In-Vitro Diagnostic Regulation

The new European Union (EU) in-vitro diagnostic regulation (IVDR) introduces substantial changes in the regulatory framework for in-vitro diagnostic medical devices (1), replacing the current in-vitro diagnostic medical devices directive (IVDD) (2). For most diagnostic manufacturers, procedures for conformity assessment will become more complicated as companies transition away from self-certification and towards independent conformity assessment by Notified Bodies (NBs). Under the EU IVDR, companion diagnostics will fall under Class C and will therefore undergo a high level of scrutiny from NBs as well as tighter clinical requirements, particularly for pharmaceutical companies developing their own companion diagnostics.

Key differences between IVDR and IVDD

One of the main changes in the IVDR is to increase the involvement of NBs. Under the current IVDD, less than 10% of high-risk devices are subject scrutiny by to NBs whereas under the new IVDR around 80% will be under their control (3). In addition, the IVDR introduces a new set of rules for ‘in-house’ devices including justification for the use of a device and requires diagnostic manufacturers to implement appropriate quality management systems to ensure their safety and performance of their devices (3).

On 24 Jan. 2022, the European NBs published a position paper identifying the key challenges in terms of ensuring adequate certification support IVDR and the new medical devices regulation (MDR) (4). The shortage of NBs with appropriate designation to the new IVDR (and MDR) has been a cause for concern; only six NBs had been designated to the IVDR, as of December 2021 (4). European NBs called for the regulators to extend the transition period for IVDR beyond May 2024 and for closer alignment between NBs and competent authorities regarding authorizing remote audits (3).

In December 2021, the European Parliament and the Council sanctioned the progressive roll out of IVDR from 26 May 2022 (5). This action will change the dates of application of some medical devices. For instance, the new requirements will apply from May 2025 for class D higher risk devices; whereas for devices of the lower risk class C (which include companion diagnostics), the date of application will be extended until May 2026, and applications for lower risk class devices (class B and A sterile) will start in May 2027 (5).

European database on medical devices

The European database on medical devices (EUDAMED) has been created to increase transparency and integrate different electronic systems to collate and process information about medical devices and related companies (manufacturers) (6). EUDAMED will be populated by the data owners, who are responsible for the quality of data, and part of EUDAMED will be accessible to the public (7).

EUDAMED is composed of six modules related to: actor registration, unique device identification (UDI) and device registration, NBs and certificates, clinical investigations and performance studies, vigilance and post-market surveillance, and market surveillance. The actor registration module became active 1 Dec. 2020 and enables economic operators to submit, by means of an actor registration request, the information necessary to obtain a single registration number (SRN) (8). The SRN allows economic actors to be clearly identified throughout the EU and is required by a NB when submitting an application for conformity assessment. Each actor needs to appoint at least one Local User Administrator (LUA) to verify, manage mandates, link (depending on actor role), and manage users and user access requests.

Modules two and three, the UDI/device registration and NBs and certificates, became active in October 2021. The second module introduces an EU device identification system based on a UDI linking the device to the applicable certificates to help improve traceability (9). The third module enables NBs to register information in EUDAMED regarding Conformitè Europëenne (CE) Mark certificates issued (including amendments and supplements), suspended, reinstated, withdrawn, or refused, and other restrictions imposed on these certificates; all information will be accessible to the public and help to improve transparency of the process (10).

Critical documents for the three remaining modules—clinical investigations and performance studies; vigilance and post-market surveillance; and market surveillance—will launch when the EUDAMED database becomes fully operational in May 2022. Industry experts anticipate that analytical and clinical performance data will come under greater scrutiny under the new IVDR and the performance evaluation report (PER) will require continuing updates. In addition, manufacturers are likely to face more stringent post-market surveillance requirements and may need to conduct post-market performance follow-up (PMPF) and provide period safety update reports (PSUR) for Class C and D devices (11).

