NEW YORK – The past year has been vexing for European in vitro diagnostics companies, but IVD manufacturers are hoping questions related to the UK's pending exit from the European Union, as well as the new European IVD Regulation, will soon be resolved.
The UK voted to leave the EU in 2016 and was originally scheduled to leave in March 2019, but political deadlock prevented the passage of any deal until current Prime Minister Boris Johnson's Conservative Party won an electoral majority in an election in December. Currently, the UK — the third largest country in the EU — is expected to leave the union by the end of January. Laws governing its regulatory relationship with the EU in the future have not yet been agreed, though.
Concurrent with the uncertainty introduced by Brexit has been the new IVDR, which is slated to come into effect in May 2022. Under the IVDR, most IVDs that were previously self-certified must be cleared by a designated organization called a notified body or NB. However, no NB was designated under IVDR until the end of 2019, stoking fears of a regulatory bottleneck as companies work to get thousands of tests cleared by a handful of NBs by the 2022 deadline.
Some of the leading European NBs meantime have decided to stop certifying IVDs altogether. Coupled with questions about the UK's future status, it's created uncertainty for the IVD industry.
"For the IVD industry in the UK, 2019 was a difficult year filled with uncertainty," said Doris-Ann Williams, head of the British In Vitro Diagnostics Association, which represents UK IVD makers. She said the regulatory changes related to the IVDR as well as Brexit had contributed to these concerns.
With regard to the IVDR, she specifically cited a lack of readiness for implementing the new regulation. One issue has been the availability, or lack of, of the European database on medical devices, or Eudamed, which is integral to the IVDR for registering new tests, as well as providing information on their regulatory status, performance data, and post-market surveillance information.
Though Eudamed was supposed to be ready for use by May 2020, when the new European Medical Device Regulation (MDR) comes into effect, the European Commission in October delayed the roll out of the upgraded database until May 2022 citing technical challenges.
Another issue has been a lack of NB capacity to clear IVDs. In October, Dekra, a German safety organization, became the first NB to be designated under the IVDR. BSI's UK office also became designated for the IVDR that month, and its Dutch subsidiary, BSI Netherlands, was designated in December.
While industry welcomed the designation of several NBs to assess tests under the IVDR, industry observers have noted that 21 NBs were designated under the previous regulation, 1998's IVD Directive, and that less than a dozen have applied for IVDR designation. Moreover, some of the NBs with the greatest capacity for certifying tests — Lloyd's Register Quality Assurance and UL — decided to exit the market completely.
Complicating matters is the fact that once the UK leaves the EU, NBs will need an office in an EU member state to clear tests under the IVDR. This might result in a situation where UK companies will need to have their IVDs cleared in the Netherlands, for example, so that they can sell them not only in Europe but back into the UK. Authorities there have said previously they would like to harmonize their regulatory regime with the EU after Brexit to enable the sale of tests into and out of the UK.
"The industry's position is that we would like the UK to be able to access the EU after we exit on Jan. 31, 2020, or at least to have an identical law for IVDs in the UK," said Williams. "This would continue to guarantee safety for patients and to prevent UK companies from having to deal with yet another regulatory system, even if this was to [have a] lighter touch than in the EU," she said.
Williams added that even if the European regulatory regime remains more or less in place following Brexit, the work of complying with the IVDR is still "substantial and both huge in terms of financial and manpower resources." She acknowledged, however, that the election of a majority government last month at least has provided certainty around the UK leaving the EU.
Pat Shafer, a managing director for Grant Thornton's Healthcare and Life Sciences Industry division, said that the company's clients have similarly been concerned by regulatory questions surrounding Brexit. Grant Thornton is a tax, auditing, and advisory services company headquartered in Chicago.
"It looks like Brexit is going to happen, but we don't know the final terms of what that's going to look like yet," said Shafer. "People are concerned about what the final agreement's going to look like in terms of selling and distributing products into and out of the UK," he said. "Europe will stay Europe — that won't change much," he added, "but the UK becomes yet another country to deal with."
Waiting for guidance
When the European Commission enacted the IVDR in 2017, it also enacted the new MDR. Both regulations allowed a transition period, through May 2020 for the MDR and May 2022 for the IVDR. As the MDR's date for coming into force was more immediate, the Commission has focused more resources on preparing medical device manufacturers for achieving compliance.
For the European IVD industry, that has meant that there has been more focus to date on medical devices, although there is some overlap between the regulations. However, as the May 2020 deadline draws closer, some expect the commission to start issuing more detailed documents that specifically cover IVDs.
