NEW YORK – The European Commission is considering a proposal that would see the implementation of its In Vitro Diagnostic Regulation phased in over the next few years, rather than enforcing the regulation from its official application date of May 26, 2022, for most IVDs.
The Commission had been under pressure in recent months from various stakeholders, who feared that challenges in implementing the regulation might cause tens of thousands of diagnostics to lose clinical compliance overnight, disallowing their use, and endangering the quality of EU healthcare.
While industry observers welcomed the new proposal, they cautioned that many of the challenges related to implementation of the IVDR remain, regardless of its enforcement date.
"Upon initial review, the proposed EU amendment to delay implementation of IVDR appears to be a victory for the various stakeholder groups that have been lobbying the EU over the last two years, seeking a delay, and/or a phased introduction into full force of the regulation," noted Dave Smart, director of the scientific operations team at Diaceutics, a UK biotechnology company that has been calling for a phased implementation for the IVDR. "However, the devil is in the details and the proposed amendment still contains some causes for concern," Smart said.
Europe has been in the midst of a regulatory overhaul for the past four years, and two pieces of legislation, the Medical Devices Regulation, or MDR, and the IVDR form the cornerstones of an effort to remake the way health authorities evaluate the safety of tests and devices on the market.
For makers of IVDs, the new IVDR, which replaces 1998's IVD Directive, completely rewrites the rules for making and selling IVDs. Under the 23-year-old IVDD, only about 8 percent of tests required assessment by a designated conformity assessment body, called a notified body, or NB, meaning most IVDs obtained CE-IVD marks via a self-certification process.
Under the IVDR, around 85 percent of tests will require assessment via an NB. The IVDR also impacts laboratories that use laboratory-developed tests, or modified commercial tests, in their services, by mandating that they adopt CE-IVD marked tests for particular indications or provide a rationale for using laboratory-developed tests, referred to in the IVDR as in-house devices.
Yet to date, just half a dozen NBs have been certified to assess all of Europe's IVDs, which number in the tens of thousands. That backlog also impacts labs, which are being instructed to adopt tests that could potentially soon lose compliance. And with the May 2022 application deadline looming, and under pressure from stakeholders, the EC decided to propose a phased implementation, so that IVDs can remain in use where needed, while the transition continues. The Commission noted the lack of NBs as one of the reasons for proposing a phased implementation, but in a statement also blamed the ongoing COVID-19 pandemic for delays.
"Due to COVID-19 travel restrictions, notified bodies were not able to carry out the required on-site audits at manufacturers' premises to verify the manufacturing and other relevant processes," the Commission noted in its statement. It also said that such restrictions "still significantly hamper the proper conduct of conformity assessment by notified bodies."
The Commission in April 2020 delayed the year of application of the MDR by one year, citing the COVID-19 pandemic as a cause. To resolve issues with the IVDR, it has made a different kind of proposal, retaining the year of application, but introducing staggered legacy devices grace periods for IVDs, depending on the device class.
For IVDs that already hold a CE-IVD mark from an NB, roughly 8 percent of the tests of the market, those certificates will remain valid until May 2025, a year later than originally scheduled. The Commission said it made this adjustment because certificates for medical devices obtained under the previous directive remain valid until 2024, and the addition of a year for IVDs will prevent a regulatory bottleneck as certificates for both medical devices and IVDs would have expired at the same time.
For devices that did not require a certificate from an NB under the IVDD, which comprises the majority of IVDs on the market in Europe today, and would have needed to obtain a CE-IVD mark prior to the May 26, 2022, application date, those certificates will remain valid until May 26, 2025, for class D devices, the highest risk class, which includes a variety of tests, such as those for determining viral load and blood-borne diseases.
For medium-risk Class C devices, the same situation will apply, except that the certificates will be valid until May 26, 2026. Most molecular tests fall into Class C, which covers genetic tests, companion diagnostics, infectious disease diagnostics, and assays for stratifying cancer patients.
