NEW YORK — For makers of in vitro diagnostic tests in the UK, the shape of the market has been changing, and change seems to be the only certainty. British firms have in recent years had to contend not only with the implementation of the new European IVD Regulation and their country's exit from the EU, but the delayed rollout of a new regulatory system within the UK.
Adding to regulatory complexity are domestic economic issues, such as inflation and sustainability targets, which have created further pressures for IVD firms, big and small.
In the face of these challenges, the UK government has made investments that could eventually pay off for the industry, such as a recent £650 million ($830 million) growth package aimed at spurring development in the life sciences sector.
Earlier this year, the government also supported the publication of an IVD Roadmap that highlighted the challenges facing IVD makers, such as a lack of access to domestic funding, as well as a complex route for deploying new technologies within the UK National Health Service.
In general, UK IVD makers have welcomed the regulatory changes, both those covered by the European IVDR and the implementation of a new regulatory regime overseen by the UK Medicines and Healthcare Products Regulatory Agency. The latter will eventually require companies to label products with a UK Conformity Assessed (UKCA) mark to place their IVDs on the market in Great Britain.
Helen Dent, chief operating officer of the British In Vitro Diagnostics Association, or BIVDA, a trade association that represents IVD companies that supply tests to the UK, said the sector has experienced "difficulty" not only because of evolving regulations but also because companies are now under pressure from diverse factors. These include meeting certain government policy objectives, as well as inflation, which has been hovering around 10 percent in recent months in the UK.
Companies are therefore trying to balance the costs of making their diagnostic products compliant with the cost of doing business, plus meeting targets for the government's net zero strategy, for example, which aims to decarbonize all industries by 2050.
"While the government is keen to invest in the industry, the costs to do so need to be considered for the UK to be an attractive place to do business," Dent said.
Ashleigh Batchen, head of regulatory affairs at BIVDA, also noted that the future regulatory system in the UK is still being put in place. Following the UK's exit from the EU, EU law, including the IVDR, implemented after this departure will no longer apply in Great Britain. That means that the UK has to devise its own system for certifying medical devices and IVDs.
Initially, the UK intended to require IVD firms to obtain UKCA certificates for their products by this July. However that date was postponed at the end of last year to July 2024, and last month, the government pushed back the date again, to July 1, 2025.
It should be noted that these changes only impact the placement of tests on the market in Great Britain, which includes England, Scotland, and Wales. In Northern Ireland, companies do not need to obtain a UKCA mark to sell their tests due to the Northern Ireland Protocol and must continue to obtain compliance with EU regulations.
The government did hold a public consultation with the medtech community related to its new regulations in 2021. However, as Batchen pointed out, so far, the industry has only received guidance from the government, but no regulations are in place.
"We are in the midst of finding out exactly what the new requirements will be for IVDs in Great Britain," she said. "In contrast to the EU, we have not yet had publication of the new regulatory framework and are instead relying on the UK government’s consultation response summarizing their intentions for the future regime," she said.
Batchen added that while it appears that requirements to obtain a UKCA marking will be similar to those for gaining compliance with the IVDR, there "remains a lot of uncertainty" with these changes.
She also agreed with Dent that this ongoing regulatory complexity, coupled with environmental and social pressures, have made it a "difficult time for the IVD industry," and that companies have had to reconsider their market strategies because of it.
Take Belfast-based diagnostic firm GenoMe Diagnostics, for example. The firm is developing a digital PCR-based early-stage ovarian cancer detection test called OvaMe. In March, its chairman, Mark Street-Docherty, who is also the CEO of Bristol-based Rosa Biotech, said GenoMe elected to pursue US Food and Drug Administration clearance for the test, rather than IVDR or UK approvals due in part to uncertainties related to the implementation of those new regulations.
"IVD businesses are looking further afield to other attractive markets, which have better defined regulatory practices," Street-Docherty commented recently. "For many this will be the US."
He added that the implementation of new regulatory regimes in the EU and UK has "certainly increased the cost and time to market for all innovative IVDs" in the UK. Given these new circumstances, small and midsized enterprises will have a "higher requirement for working capital and should expect it to take longer to generate first revenues," he said.
One spot of sunshine in what can sometimes seem like a perpetually gloomy British landscape is a decision last month by the UK to allow devices holding CE-IVD marks to remain on the market until the expiration of the certificate or by June 30, 2030, whichever comes first. The same goes for IVDs holding an IVDR certificate, which also will be able to remain on the market through June 2030. After those dates, all tests will be expected to also be UKCA marked.
Street-Docherty said that these decisions will free up resources within UK-approved bodies, as well as EU-notified bodies, to assess new tests, rather than to reassess tests that held certificates obtained under another regulatory framework and merely need updated certification to remain in compliance and on the market.
