NEW YORK – Delays, delays, and more delays, with more than a little uncertainty mixed in. Such was the nature of the European regulatory landscape over the course of the year 2022.
While the European Parliament decided early in the year to extend the grace periods for various classes of in vitro diagnostics that would have required a CE-IVD mark under the new In Vitro Diagnostic Regulation, the same issues that forced these extensions persisted throughout the year. A shortage of regulatory capacity continues to slow the implementation of the new regulation, while some resources necessary to fulfill the provisions of the regulation are also not ready.
While the IVDR does not directly apply to every country in Europe, its implications could be widespread throughout the continent, and at least one country, Switzerland, worried about the shifts in the IVDR and its deadlines, as well as the availability of certificate-holding healthcare products, voted last month to recognize diagnostics cleared by the US Food and Drug Administration.
Concurrently, the UK also decided to delay the end of the transition period for its own regulatory regime by a year.
Moreover, considering the ongoing challenges in implementing the IVDR's sister regulation, the Medical Device Regulation — the application of which was moved a year from May 2020 to May 2021 at the height of the COVID-19 pandemic, and faces new potential delays and amendments to its transitional regime — it's possible that the end of the transition period for some IVDs covered under the IVDR could be pushed ahead, too.
"For the IVDR, notified body capacity looks to be inadequate in the longer run, which would lead to a similar situation as under the MDR, where many IVDs would not be IVDR certified before the end of their grace period," remarked Erik Vollebregt, a life sciences and IP lawyer based in Amsterdam and one of the founding partners of Axon Lawyers, in an email this week.
Notified bodies are designated conformity assessment bodies that determine whether a company's products comply with the IVDR.
Vollebregt added, though, that IVDR applications have slowed because manufacturers perhaps wish to see if the grace periods will indeed be extended, as it appears may happen soon with the MDR.
"Notified bodies are actually advertising slots for IVDR because the stream of IVDR applications has dried up," said Vollebregt. "IVD companies have adopted a waiting game, while they really should be applying now because at this moment there is capacity," he added.
Deadlines in motion
Both the MDR and IVDR were enacted in 2017, replacing older directives that had been in force since the 1990s, including 1990's Active Implantable Medical Devices Directive (AIMDD) and 1993's Medical Devices Directive (MDD). While 1998's IVD Directive (IVDD) had allowed many IVDs to obtain a CE-marking via a self-certification process, the new regulation requires most IVDs to be assessed by the notified bodies (NBs) before they can be marketed.
Initially, manufacturers of medical devices and IVDs had until May 26, 2020, and May 26, 2022, respectively, to obtain new certificates for their products from a designated NB. By those dates, both regulations would begin to apply. However, given the larger administrative burden of the new regulations, plus a shortage in capacity to handle those applications, the EU decided to push the application date of the MDR back a year to May 2021. The ongoing COVID-19 pandemic in part influenced that decision, as travel restrictions made in-person audits of NBs difficult.
The EU did not change the ultimate date by which products holding certificates under the AIMDD and MDD would require new ones under the MDR, May 26, 2024. However, earlier this month, the European Commission proposed to possibly extend that deadline again, citing ongoing shortages in regulatory capacity, plus the threat that Europe will be faced with a shortage of compliant medical devices.
The Commission has, therefore, stated that it is contemplating a legislative proposal to be published in January 2023 delaying the deadline for obtaining new certificates under the MDR to May 2027 for certain classes of higher-risk devices, and to May 2028 for classes of lower-risk devices.
The reason for delaying the deadline is that while 36 NBs have been designated to date to assess medical devices under the MDR, stakeholders believe there is still not enough capacity in those NBs to assess all the devices holding certificates by May 26, 2024. A proposal for an amendment of the MDR will likely be undertaken by the Commission in January.
While the proposed extensions to the MDR transition periods do not directly impact IVDs, the fact that the Commission is making the amendments does not bode well for implementing the IVDR, as just seven NBs have been designated so far to evaluate IVDs under the new regulation.
Those designated include 3EC International in Slovakia, Dekra Certification's locations in Germany and the Netherlands, BSI in the Netherlands, France's GMED SAD, and Germany's TÜV Rheinland LGA and TÜV SÜD.
Earlier this year, the EU decided that it would not extend the date of application of the IVDR, as it had with the MDR, but that instead it would extend the date of application for legacy tests in a staggered way, depending on the device risk class, with all IVDs expected to be compliant by 2028.
As most molecular devices fall into Class C under the IVDR, those that held a CE-IVD mark obtained under the IVDD, or prior to May 26, 2022, currently require clearance by May 2026.
It is worth noting that currently that situation is unchanged though that small number of designated NBs is tasked with reviewing all the molecular tests in the EU in four years' time (whereas 21 NBs had been designated under the IVDD). In October, the EU's Medical Device Coordination Group (MDCG), which oversees issues related to the medical sector, together with stakeholders, published a survey of NBs. In it, they reported that 40 percent of IVDR-designated IVD clients were EU-based, while 60 percent were based outside the EU. According to the survey, it takes on average, between a year and 18 months to have one's quality management system and product certified under the IVDR for the majority of submissions.
Despite these ongoing bottlenecks, the EU has been churning out guidelines to support its transition to the new regulatory regime and some resources have been coming online, albeit behind schedule. In May, for example, the MDCG issued a guidance about the verification of Class D devices, the highest-risk category, under the IVDR.
In October, a draft guidance appeared on the roles of authorized representatives. Under both the MDR and IVDR, non-EU companies require an authorized representative within the EU to support the placement of their products on the EU market. And this month, the EU published an information pack to support the development of European Reference Laboratories (EURLs), which will play a role under the terms of the IVDR by verifying the claims of test manufacturers by assessing the performance of their diagnostics.
