NEW YORK (GenomeWeb) – A major shift in the way in vitro diagnostics are cleared is underway in Europe but companies that do business in the UK must confront additional questions about how British authorities will regulate IVDs once the country leaves the European Union in March 2019.
By 2022, test makers are expected to bring their entire catalogs into compliance with a new European Commission directive regulating IVDs. While stakeholders hope that the UK will continue to accept the CE-IVD mark after Brexit, the issue is unresolved, leaving firms in the dark as to what the future may bring.
"As a business, we are trying to remain open-minded and proactive to respond to the market as the details unfold," said Mark Street-Docherty, CEO of Manchester-based Elucigene Diagnostics. "We are monitoring this closely, as I expect are all UK businesses," he said, adding that "this is a really difficult area to comment on at the moment, given the unknowns."
UK regulators also don't know what will happen, even as they assuage test makers that, whatever deal the UK will eventually make with the EU on the theme of regulations, it is the government's stated priority to limit any disruptions to the market, or to the quality of British healthcare.
John Wilkinson, director of devices at the UK Medicines & Healthcare Products Regulatory Agency (MHRA), the arm of the country's Department of Health responsible for ensuring the safety of medicines and medical devices, said that within the UK, regulators are proceeding as if the UK will continue to follow the new IVD directive after Brexit.
“Our role in regulating medical devices and in vitro diagnostic devices does not change," said Wilkinson. "Our preparations to implement proposed new regulations for medical devices and IVDs continue."
MHRA oversees the work of the UK's five notified bodies (NBs), the organizations that, under the new IVD directive, will assess most IVDs for regulatory conformity before clearing them for clinical use. Under the old IVD directive, most molecular tests were self-certified, meaning that companies could prepare and sell their tests without direct regulatory oversight.
Not only is the UK, with a population of 66 million, a major consumer of IVDs, but its NBs have been responsible for assessing "a large proportion" of devices placed on the EU market, Wilkinson noted. The country is therefore interested in preserving the symbiotic relationship between the UK and the EU going forward. Though details of the relationship regarding regulatory questions are yet to be determined, Wilkinson said the UK is "committed to continue collaborating with the European network."
He added that the current government also laid out three principles that will underpin the development of a post-Brexit regulatory system for IVDs. These are the principle that patients should not be disadvantaged, innovators should be able to access the UK market as quickly and simply as possible, and the UK will "continue to play a leading role in both Europe and the world" in promoting public health.
"While negotiations continue, we will continue to collaborate with all involved to deliver the current speed of authorizations, [as well as] access to new and innovative medicines, medical devices, and IVDs," Wilkinson said.
Simon Richards, chairman of the British In Vitro Diagnostics Association (BIVDA), praised the MHRA for repeatedly raising the issue of IVD regulation with the UK government during the ongoing negotiations. Richards is also regional vice president of regulatory affairs for Europe and the Middle East at Alere, which Abbott acquired last month. He stressed that he was making his comments on behalf of BIVDA, which represents the UK IVD industry, including manufacturers and distributors.
According to Richards, BIVDA is pressing for a mutual recognition of NBs in the UK and those in the EU, meaning that a test CE-IVD marked in the UK post-Brexit will be recognized as conforming to existing regulatory standards in the EU. The association, which has around 150 members, made the same argument in its report The Value of IVDs, which it released last month.
In a second document accompanying the report, BIVDA noted what was at stake for the UK, where IVDs were estimated to contribute £730 million ($958 million) to the UK economy in 2014. The country is also a net exporter of IVDs, which accounted for £1.1 billion ($1.4 billion) in sales worldwide in 2013. As such, BIVDA argued that it was "vital" for the UK to ensure that its IVD and life sciences environment "remains as attractive as possible," not only for the benefit of the economy, but of the National Health Service and patients.
"We strongly urge the Government to align with the EU IVD Regulation and, if possible, retain notified body and competent authority status to allow the EU or UK authorities to mutually accept devices lawfully marketed in other territories," BIVDA said.
Richards noted that Switzerland, among other countries, currently operates within such a framework, and that aligning with EU regulation would ensure stability as the UK exits the EU, while allowing the UK to rely on existing resources to monitor new tests, rather than having to build a new regulatory system from scratch.