Certified Class B and sterile Class A devices will remain compliant until May 26, 2027, according to the proposal. Class B covers all other devices not covered by Class D and Class C, such as at-home pregnancy tests, and Class A, in general, covers laboratory equipment, such as reagents and instruments.
For in-house devices, the proposal moves the date of implementation of most parts of the IVDR to May 26, 2024. This may benefit labs in that the IVDR mandated that they maintain dossiers for their tests, including information about their manufacture and use, as well as performance data, activities the Commission acknowledged were slowed by the pandemic, adding its proposal would "give health institutions extra time to comply with the new requirements."
With regards to the provision that labs justify their use of an in-house device instead of a commercial, CE-IVD marked test, the Commission proposes a deferment until May 26, 2028, as "health institutions will need an overview of CE-marked in vitro diagnostic medical devices available on the market to comply with this requirement."
Still, some provisions affecting laboratories will still take effect next May, and the Commission noted in a Q&A that the application date of the IVDR will remain May 26, 2022, meaning that all new IVDs must achieve a CE-IVD from a designated IVD under the new regulation starting that date.
Industry observers in general welcomed the Commission's proposal but noted that it does not in itself address some of the issues that caused the IVDR to require a phased implementation in the first place.
Erik Vollebregt, a life sciences and IP lawyer and founding partner of the Amsterdam-based life sciences law firm Axon Lawyers, noted that the proposal is not a "one size fits all delay," as the date of application for the IVDR does not change. He said that the strategy behind the proposal is similar to the one the Commission created for the MDR, where more legacy devices were phased into regulation over time.
Rather than merely moving the date of application, the proposal for the IVDR instead creates staggered grace periods, noted Vollebregt. It remains to be seen if "this is sufficient for enough notified body capacity to come online timely, and for the still few notified bodies to be able to spread the workload in a way that all devices can be assessed under the IVDR in time."
Vollebregt also added that while the proposal delays certain obligations for in-house devices, labs will still have to have technical documentation for their tests as of May 26, 2022, and cannot transfer those tests to a legal entity, nor produce them at industrial scale. In that regard, labs still have "lots of homework" to do related to being compliant with the IVDR, he remarked.
Diaceutics' Smart similarly pointed out that the proposal did not provide a mechanism for increasing NB capacity. "While this move will help defer the potentially catastrophic withdrawal of up to 76 percent of IVDs from the market, it does not resolve the fundamental problem of too many devices requiring conformity assessment and still much too few NBs to execute the work," said Smart.
Smart noted that in addition to the six designated NBs, another 11 have expressed interest in becoming designated to assess conformity of tests with the IVDR. Yet this number will still be less than the total number of NBs that were designated under the IVDD and will be expected to handle a 700 percent increase in workload, be it by 2022 or 2025. That workload will also make it more difficult to get new tests through the assessment process, "stifling innovation and improvement of IVDs in the EU," Smart said.
In all, Smart called the proposal "welcome and timely" in that it would remove immediate pressure on manufacturers, but said it "does not address the root cause of the problem," such as a lack of NB capacity or compliance training for laboratories. He stressed that labs need to be aware that the proposal only delays some parts of the IVDR that affect them, but not all of them.
"No stakeholder can assume that the proposed delay is a complete solution to the problem and will need to ensure they maintain their efforts to become compliant to the regulation as soon as possible," said Smart.
The Commission's proposal, as of now, remains just a proposal. It will still have to navigate the EU's legislative process, which could take months. MedTech Europe, a trade association representing most European IVD and medical device manufacturers, has been calling for a delay to the IVDR since the start of the pandemic.
The association posted in response to the proposal that it is important that the Commission "seeks to safeguard the availability of in vitro diagnostic tests to patients and healthcare systems, particularly in a challenging pandemic situation, while transitioning into the regulation," and that MedTech Europe and its members "remain fully committed to the goals" of the IVDR.
The association added that, "All parties will now have to assess if the suggested amendments address the critical implementation challenges at stake for an efficient and successful transition."