According to the information pack, candidate labs were supposed to be preparing the documents for assessment in early 2023, with a planned designation by the Commission by summer 2023.
Parts of the Eudamed database, which is also central to the implementation of the IVDR, are also up and running, though it has still not been audited for full functionality and has not become mandatory to use. However, some EU member states have started to require the use of the modules of Eudamed that are available for use on a voluntary basis. Under the IVDR, test makers are expected to upload data about their products to Eudamed, including conformity assessments by notified bodies, performance study data, and post-market surveillance information.
Richard Houlihan, CEO of EirMed, a company that helps others manage their Eudamed submissions, said that while entering one's data into the database will remain voluntary through the end of 2024, when it will become mandatory, the company has submitted data on thousands of devices for clients this year.
Houlihan added in an email that the proposed changes to the MDR transition dates have had a "surprising effect" as more companies have been looking to upload data on devices holding certificates obtained under the MDD as of late. "We are waiting to see if more changes will come for the IVDR deadlines," Houlihan said.
Some features remain offline for the time being, including those related to vigilance, market surveillance, and clinical investigations. "Overall, Eudamed is stable," Houlihan said. "While Eudamed will not be fully functional until Q4 2024, our advice remains to get your data in now and avoid a headache later with a pressured project," he said.
Meanwhile, in a sign of the impact of the IVDR throughout Europe, not just in the EU, Switzerland recently updated its own regulation of diagnostics, at least in part, as a result of the changing IVDR landscape.
The Swiss have had other issues to manage related to the expiration of Switzerland's mutual recognition agreement with the EU regarding the IVDD, as well as the Swiss government's refusal to ratify the broad internal market access instrument, called the Institutional Framework Agreement, or IFA. The latter was negotiated between Switzerland and the EU from 2014 to 2019 and included the IVDR, which resulted in non-applicability of the IVDR in Switzerland.
At the end of November, the Swiss Federal Assembly, the Alpine country's federal legislature, voted to accept medical devices with US FDA authorization on its market, in part to stave off potential shortages resulting from regulatory bottlenecks in the EU. The decision still needs to be incorporated in Swiss law.
Previously, Switzerland had only accepted devices holding a CE-IVD on its market. Swiss Medtech, an association that represents the country's medical technology industry, in a statement explicitly linked the decision to ongoing delays in the implementation of the MDR and IVDR.
Peter Biedermann, managing director of Swiss Medtech, said in a Nov. 28 statement that the move was "a response to circumstances that could no longer be ignored," citing "problems with the implementation of the new European [MDR] and the negative consequences concerning availability, product range, and quality of medical devices throughout Europe."
As innovations are increasingly being introduced first to the market in the US, Biedermann noted, new products will reach Europe "with a delay, at best."
Switzerland is neither an EU member nor a signatory to the European Economic Area (EEA) Agreement, unlike other non-EU members Iceland, Liechtenstein, and Norway. It does have a mutual recognition agreement with the EU. However, in May 2021, at the time the MDR came into force, the EU decided that the MRA no longer applied to Swiss medtech products, as Switzerland had not signed the institutional agreement. Switzerland in response passed an ordinance requiring registration to sell non-Swiss medtech products domestically.
Anita Holler, a spokesperson for Swiss Medtech, said in an email that mutual trade barriers have existed between the EU and Switzerland since that time. Switzerland is now considered a third country in regard to the EU, and local manufacturers need an authorized representative in the EU and a CE-IVD mark to sell their products outside of Switzerland. EU manufacturers in turn now require the same to sell their products inside Switzerland. According to Holler, when the Swiss Federal Council broke off negotiations with the EU regarding the institutional agreement related to the MDR, the chance of a resolution of the issue receded into the distance.
With regards to the Federal Assembly vote to accept FDA-cleared products on the Swiss market, Holler said that the Swiss Federal Council now must implement the parliamentary order within two years.
The UK – still at a standstill
While delays continue to plague the transition to the MDR and IVDR within the EU, the UK has faced delays of its own this year. When the island country left the EU in February 2020, it did so with no agreement with the union on mutual recognition of medical devices and IVDs.
A year later, the British parliament passed the Medicines and Medical Devices Act of 2021, which enabled the creation of a new regulatory framework in the UK. Later in 2021, the UK Medicines and Healthcare Products Regulatory Agency opened a public consultation on a new regulatory system that largely mirrored the IVDR. Under the proposed regulation, UK companies and foreign companies seeking to sell molecular tests into the UK would need to obtain a certification mark, called the UK Conformity Assessed or UKCA mark, from an approved standards organization, called an approved body, that has been designated to assess IVDs.
Under its initial proposal, MHRA said that companies could continue to sell IVDs holding a CE-IVD mark obtained under either the IVDD or IVDR until July 2023, by which time they were expected to obtain a UKCA mark. The condition applied only to products placed on the island of Britain with its nations of England, Scotland, and Wales, while Northern Ireland continues to operate under a hybrid regime where both the CE-IVD and UKCA marks are recognized.
On Oct. 21 though, MHRA decided to delay what it calls the "standstill period" by a year to July 2024. According to Stephen Lee, director of diagnostics regulation at the Association of British HealthTech Industries, the delay still requires legislative approval, which may come early in 2023.
Lee noted that ABHI is working with MHRA and the UK's Office for Life Sciences to cooperate on international recognition for UK-cleared IVDs, routes for innovation, and system capacity. Initial proposals in these priority areas will be published in February 2023, Lee said.