The EU IVDR Regulation – An Overview – Part I
The PIP breast implant scandal brought to light weaknesses in the overall regulatory process for control of IVDs including, but not limited to, the system of certification by Notified Bodies (NBs), the need for risk-based classification and more clinical evidence through the device lifecycle. Thus, in order to better align with international guidelines, the European Union’s In Vitro Diagnostic Regulation (IVDR) 2017/746), which replaces the current In Vitro Diagnostic Directive (IVDD 98/79/EC), will fully apply from May 2022. Since at present a majority of IVDs are self-certified, the IVD industry will feel a marked change once the risk-based classification system is introduced and greater NB oversight is enforced.
In contrast to the EU MDR, the scope of the IVDR includes diagnostic and monitoring devices that may attach to a person, but are specifically used for monitoring human functions. IVDs span from a blood collection tube or a pregnancy test, glucose & cholesterol tests, to a multipurpose analyzer intended for hospital laboratories. It is interesting to note that while the IVDR affects a smaller product range, it has a longer implementation period.
Some of the major changes to be considered in the EU IVDR are increased regulatory oversight, expanded clinical evidence requirements, greater requirements for IVD manufacturers and intensified supervision of Notified Bodies.
What’s new in EU IVDR?
Risk-based classification with greater NB oversight
The IVDR identifies four risk classes: Class A (lowest risk), Class B, Class C, and Class D (highest risk) wherein for devices with multiple intended purposes, all purposes must be classified, and the highest risk class is applicable. Class B, C, and D IVDs will require NB intervention as a part of their conformity assessment, adding to the burden on NBs, who already had extra work due to the MDR. Interestingly, it is the manufacturer who is responsible for classifying a device; not the Notified Body or Competent Authority. In accordance with Article 47 if a manufacturer and Notified Body cannot agree on the classification, the Competent Authority will make the final determination.
Unlike the IVDD, the IVDR encourages a shift from the pre-approval stage (i.e., the path to CE Marking) to a life-cycle approach, similar to the life-cycle view advocated by the US Food and Drug Administration and many international standards. The incorporation of European guidance (MEDDEVs) into the regulation, some concepts that were not previously applicable to IVDs, demonstrate the life-cycle approach namely: Borderline and Classification issues, Authorized Representation, Performance Evaluation, Vigilance, and Post-Market Performance Follow-Up.
The IVDR will bring about a stricter, two-fold regimen of supervision – there will be more rigorous surveillance by Notified Bodies to reduce risks from unsafe devices and greater scrutiny of NBs itself. As a result, the requirements for qualified NB staff have increased considerably.
Expanded Product Scope
IVDs will now include Genetic testing and diagnostic services including stand-alone software, such as mobile medical apps which may now be considered IVDs in line with the interpretation in MEDDEV 2.1/6. Self-testing devices have been redefined and additionally, the concept of single use devices intended to be used during a single procedure, which were part of the MDD, have been introduced in the IVDR as well. The IVDR also introduces the concept of companion diagnostics, kits, and new rules for in-house tests which will be detailed in the following article.
Greater Importance of Technical Documentation & Conformity
Manufacturers are now required to supply the appropriate Competent Authorities (CA) with all information necessary to show conformity, further authorizing them to share that information with patients or their representatives claiming compensation. The manufacturer is required to provide full Disclosure on Design, Production and Quality Testing.
Identification of ‘person responsible for regulatory compliance’
It remains to be seen what the scope of the aforementioned role will be, post enforcement of the IVDR. As the Authorized Representative is made jointly culpable for defective devices, non-European manufacturers may expect to face higher costs and more complex processes to enter the European market compared to their European colleagues.
Unique device identification (UDI) for improved traceability
The basic device identifier (Basic UDI-DI) must also be referred to in an IVD’s Declaration of Conformity and on the certificates of Class B, C, and D devices.
No “grandfathering” provisions
Regardless of prior approvals, recertification will be mandatory for all currently approved in vitro diagnostic devices adhering to the new requirements.
More Stringent Requirements for Post Market Surveillance (PMS) and Post Market Clinical Followup (PMCF)
The IVDR introduces clinical evidence and post-market performance follow-ups as new concepts for IVDs, wherein performance evaluation is an ongoing process that evaluates the device during its life-cycle with clinical evidence to support the intended purpose. Outlined in a strong post-market performance evaluation plan, this will ensure identification of outdated and under-performing devices for noncompliance, which may stimulate innovation. To be continued…
What this means for the Industry:
With more comprehensive laws governing the regulation and delimiting the scope of IVDs than its predecessor, the IVDR may lead to a completely new infrastructure for innovation in the field of IVDs in the European Union. Although some experts predict that the increased requirements for current clinical performance data may discourage the development of innovative tests for rare conditions, institutions will have a clear role in how they should manage and safeguard their in-house tests. It is expected that this new approach will also affect staffing at Competent Authorities, NBs, and the EOs, manufacturers included.
The IVDR stresses the importance of establishing device performance through Technical Documentation, Clinical Performance, Scientific Validity and Analytical performance. It should also be noted that Technical Documentation does not end with a submission, but should be continuously updated throughout the device lifecycle. Finally, since the classification of a device can influence the documentation required, manufacturers should be mindful of the classification rules to classify products accurately and efficiently.
Thus, the IVDR will introduce significant changes to European regulatory requirements for IVD devices, in turn requiring a more comprehensive approach, ranging from IVD development, to market surveillance, to end usag. Greater emphasis on risk management strategies and PMCF will ensure greater accuracy of claims and safety of devices.