Managing the challenges of the new IVDR: Lessons from the pandemic

This article details how regulatory intelligence can help medtech companies assess the impact of the new EU legislative framework for in vitro diagnostics (IVDs). Using the example of COVID-19 antigen tests, the author looks at how regulatory intelligence helped device manufacturers manage the changes in regulations during the pandemic and how the lessons learned can support the industry in assessing and planning for the impact of the new legislative framework for IVDs that will come into place in May 2022.

Keywords – Class D, COVID antigen tests, IVDR, medtech
 

Introduction

The implementation of Regulation 2017/746 on in vitro diagnostic devices (IVDR) in May 2022 has proven challenging. There has been progress with the publication of the first draft implementing regulations for common specifications and transitional arrangements for the IVDR, as laid out in Regulation (EU) 2022/112.¹ However, medtech companies have long been aware that the complexity of the IVDR and the exceptional circumstances arising from the COVID-19 pandemic have made it highly unlikely that EU member states, health institutions, notified bodies, economic operators, and other relevant parties would be able to ensure the proper implementation and full application of the regulation despite the recent extension of certification timelines beyond the stipulated May 2022 date of application.² The extended transition periods are until May 2025 for high-risk devices (Class D); May 2026 for Class C devices; and May 2027 for lower-risk devices (Class B and A sterile).
 
The Medical Device Coordination Group advises the European Commission (EC) and EU member states on harmonized implementation pathways for medical device regulations. In February 2022, the group published a joint implementation plan in which it outlined the progress toward full functionality of the European Database on Medical Devices, EUDAMED.³ The implementation plan helps companies prepare for the upcoming May implementation, allocate resources, and prioritize operations. The priorities are split into two sets:
 

• Set A – Setting the minimum requirements for devices to have access to the market (those related to the framework for contingency planning and availability of notified bodies).

• Set B – Including nonmandatory legislation and guidelines that, while not obligatory, would greatly benefit the work of all interested parties. A list of EU reference laboratories is included.

 
The EC is also working on establishing the EU reference laboratories network and adopting common specifications for 16 IVD types. These reference laboratories will carry out batch-release testing for Class D (high-risk) devices. However, it is possible to place devices on the market without the batch release after assessment by the notified body and, in some cases, by an expert panel. For some less-common Class D devices, there could be no EU reference laboratory because there are no candidates.
 
In addition, considering that the completion of the conformity assessment under the IVDR is expected to take between 9 and 12 months, the delay in implementation of the regulation for high-risk IVDs will also likely help avoid disruption in the availability of such devices.
 

Regulatory framework for COVID-19 self-tests

There have been many changes in the regulatory landscape during the pandemic, including exceptional import and notification procedures for medical devices, as well as interim orders and policies to expedite product approval and avoid product shortages that could put public health at risk.
 
COVID tests were key for enabling the diagnosis, screening, contact tracing, and isolation of people infected during the pandemic. There are different requirements for tests for professional use, intended for use by healthcare professionals, and for self-tests, which are devices intended for use in the home environment. It is still necessary to ensure there is an uninterrupted supply of self-tests for COVID-19, and regulations in Europe are aimed at granting access to tests for all citizens.⁴
 
Competent authorities increased the number of published regulations relating to these IVDs to ensure the regulatory framework was dynamic and able to accommodate the growing demand for tests and the recall of underperforming tests. This resulted in unprecedented times for regulatory professionals and has highlighted the need for them to constantly monitor the regulatory landscape. These expanded regulatory intelligence tasks are critical before taking any actions.
 
Laboratory-based tests for COVID-19 and point-of-care/near-patient tests (professional-use tests) are classified as IVDs under the In Vitro-Diagnostic Medical Devices Directive (IVDD) 98/79/EC to allow manufacturers to place COVID-19 tests on the market without further explicit authorization, provided they declare the device in compliance with the legislation and affix the CE [conformité Européenne] mark on the product themselves. The CE mark indicates a product has met European safety, health, and environmental protection requirements.
 