And for UK firms that seek to sell their tests in Europe, Street-Docherty said that there are now more designated notified bodies able to handle submissions, which has reduced bottlenecks for obtaining certification under the IVDR. A shortage of NBs has challenged the implementation of the IVDR, causing the EU to stagger grace periods for different classes of tests through 2028.
Of course, this is just the current constellation of regulatory factors facing UK firms, and at times, it can seem to industry observers that the facts on the ground can change on a near daily basis.
In its latest update to members, the Association of British HealthTech Industries (ABHI) in its July 7 letter drew attention to MHRA's new corporate plan for 2023 to 2026, which foresees creating product registration equivalence routes for other jurisdictions such as the EU and US.
According to Stephen Lee, director of diagnostics regulation at ABHI, a public consultation on regulation for recognizing devices cleared outside the UK is scheduled for October. Lee remarked that UK IVD firms are facing a "rapidly evolving regulatory landscape" and noted that MHRA's decision to delay the implementation of core aspects of the new system until 2025 will give the agency two more years or more to set up the new regulatory framework.
The investment element
While the regulatory situation in the UK can seem harrowing, the government has tried to support innovation in a variety of ways.
Street-Docherty noted the recent £650 million Life Sciences Growth Package can help alleviate some of the pressures on companies, particularly small and midsized enterprises. Part of the package includes a £150 million investment in the UK Biobank, which Street-Docherty called a "positive step in the right direction" for IVD companies, as it will reduce the time and cost of acquiring data for test development.
"Acquisition time and costs of clinically relevant development materials currently represents a significant barrier to the speed of innovation, development, and technology deployment, particularly for those in the industry with a requirement for large well-defined clinical datasets," said Street-Docherty.
Joe Fitchett, senior adviser for biotechnology at the Institut Pasteur in Dakar, Senegal, and a former medical director for Mologic, said such investments are welcome but also said they were "long overdue" and "at risk, given the number of prime ministers and revolving door of ministers" that the UK has experienced in recent years.
"Science in itself is a roller coaster of progress and pitfalls, best navigated when at least the funding and infrastructure to support the science ecosystem are stable to encourage discovery and development," said Fitchett.
Another UK government undertaking that has the potential to support companies is the Long-term Investment for Technology and Science (LIFTS) initiative, announced this year, which will use £500 million to support new funds that, complemented with other investments, can be channeled into science and technology businesses.
Street-Docherty said that LIFTS "has the potential to act as a catalyst to shift investment quantum in UK life sciences as a whole," and noted that the initiative will help British companies cut their reliance on US and other capital sources, a vulnerability identified in the IVD Roadmap published earlier this year.
There have been other investments in recent months, including a £36 million investment from the government into Randox, the Crumlin, UK-based IVD manufacturer, through the Life Sciences Innovative Manufacturing Fund to modernize the manufacturing of antibodies used in its tests. In May, the government also announced an investment of £2.3 billion to open 160 community diagnostic centers around the UK.
Last December, the UK Department of Health and Social Care also invested £175 million in genomic research, the bulk of which will support using whole-genome sequencing to diagnose newborns with genetic conditions. Genomics England is leading the newborn project, and CSO Matt Brown said this week that the company is "delighted to see the government’s ongoing commitment to building the life sciences sector, which will bring both economic and health benefits to the UK."
According to ABHI's Lee, more of such investments are only welcome.
"The government must continue to invest in diagnostics capacity and capability to meet increasing demand and shift our healthcare system to detecting diseases sooner," Lee said. "And it is beyond doubt that early diagnosis results in better outcomes and lower overall costs."
The impact of COVID-19
According to Adrian Smith, CEO of Oxford Gene Technology, another factor that forced change in the UK IVD market was the COVID-19 pandemic. "We saw improved access and faster decision-making by the UK government and the NHS," Smith said of the UK's response to the pandemic. As global players worked to serve their home markets, especially earlier on in the pandemic when the supply chain was under pressure, the UK government turned to the domestic IVD sector to meet demand.
"It will be interesting to see how the UK government, having realized the importance of a local IVD sector during COVID, acts to support and sustain this sector in the future," said Smith, who also sits on the board of DRW, a Cambridge-based IVD company.
He also expressed hope that the new UKCA regulatory framework would align with major existing regulatory systems, such as the European IVDR and the FDA. "It's in nobody's interest to burden the IVD industry with significant additional cost for a UKCA certification," Smith said.
There is also the issue of certifying tests that rely on newer technologies, such as next-generation sequencing or artificial intelligence. Later this year, the UK is set to establish a new pathway for regulating such tests, called the Innovative Devices Access Pathway. The service, which will help steward new IVDs into use by the NHS, is being created by MHRA, and the UK National Institute for Health and Care Excellence.
"As IVD technologies rapidly advance, regulatory systems will need to accommodate these advances to ensure quality and safety without stifling innovation," said Smith. "The important thing is that industry, regulators, and notified bodies continue a dialogue throughout the process," he said.