In light of the withdrawal of the United Kingdom from the European Union, there remain a number of questions regarding medical device and combination product marketing and approval.

Is Great Britain the same as the United Kingdom?
Where do Ireland and Northern Ireland fit in?
With the United Kingdom leaving the European Union, how will this change?
What will be needed going forward since the United Kingdom in the not-too-distant future will stop accepting the CE mark?

At the Xavier Combination Products Summit held virtually in late October, AstraZeneca Global Regulatory Affairs Senior Director for Medical Devices and Combination Products Tim Chesworth spoke about product approvals in the UK, describing the situation as, “something that we need to really keep on our radar because the situation is rapidly changing and evolving at the moment and has a lot of complexity and ambiguity associated with it.”

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He began with a geography lesson to draw a distinction between Great Britain and the United Kingdom (UK). “They are not interchangeable—they are not the same thing,” he emphasized. “The United Kingdom is the United Kingdom of Great Britain and Northern Ireland. Great Britain is a combination of Scotland, England, and Wales. When Northern Ireland is added it becomes the United Kingdom (see Figure 1, an annotated map provided by Chesworth).

Figure 1 Great Britain versus the United Kingdom — FIGURE 1 | Great Britain versus the United Kingdom

The United Kingdom left the European Union at the end of January of this year with a transition period that ends January 1, 2021.

Post transition, the United Kingdom will have its own medical device regulatory system. It will not be part of the European system that applies to the 27 countries in the EU and the other countries in the European Economic Area and Switzerland.

The situation with Northern Ireland is unique, Chesworth explained. Because there is a land border between Northern Ireland and the Republic of Ireland, the regulatory system is going to be different than what exists on the mainland. Chesworth summarized the key changes and differences between the UK and Northern Ireland in a slide, which he annotated (Figure 2).

FIGURE 2 Medical Devices in Great Britain vs. Northern Ireland — FIGURE 2 | Medical Devices in Great Britain vs. Northern Ireland

Great Britain will continue to recognize CE markings until June of 2023, and certificates issued by EU Notified Bodies will continue to be valid up until that point. The UK will introduce Approved Bodies that are analogous to notified bodies, and from that time in 2023 companies will need to place the “UKCA” mark—which means “UK Conformity Assessed”—on the product rather than the CE mark as is done currently. There are also some additional requirements in terms of registering devices as well as placing this new mark on the products.

In Northern Ireland, however, because there has to be retention of alignment between the regulatory system in the rest of the EU and to ensure a frictionless border between Northern Ireland and the Republic of Ireland, effectively the EU MDR will be in effect in Northern Ireland—it will apply from May of 2021 in line with the EU implementation date.

So, the CE mark will continue to be needed in Northern Ireland. They will not accept the United Kingdom’s UKCA mark, “which is interesting, because Northern Ireland is really part of the UK,” Chesworth commented.

“There is also discussion about creating a specific CE UK(NI) mark, particularly for products that are only marketed in Northern Ireland. We will see whether that is actually needed in practice.”

Going Forward

From a legal point of view, legislation is moving its way through the parliamentary system in the UK. The latest phase is now enabling legislation that is being put forward—the Medicines and Medical Devices Bill. “It is hoped that it will achieve royal assent before the end of the year, or certainly before the end of the transition period,” Chesworth said. “At that point, the UK government will have the framework within which to start to make some of these changes and to have control of how medicines and medical devices are going to be regulated once the transition arrangements have ended.”

The result is that in the future the EU MDR will not be retained in the UK because the date of the implementation in 2021 is after the transition period, so it will not be automatically included in the European withdrawal bill. But with the Medicines and Medical Devices Bill, the UK will be able to create its own system.

“I have explained some of the details, but there is a lot more information that will need to come in terms of how it is going to work in practice and specific laws and statutes that need to be put in place to enable things to happen,” the AstraZeneca director pointed out. “There are a lot of unknowns regarding when that is going to happen and what is going to happen. More information is available in the Cumberlege report, which is a key report that is informing a lot of these changes in terms of where things are likely to go.”

In conclusion, he said, “unfortunately, I am going to have to leave you with a lot of questions.”

“What about combination products in the UK going forward? Will the UK adopt Article 117? This is an interesting point because Article 117 in the MDR amends the medicinal products directive. How is that going to be adopted in the UK? It is not just about device regulation in the UK, it is about medicinal product regulation as well.” EU MDR Article 117 introduces significant new practices for drug-device combination product manufacturers. A position paper on the article written by the European Association of Medical Device Notified Bodies is available here.

“Will the UK accept a Notified Body opinion? Will it use some kind of MDR Article 117 approach? We do not know. And potentially, are we going to need to have some kind of Approved Body opinion in the future? We do not know. These are questions I leave you with regarding things we are going to have to monitor over the coming months and years as to how we navigate this system across the United Kingdom, Great Britain, and Northern Ireland and also to see what the future relationship is going to be between the United Kingdom and the European Union.”