According to the IVDD 98/79/EC, IVDs are divided according to four categories: List A, List B, Self-test, and General and have different requirements depending on this rule-based classification. This meant that only IVDs mentioned in two extensive lists were classified in the top two risk classes (A and B). COVID-19 tests can be classified under the two different categories, professional use tests and self-tests, depending on their intended purpose.
 
For COVID-19 devices intended for professional use, the manufacturer should prepare an EC declaration of conformity. The manufacturer may then affix the CE mark to the device and place it on the market. This procedure is frequently referred to as self-certification. These self-certifiable products represent about 80% of all IVDs on the EU market.
 
However, self-tests and high-risk devices listed in Annex II of IVDD 98/79/EC must undergo certification by a notified body to ensure the device design and information provided for its use are suitable for nonprofessional users.
 
The absence of premarket regulatory checks and common technical specifications for COVID-19 tests, under the existing IVDD was a challenge, as was the shortage of notified bodies to carry out audits and certifications of tests.
 
As these products are crucial for the early diagnosis of COVID-19, the EU worked to guarantee its supply. Following a Health Security Committee agreement on a common list of COVID-19 rapid antigen tests, the EU member states agreed to mutually recognize results for a selection of tests and a common standardized set of technical specifications and data, to be included in COVID-19 test result certificates.
 
This information is continuously reviewed and updated and is available on the EC’s COVID-19 in vitro diagnostic devices and test methods database.⁵ Manufacturers and distributors are therefore required to perform continuous regulatory intelligence work to stay current with regulations at a European and national level. The volume of local regulatory documents published has increased notably during the pandemic and therefore, the time required for data collection, compilation, and assessment has reached the limit for many regulatory departments.
 
It has been important for companies operating in the import/export areas to get a complete view of regulations for importing COVID-19 supplies. Having dedicated regulatory intelligence resources for monitoring worldwide requirements is key to navigating the special emergency procedures established, for COVID-19 tests, as well as respirators, face masks, and other medical devices.
 
It is also important to monitor and analyze documents related to packaging or relabeling, 3-D printing devices, and in-house IVDs, especially since the pandemic. (The shortage of resources, including staff and products, has triggered an increase in the use of some in-house and 3-D printing devices in hospitals).
 
Authorization under exceptional circumstances has opened the possibility for many companies to develop and expand their market strategies in new regions. Medtech companies are also interested in additional information, such as competitive analysis, past product precedents, and postmarketing information about competitor products. By performing this analysis, regulatory intelligence can provide key insights from precedent and lessons learned from the pandemic, which can be essential in reducing a product’s time to market.
 

Managing the challenges of the new IVDR

The IVDR replaces the IVDD’s four categories with a risk-based classification system. Under the IVDR, IVDs can be classified as Class A (low risk), B, C, or D (high risk). IVDs with existing valid notified body-issued CE certificates – List A, List B, and Self-test IVDs used by laypersons in the home environment – may continue to sell those devices until May 2024 or until the certificate expires and provided there are no significant changes to the design and intended purpose. The requirements for self-test IVD devices have become stricter under the IVDR and they will generally be classified in the highest-risk class.
 
This means that many self-test IVDs will become Class D devices under IVDR and require certification to be audited and certified by a notified body for the first time by May 2022. This will significantly change the regulatory landscape because they will undergo a conformity assessment based on the quality management system but will be assessed individually. Besides, these Class D devices, along with companion diagnostics, devices for self-testing, and devices for near-patient testing will be assessed individually, rather than by representative group (see Table).
 



Based on a recent medtech Europe Survey Report,⁶ in the “worst-case” scenario, only 24% of IVDs currently on the market would be available CE-marked under the new IVDR requirements should the regulation be implemented in May 2022. Many of these devices would be the lowest-risk, Class A, which cannot be used alone and instead must be used with higher-class B, C, and D reagents.⁶ Also, many manufacturers still do not have contractual agreements with notified bodies to assess and certify their quality management systems and IVDs as required by the new IVDR.

