The IVDR has brought about a paradigm shift in the regulatory framework for IVDs placed on the EU market and finally aligned the EU framework with International Medical Device Regulators Forum (IMDRF) principles and guidelines. Despite these principles and guidelines having been adopted by regulatory authorities in other markets several years ago (e.g. Australia), and the recent IVDR amendments further extending the transition timeframes, IVDD device manufacturers who don’t have a commercial presence in these other markets are facing resource management constraints in their transition to the IVDR.
IVDD and IVDR differences impacting manufacture resources
In this article, we briefly discuss those differences between the IVDD and IVDR that, based upon our interactions with IVD manufacturers, have had the greatest impact on their resources as they work towards IVDR conformity.
1. Rules-based classification system/conformity assessment procedures
With self-certified (non-list A/B, non-self-testing) IVDs representing approximately 90% of all devices CE marked under the IVDD and approximately the same percentage of devices now requiring conformity assessment with Notified Body involvement, this difference has easily shown itself to have had the greatest impact across the IVD industry and has been the main contributing factor (combined with the shortage of Notified Bodies resources for conformity assessment) for further extensions to the IVDR transition timeframes.
To limit the impact on their resources, it is recommended that manufacturers’ take the time to review their product portfolios and identify those IVDs that have a more critical role commercially in the EU. For example, while all self-certified Class A devices placed on the EU market from 26 May 2022 must be fully compliant with the IVDR, those manufacturers that have paused marketing devices in the EU since this date, while they work towards regulatory compliance, should prioritize Class A devices necessary to support other legacy devices place on the market, (e.g. multi-assay instrument platforms).
For those legacy devices that are subject to Notified Body involvement under the IVDR, manufacturers should routinely engage with the Notified Body to verify timeframes for QMS assessment and technical documentation file review. We have already observed Notified Bodies push out their timelines for medical device technical documentation file reviews due to their resource constraints and we expect to see the same for IVDs. Keeping on top of these changes can help manufacturers coordinate their internal resources for priority compliance activities.
2. Performance evaluation
While requirements related to IVD analytical and clinical performance existed under the IVDD, including the requirement for performance evaluation studies, “performance evaluation,” did not exist as a process in an analogous manner to, “clinical evaluation,” for non-IVD medical devices.
To maximize resource utilization in the generation of performance evaluation documentation, manufacturers are recommended to invest the time necessary to establish a robust performance evaluation process in their QMS, including establishing:
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- Procedures for performance evaluation, including literature search and the management of performance evaluation studies.
- Templates for all performance evaluation documentation required under the IVDR (Performance Evaluation Plan, Scientific Validity Report, Analytical Performance Report, Clinical Performance Report, Literature Search Protocol, and Literature Search Report) to help standardize the approach as much as possible.
Manufacturers of self-certified legacy devices that continue to be self-certified under the IVDR who have not yet experienced a Notified Body technical file review for a non-self-certified device face a real risk of employing a non-compliant approach to performance evaluation, particularly in the case of foreign manufacturers whose EU Authorized Representative is not performing adequate due diligence or technical documentation reviews. In such instances, where the same non-compliant approach has been applied for multiple performance evaluations, the manufacturer faces a significant impact on its resources as it will need to reperform the respective performance evaluations. Of particular note for manufacturers of such devices, they should not make the (incorrect) assumption that just because they have appropriately justified the non-applicability of scientific validity and specific clinical performance characteristics a literature search is unnecessary.
Additionally, for those IVDs that do possess specific clinical performance characteristics, manufacturers should review their product portfolios and determine device novelty for each device utilizing the criteria established in their performance evaluation process. Once this is determined, manufacturers are recommended to review the existing clinical performance data and identify existing gaps for IVDR conformity, particularly identifying those devices that are highly likely to require performance evaluation studies as these will have the highest resource burden.
3. Post-market surveillance (PMS)
As is the case with performance evaluation, we have also observed manufacturers of self-certified devices possessing a non-compliant approach for PMS. This has also been observed for manufacturers of “up-classified” legacy devices who have yet to undergo Notified Body technical documentation file review. And again, due to IVD manufacturers typically having sizeable product portfolios, employing a non-compliant approach across multiple devices can place an unnecessary burden on their resources. Areas of non-conformity related to differences between the IVDD and IVDR include:
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- No suitable indicators and threshold values for benefit-risk analysis are covered in the PMS Plan;
- No indication of the methods and protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation period for trend reporting in the PMS Plan;
- No PMPF plan or justification as to why PMPF is not applicable.
Regarding the third bullet point above, in particular, manufacturers should note that under the IVDR both general and specific PMPF methods/procedures are called out under Section 5.2(a) & (b), Part B, Annex XIII of the IVDR, and that in all circumstances where a manufacturer has determined that PMPF is not applicable an appropriate justification must be provided – it is insufficient to simply state that PMPF will not be applicable.
4. Technical file compilation
While all the points above have a direct impact on technical documentation file compilation activities, compilation of the technical file itself (if not properly planned) can also have a significant impact on resources. For example, we have observed manufacturers of devices self-certified under the IVDD that have:
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- Incorrectly identifying products as “accessories” under both the IVDD and IVDR despite such products not falling within the definition of “accessory for an in vitro diagnostic medical device” established under Article 2(4) of the IVDR (and corresponding definition under the IVDD), such as control materials or calibrators placed on the market separately;
- Not correctly identifying or describing, and subsequently not controlling, products as, “accessories”;
- Incomplete device descriptions which are not aligned with the content requirements under Section 1, Annex II, especially regarding the identification of similar devices and, in the case of US-based manufacturers, incorrect identification of UDI-DIs as Basic UDI-DIs.
- Carrying over errors from their IVDD Essential Requirements Checklists to their IVDR GSPR Checklists, including inappropriately indicating applicable GSPRs as non-applicable, not providing appropriate justification for non-applicable GSPRs, no indication of the versions of standards applied and not applying document controls to the checklist.
All the above items, if not appropriately addressed up front by the organization during the compilation of their first IVDR technical documentation file, run the risk of being replicated across multiple technical files and thereby placing a further strain on resources.
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