The three remaining modules will provide clinical investigations or performance studies with a single identification number (SIN) and incident reports will automatically be assigned a reference number (the responsible competent authority will add its own additional case number). In addition, a field safety corrective action (FSCA) will automatically be assigned a reference number (the responsible competent authority will add its own case number). All these identifiers will help in the unequivocal identification of key case information, and the EUDAMED database will facilitate coordination and cooperation between member states (7).

Get ready … what is your regulatory compliance strategy?

The lack of official documentation for all six modules has made it challenging for companies to prepare for EUDAMED compliance. Therefore, it is essential for medical device manufacturers to establish a regulatory compliance strategy (Table I) (12) and put in place a leadership team to ensure the smooth transition to the new IVDR—failure to do so is likely to be met with lengthy product delays (13).

Table I. Company checklist for regulatory compliance strategy for the new in-vitro diagnostic regulation (IVDR).

To this end, IVD manufacturers should have assigned budgets and staff to ensure their organization is fully prepared once EURAMED goes live at the end of May 2022. Staff will need to be trained to make sure data for all devices are entered into the EU database in a way that allows for extraction of EUDAMED-specific data, and procedures should be in place to ensure that data uploads or downloads are performed correctly and consistently (5). Manufacturers should also be ready to approach the competent authority to request an SRN, and at least one LUA should be appointed and other users authorized to enable staff to execute specific activities such as entering, reviewing, and uploading information in a timely manner (5).

Failure to adjust to these regulatory changes may result in penalties and loss of market access; however, the implementation of a good regulatory compliance strategy can help to mitigate these risks. While it may take time for manufacturers to navigate the new IVD regulations, it is hoped that the framework that has been put in place will provide them with a more efficient, transparent, and consistent pathway for the regulatory approval of IVDs.

References

1. EU, Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on In Vitro Diagnostic Medical Devices and Repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance), Legal Document, eur-lex.europa.eu (April 2017).
2. EU, Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on In Vitro Diagnostic Medical Devices, Guidance Document, eur-lex.europa.eu (December 1998).
3. EC, “Public health: Commission Proposes a Progressive Roll-out of the New In Vitro Diagnostic Medical Devices Regulation,” Press Release, 14 Oct. 2021.
4. Emergo, “European Notified Bodies Issue Updates on MDR, IVDR Implementation Challenges,” Blog, 24 Jan. 2022.
5. EU, Proposal for a Regulation of the European Parliament and of the Councill amending Regulation (EU) 2017/746 as Regards Transitional Provisions for Certain In Vitro Diagnostic Medical Devices and Deferred Application of Requirements for In-House Devices COM/2021/627 Final, Legal Document, eur-lex.europa.eu (October 2021).
6. EC, EUDAMED database available from ec.europa.eu [Accessed 20 April 2022].
7. R. Boumans, “Understanding the New Eudamed: The Role of Eudamed in MDR and IVDR Compliance,” Emergo, White Paper (August 2018).
8. S. Broussard, “EUDAMED3 Update: Two More Eudamed Modules Will Be Available Later This Year & Guidance on Alternatives Until the Remaining Three Modules are Released and the Database is Fully Functional,” Criterion Edge, Article, 3 May 2021.
9. EC, UDI/Devices registration available from ec.europa.eu [Accessed 20 April 2022].
10. EC, Notified Bodies and Certificates module available from ec.europa.eu [Accessed 20 April 2022].
11. E. Loh and R. Boumans, “Understanding Europe’s New Medical Device Regulation—MDR 2017/745,” Emergo, White Paper (July 2018).
12. Emergo, European IVDR Readiness Checklist, available from emergobyul.com [Accessed 20 April 2022].
13. Operon Strategist, “Is Regulatory Compliance Strategy for Medical Devices Effective?” prfire, Press Release, 15 May 2020.

About the author

Cheryl Barton is director of PharmaVision, info@pharmavision.co.uk

Article details

Pharmaceutical Technology Europe
Vol. 34, No. 5
May 2022
Pages: 7–8

Citation

When referring to this article, please cite it as C. Barton, “In-Vitro Diagnostic Regulation,” Pharmaceutical Technology Europe 34 (5) 2022.