Access denied: Is Brexit spelling bedlam for UK clinical trials?

pharmafile | February 1, 2022 | Feature | |   

Since Article 50 was triggered on the 29 March 2017, the UK’s pharmaceutical industry collectively held its breath, bracing itself for the anticipated impact of leaving the EU. Then-prime minister Theresa May faced a new wave of pressure from those on both sides of the fence, attempting to find a compromise between Labour’s calls for a second referendum, and the Conservative Party’s fervent desires for a laissez-faire approach. This turbulent time has provoked many questions: what complications does Brexit present for clinical trials, and what knock-on effect is this likely to have on regulatory approvals and the distribution of medicines?

Back in February 2016, four months after the referendum vote, the UK Office for National Statistics said sales of British goods to the EU fell 8%, to a six-year low of £134 billion in 2015. Figures have shown that goods imports from Great Britain have dropped by over a fifth since Brexit, and latest figures from the Central Statistics Office (CSO) show that the value of goods imports from Great Britain fell by almost €3.3 from January to November 20211. Smaller EU countries, such as Finland, Luxembourg, and Portugal, are among those who have benefitted from Britain’s departure from the EU, as they fill up the spots of Brexit exporters outside the EU. But what exactly has changed for the UK?

According to a 2019 article by Noerr, titled ‘Clinical trials in the United Kingdom after Brexit’, the UK’s withdrawal from the EU means that standards laid down by European law for conducting clinical trials, in particular the Clinical Trials Directive and the Clinical Trials Regulation, as well as the Guideline for Good Clinical Practice, no longer directly apply in the UK. If a European authorisation (MRP/DCP or central authorisation) of the medicinal product is desired following the clinical trial, the applicability of the relevant European regulations should be expressly provided for in the contract for the clinical trial with the British Investigator. This should be taken into consideration when drafting new contracts and, if possible, integrated into existing contracts.

While the UK is no longer subject to approval from the EMA, the MHRA is still aligned with the EMA, meaning that the UK can supply medicines to countries in the EU without significant cost and inhibition to market access. Fortunately, this diminishes the extent to which pharma companies will have to adapt.  


On reflection

Brexit was officially actioned on the 31 January 2020, marking the UK’s exit from the EU single market and customs union. This provoked unease throughout the healthcare sector, and more specifically, the pharma industry, as companies prepared for more convoluted regulations, wondering about the uncertain future of clinical trial pathways.

In December 2021, the European Commission (EC) set out plans to help prevent Brexit disrupting the supply of drugs in certain markets, most notably to Northern Ireland. Northern Ireland, which is part of the UK, is subject to EU regulations. This has presented certain complications, such as when a drug became available in England, Scotland, and Wales before Northern Ireland. The end of transitional arrangements threatens to cause shortages by erecting regulatory barriers in the Irish Sea. Pharma companies already have a foothold in the Republic of Ireland, they may actually decide to strengthen this in the aftermath of Brexit, but this is not without difficulties.


Legally bound: how will Brexit impact UK clinical trials?

Clinical trials are multifaceted, big-budget projects, and sponsors are necessary to assist in the processes of initiation, management, and financing. Whilst the process may remain largely unaffected, there are notable complications surrounding supply of clinical trial material – images of lorry queues at the Port of Dover illustrate one example of Brexit’s knock-on effect to the supply chain. From now, clinical trials conducted within the UK will require the designation of a British sponsor, meaning that it may be necessary to appoint two different sponsors for the same clinical trial. Despite this, the UK has announced that it may recognise sponsors from certain member state countries in the EU as sponsors for clinical trials.

The Medicines and Medical Devices Bill, published on 4 September 2020, enables EU Directives to be transposed into UK law through secondary legislation. The Bill seeks to address the regulatory gap through introducing regulation-making, delegated powers covering the fields of human medicines and medical devices. In the realm of patient recruitment, the MHRA noted that the Bill is currently going through parliament would “enable legislative changes to do what’s best for the UK, to support innovation and protect patients. These powers will also enable transparency to support patient safety work. Clinical investigations work will be part of these future considerations.” However, the body does not have any definitive timescales at this stage. According to the MHRA press office, the body is currently required to adhere to Article 20 of the Medical Device Directive, which is restrictive on the publication of any commercial data.

Speaking to Pharmafocus, Dr Thomas Lonngren, Strategic Advisor, NDA Group, commented, “The UK is still attracting companies to carry out their clinical trials, due to the MHRA, NHS, R&D innovation and infrastructure, and access to patients. From a regulatory point of view, very little has changed with regards to approvals of clinical trials, the most notable is that the MHRA has introduced rapid procedures to approve clinical trials.”