EU reference laboratories and expert panels play an important role in IVD conformity assessments. There is a great increase in the number of tests requiring notified body certificates under the IVD Regulation along with the upload of specific information to the EUDAMED database.
 
As set out in IVDR Article 78, the role of the reference laboratories is to verify the claimed performance of Class D devices under the applicable common specifications and carry out testing on samples. For novel devices that do not have any existing common specifications, expert panel review is also required as an additional procedure.
 
This is one example of the implications of working with a new regulatory system that is still being built. Medtech companies are also facing challenges with the availability of notified bodies and how the regulation is interpreted.
 

Conclusion

Regulatory intelligence helps medical device developers and manufacturers manage the ongoing changes in IVDR as well as save time navigating requirements across regions. Performing a regulatory intelligence analysis prior to the technical file scoping and preparation, specifically on the performance evaluation, is crucial to accelerating the pace of obtaining a CE mark. For IVDs, which are of critical importance to healthcare systems, like IVD COVID-19 tests, completing the IVDR certification before the deadline is a priority.
 
Proactively identifying regulatory changes and assessing their impact on business has always been the main role of regulatory intelligence, but the COVID pandemic has shown medtech companies the real value of having a structured process to identify and track multiple complex regulatory changes, allowing them to stand out in these difficult times by showing foresight and agility. This ability to anticipate, prepare, and rapidly respond in a challenging environment will be crucial for the industry as its faces future challenges and health threats.
 
Abbreviations
CE, conformité Européenne ; EC, European Commission; EU, European Union; EUDAMED, European Database on Medical Devices; IVD, in vitro diagnostic ; IVDD, In Vitro-Diagnostic Medical Devices Directive; IVDR, In Vitro Diagnostic Medical Devices Regulation.
 
About the author
Raquel Carnero Gómez, PhD, is senior medical device specialist at IQVIA Regulatory Intelligence. She has more than 15 years’ experience in regulatory affairs in both pharma and medical device companies. Carnero Gómez has a doctorate degree in pharmacy from the University of Salamanca, Spain, a master’s degree pharmaceutical industry and pharmacoeconomics, and a diploma in public health. She can be reached at raquel.carnero@iqvia.com

Citation Carnero Gómez R. Managing the challenges of the new IVDR: Lessons from the pandemic. Regulatory Focus. Published online 19 April 2022. https://bit.ly/3vs0OSZ

References

All references were accessed and/or verified on 15 March 2022.

1. European Union. Regulation (EU) 2022/112 … amending Regulation (EU) 2017/746 as regards transitional provisions for certain in vitro diagnostic medical devices and the deferred application of conditions for in-house devices. Dated 25 January 2022. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32022R0112&from=EN
2. European Commission. Questions and answers on the progressive roll-out of the new In Vitro Diagnostic Medical Devices Regulation. Dated 14 October 2021. Q&A: New In Vitro Diagnostic Medical Devices Regulation (europa.eu)
3. Medical Device Coordination Group. European Commission website. Joint implementation and preparedness plan for Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR). Dated March 2022. https://ec.europa.eu/health/system/files/2022-04/md_joint-impl-plan_en.pdf
4. European Commission. COVID-19 tests: Questions and answers on in vitro diagnostic medical device conformity assessment and performance in the context of COVID-19. February 2021. https://ec.europa.eu/health/system/files/2021-06/covid-19_ivd-qa_en_0.pdf
5. European Commission. COVID-19 in vitro diagnostic devices and test methods database. No date. https://covid-19-diagnostics.jrc.ec.europa.eu/
6. Medtech Europe website. Survey report – Analyzing the availability of in vitro diagnostic medical devices (IVDs) in May 2022 when the new EU IVD regulation applies. Posted 8 September 2021. https://www.medtecheurope.org/resource-library/medtech-europe-survey-report-analysing-the-availability-of-in-vitro-diagnostic-medical-devices-ivds-in-may-2022-when-the-new-eu-ivd-regulation-applies/