"We observed a clear focus by EU authorities on the MDR rather than the IVDR," said Oliver Bisazza, director of regulations and industrial policy at MedTech Europe, a Brussels-based European trade association that represents IVD and medical device manufacturers.
Bisazza noted that while the commission has issued some documents related to IVDR, these have actually been for both regulations. For instance, the commission issued guidelines covering cybersecurity and technical assessments under both the MDR and IVDR over the past two months. To date, the EU has not published any IVDR-specific guidance document, he said.
"This year should again be very important for implementing the IVDR," remarked Bisazza. "On May 26, the MDR will enter into full effect, and we expect that this will finally enable the EU authorities to devote more attention to the IVDR implementation than what has been observed between 2017 and 2019," he said.
Soon, the Commission is expected to publish a new guidance on the risk classification of IVDs under the IVDR. According to Bisazza, many stakeholders including MedTech Europe contributed to the guidance. This year, MedTech Europe also expects its members to submit their first IVD submissions to designated NBs. "This makes it essential to have good quality, EU-level guidance on the IVDR's risk classification rules," he underscored.
Another issue will be the deployment of regulatory infrastructure for what are considered high-risk IVDs, tests to combat infectious disease outbreaks and other public health-related challenges. Bisazza said it is imperative that the EU has the resources in place in the form of specifications, reference laboratories, and expert panels, to assess and clear such tests well in advance of the May 2022 deadline.
Finally, 2020 will be a "critical year" for the IVDR notified body system, Bisazza said. He noted that only about 10 organizations have applied for designation, versus the 21 that were designated under the IVDD, even though the IVDR places an even greater workload on NBs related to IVDs. MedTech Europe has previously voiced concerns about a potential lack of NB capacity in Europe related to the IVDR.
"2020 is therefore the year in which we must all as a community take honest stock of whether the EU notified body system for IVDs is on track to support the successful functioning of the IVDR," said Bisazza. "Any shortfall in notified body capacity would be extremely serious, as it would present risks to the continued availability of diagnostic tests upon which healthcare systems the world over relies," he said.
Grant Thornton's Shafer agreed that designating enough NBs to clear the anticipated number of IVDs submitted under the new regulation remains a "big challenge" for European regulators.
"I know they are working feverishly to achieve it, but I don't have any insight as to whether they will achieve it or not," he said. "They are starting to chip away and make some progress, but we'll see what happens."
Work to do
The burden isn't only on regulators to remake the regulatory landscape, both in the EU as well as in the UK following Brexit. Companies also have to do the work to prepare their submissions and to engage designated NBs to have their tests cleared on time so that they can ensure a smooth transition to the new regime, not just for themselves, but for their customers.
According to Erik Vollebregt, a founding partner at Amsterdam-based law firm Axon Lawyers, more than two years after the enactment of the IVDR and four years after the UK voted to leave the EU, test makers are still slow to keep up with developments.
"The IVD industry seems to remain generally not aware that the IVDR requires closing a huge gap in performance data and that it takes time to generate clinical performance data, as well as that most IVDs need a CE certificate under the IVDR, and that this takes time, as well," said Vollebregt, who specializes in EU legal and regulatory issues related to medical technology.
Also, given the shortfall in terms of NBs designated to evaluate tests under the IVDR, Vollebregt urged firms to see if the NB of their choice will be accredited, and if this designation will take place in time for the NB to provide a CE certificate under the IVDR.
"The current expectation," warned Vollebregt, "is that there will not be enough notified bodies for the certification demand on the market, so there will be scarcity of capacity and resulting collateral damage of companies that do not obtain their certificates according to their planning."
Given these issues, Vollebregt said IVD makers need to "massively engage" with NBs. Those who do not finalize their applications for IVDs that require certification, and have secured slots with NBs to have them cleared, will likely be late in obtaining clearance, and will have to make plans to manage a temporary absence on the market, he said.
"By the end of 2020, companies will be able to tell if they are on the right side of the line that separates companies that will make a successful transition to the IVDR regime and those that will not, resulting in market access disruptions and collapse of cash flow," said Vollebregt. He also encouraged companies to have transition plans in place for managing sales to the UK market once the UK leaves the EU.
"2020 will also be the year of the Brexit," said Vollebregt. "IVD companies need to have a Brexit scenario for their company and the consequences for CE marking of their IVDs."