A bundle of nerves: What challenges are pharma companies encountering?

Brexit has triggered concerns about distribution logistics, and the costs associated with this.  According to a 2019 article published by Noerr, a wholesale distribution authorisation is required in order to place medicinal products on the market in the territory of the EU as a wholesale distributor. This means that British pharma companies that own this could, in principle, continue to engage in the wholesale distribution of medicinal products from the UK to EU member states. On the other hand, further complications could arise for companies that are not in possession of a licence.

British research institutes and potential sponsors of clinical trials rely on a quickfire exchange of information, but they could face challenges in accessing data published in the EU database. As highlighted in a 2020 article by Hannah Balfour (European Pharmaceutical Review), a no-deal Brexit poses the threat of increased counterfeit medicines, which is being heightened through difficulties accessing vital information. Pharma companies are being urged to review their anti-counterfeiting strategies ahead of time, as according to the International Hologram Manufacturers Association (IHMA), the UK is likely to see a surge in counterfeit medicines, after the EU’s FMD ceased to apply at the end of the Brexit transition period. The FMD uses mandatory safety features and an EU-wide database to help prevent the distribution and sale of counterfeit medicines which could pose a risk to patients.

Back in 2020, Dr Paul Dunn, chair of the IHMA, substantiated widespread concerns: “Failure to secure a Brexit deal could leave the door wide open to crafty criminals, who are infiltrating global supply channels, deploying scams and counterfeiting measures to trick consumers and damage manufacturers.”

As Brexit will undeniably impact medicine distribution, this could also inhibit patient access to treatment. Dr Thomas Longgren, Strategic Advisor, NDA Group, said, “There is a risk that companies will choose the US and EU as their first market for regulatory approval, and will defer approval in the UK and the other markets. This could be the case with smaller biotech companies that don’t have the regulatory expertise to manage regulatory approvals in several markets simultaneously. This could lead to a delay of new medicines being introduced into the UK market.

“The UK no longer benefits from being part of the EU regulatory system or the single market, however from a regulatory perspective if the UK adheres to EU regulatory standards, supplying, and distribution to the EU should not be a problem, aside from the extra steps needed regarding importation controls and regulatory approval in the EU.”  


No risk, no reward: What can pharma companies do to mitigate these?

One way to combat the increased threat of counterfeit products, as shared by the IHMA, is through the use of well-designed and properly deployed authentication or serialisation solutions, which enable examiners to verify the authenticity of a legitimate product. This would mean that even those carrying a ‘fake’ authentication feature can be distinguished from a genuine item.

Back in 2021, Pharmafocus spoke to Dr Pius Waldmeier from Roche, who expressed the effectiveness of serialisation in diminishing the risk of counterfeiting: “Serialised or digitalised products improve visibility and security in supply and distribution chains, and make it easier to track our medical products, and to prevent counterfeit and falsified products entering the supply chain. Roche has also been working with other pharmaceutical manufacturers to promote a serialisation solution in Europe and many other countries, which enables pharmacists to compare a unique number on each pack of medicines against a central database to confirm its legitimacy. In countries where serialisation is strictly applied (often driven by government) and seriously used for verification, counterfeit products are scarce.”

As of 1 January 2021, end users in Great Britain were disconnected automatically from the UK National Medicines Verification System (UKMVS) run by SecurMed UK. This means that it is no longer possible to verify and authenticate packs. However, integrated pharmacy systems can still use batch details, expiry dates, or product details from packs’ 2D barcodes while these packs are still in circulation. However, pack serial numbers no longer have any function, according to guidance from the British Medical Association (BMA). The government will first be required to consult with industry stakeholders, including pharmacy organisations, before introducing any new regulations. Despite this, no timetable has been set by the government for consultation.

According to NDA, “Ideally, companies will be responsible and not delay approval of their new drugs in the UK. The UK government and MHRA have introduced a new set of procedures for marketing approval that will encourage companies to interact with the MHRA early during development, resulting in faster approval and market access. Pharmaceutical companies welcome these new procedures, and the uptake so far seems promising. Some companies may decide to select the UK before the EU, for market approval; it’s too early to say if these measures will mitigate the fact that the UK is not part of the EU regulatory system.”   

Brexit may have thrown pharma companies off their familiar course by raising a plethora of questions in its wake, but as we have addressed, there are approaches that pharma companies can adopt to alleviate this burden. The Medicines and Medical Devices Bill introduces an alternative avenue, minimising effort for companies, by offering secondary legislation and preserving the EU laws that have long cemented their place in the UK’s regulatory system.

Lina Adams



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