains Professor Sir Robert Lechler, president of The Academy of Medical Sciences. The effect would be significant, with hundreds of Pan-European trials currently underway. 

Lechler points out that this could lead to chasms between various potential international research collaborations. The divide could also have an impact on the research into rare diseases, which depends on a collective approach that transcends borders. Knowledge needs to be maximized and shared. Brexit could well deny UK patients access to these rare disease research networks.

Furthermore, the requirement of embedding legal representatives in both the EU and the UK would also mean research companies lacking presence in both regions would be unfairly affected, writes Connie Anker at the PHG Foundation of the University of Cambridge. 

Changing Marketing Requirements 

The requirement for a geographically-placed legal representative is also a concern for centrally authorized products (CAPs). The MHRA has told marketing authorization holders of CAPs that the products will be automatically converted to UK marketing authorizations after Brexit unless marketing authorization holders (MAHs) opt out, explain Hannah Kerr-Peterson and Jackie Mulryne at the law firm Arnold & Porter.

MAHs will have one year from the date of Brexit to inform the MHRA of all CAP data, which will be used for update variations and post-authorization submissions. 

Kerr-Peterson and Mulryne say that MAHs with UK-based marketing authorizations will need to have a legal presence in the UK by the end of 2020. To ensure this, MAHs need to appoint a UK-qualified person for pharmacovigilance. 

Loss of Access to Data and Applicability of Standards

The UK will likely lose access to the EU clinical trial portal and database. The consequence for UK-based research institutes and sponsors will be dire as they will desperately need to participate in the rapid exchange of information, write Evelyn Schulz and Susann Jahn at pan-European law firm Noerr. 

But Brexit could also mean that EU standards — the Clinical Trials Directive, CTR and Guideline for Good Clinical Practice — will no longer apply in the UK. This means that should European or central authorization be required for a medicinal product, UK-based companies will need to stipulate in their contracts and with the British investigator the applicability of the relevant European regulations.

Brexit clinical trials

Transit Concerns Could Impact Patient Access to Treatment

Brexit, particularly the no-deal scenario currently being touted as a strong reality, could affect patients who are participating in ongoing trials. The change will likely disrupt shipments of investigational medical products and patients could miss their doses, explains Paul Hegwood, president of clinical supply services at Catalent.

Hegwood says drug development companies are trying to avoid this potential calamity and, where possible, shift investigational medicinal products (IMPs) from the UK to other sites. But other companies are waiting to see what will happen, which Hegwood says will cause a spike in activity once a clear decision has been made post Brexit. 

IMPs going from the Republic of Ireland and the EU may need to be tested again after passing through the UK. These products will then need to be reimported into the EU, notes Bruno Speder, head of clinical regulatory affairs and consultancy at SGS Clinical Research.

There will also likely be increased tariffs and custom requirements too. Speder warns clinical trial professionals dealing with the supply chain and quality control to take action: Increase stock, and consider alternative supply routes and sites.

Indeed, supply chain partners will prove important for pharma companies looking to comply with Brexit. Many of these companies already outsource services and can use these relationships to their advantage. 

Pharma company Almac was considering the Brexit effects and how it would deal with supply chain demands since the 2016 announcement of the UK’s decision to leave the EU, writes Charlie Abrines at Clinical Trials Arena. In fact, the company completed construction of its packaging site in Ireland early in 2019 so it can better package and ship trial supplies to other EU member states.

An Alternative Viewpoint: Brexit Could Bring Positive Change

Brexit hasn’t been all bad news. It might have even been good for the UK’s Office for Life Sciences, NHS England, the National Institute for Health Research and the MHRA. As James Brook, head of UK and Ireland clinical delivery at IQVIA, says: “Brexit has been a positive catalyst for change in the clinical research environment in the UK. It has led to a significant increase in the focus on the commercial research activity and the value of commercial research activity to UK Plc.”

Brook says that the challenge of Brexit — the UK trying to secure long-term investment in clinical trials — has led to improved engagement among clinical research stakeholders including pharma companies, biotechs and CROs. Evidence of Brook’s optimism includes the creation of UK Life Science Sector Deal in December 2017 (after the Brexit referendum), which has focused investment in new areas such as genomics and digital technology. 

The future of clinical research in the UK remains unclear and international partners will likely reconsider their involvement with the nation. But international and non-UK pharma companies committed to global research should look to their supply chain partners to comply with Brexit’s potentially changing regulatory demands.

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