Such a scenario of mutual recognition would be ideal for the UK IVD industry because existing NBs with experience could be used to clear tests, Richards said. "That is not guaranteed though," he cautioned. However, any option that resulted in European non-recognition of the decisions of British NBs would also negatively impact the European market, he said, as the UK's NBs are some of the busiest in the region.
While the will to align the British regulatory environment after Brexit with the European IVD directive exists, the fact that no agreement has been reached, and no legislation passed to support it, has raised some concerns among BIVDA members, Richards acknowledged.
"At the end of the day, there are many unknowns, and obviously, from a business point of view, unknown is not good," he said. "The expectation is that we will have no clarity until later in 2018." By that point, the British government will also have a better idea of what new laws will be necessary to implement such a mutual recognition approach, he added.
While there is no clarity yet on what agreement will be reached between the UK and EU, BIVDA is proceeding as if the new IVD directive will continue to be observed following Brexit, organizing seminars to educate members, and training regulatory affairs specialists at firms on how to comply with EU legislation.
"At the end of the day, those regulations will still apply in 27 countries across the EU," said Richards. "It's one of the things where you really need to be on top of that anyway," he said. "To regulators, I would say, 'We really need mutual recognition and as easy a regulatory alignment as possible'."
As for companies operating in an environment where not only EU regulations concerning IVDs have changed, but there is a possibility for disruption related to Brexit, Richards said they should "stay aware" of the situation as it unfolds.
"Fundamentally, it comes down to one country," said Richards. "They will continue to meet the [European] IVD requirements," he said. "It may ultimately be that MHRA could say that if you meet those requirements, they will be British requirements."
Dirk Stynen, president and chief consultant for Qarad, a Geel, Belgium-based company that helps test providers bring their IVD products in line with European regulations, said that the fate of British IVD regulation hinges on whether or not the UK can reach a deal with the EU similar to the agreements the EU has with Iceland, Norway, Liechtenstein, Switzerland, and Turkey.
"These non-EU member states operate under these regulations as if they were members of the EU," he said. "If the outcome is that the UK will have a status similar to those countries, essentially nothing will change."
However, if no agreement is reached, a scenario which has been termed a "hard Brexit," where the UK exits the EU in March 2019 without a deal in place, the country could be treated similarly to other countries outside of Europe, such as the US or the Russian Federation. UK firms, in such a scenario, would have to appoint an authorized representative within the EU to act as a communication link with authorities in the countries where they seek regulatory clearance.
Qarad is an authorized representative for about 70 companies.
"The same is true for [UK-based] NBs," noted Stynen. In the case of a hard Brexit, it would mean that organizations holding NB status for EU directives would have to relocate to the EU, as would authorized representatives, he said. "They would have to either stop offering their services or move to an address in the EU."
In the case of a hard Brexit, UK authorities will also have to decide if they want to install their own regulatory system, or whether they will accept the CE-IVD mark unilaterally, like countries such as Serbia or Montenegro do. Yet even if they decided to design their own regulatory system, it likely won't be implemented overnight, Stynen noted.
"I think it is unfeasible for a member state from one day to another to decide they wouldn't accept the CE-IVD mark anymore, because there wouldn't be any products on the market," he said.
Richards noted that any additional regulations imposed by the UK could impact investment decisions by global players after Brexit.
"The question is where you would best put your development spend," said Richards. "At the moment, there is certainly the risk that the focus would still be on Europe, but Europe without the UK," he said. "I think the UK would be pushed down on the development agenda, or the sales and marketing agenda, because there will be extra requirements if there is not that mutual recognition."
He also said that new regulations could lead to a reduction in the number of tests on the market in the UK, as manufacturers cut products from their menus, a situation that is already underway as companies grapple with the new European IVD directive.
"The cost of the new regulations, and if there are any further costs, is something that will push manufacturers to really look at products and say 'it's not cost effective to bring them to the level of data required under the regulation'," said Richards. "Because of that, products are not going to survive."
While such scenarios are hypothetical, Stynen, like Richards, urged companies to monitor the situation as it changes, but not to panic.
"I would recommend they stay alert," said Stynen. "Since it isn't clear what will happen at the end of Brexit negotiations, I would at least wait another six months before getting nervous."