Why the IVDR is changing the way we develop diagnostic devices

The In Vitro Diagnostic Regulation (IVDR) (EU) 2017/746 [1] is the new EU legislation applicable to in vitro diagnostic (IVD) medical devices. Having come into force on the 25 May 2017 this started a five-year transition period for manufacturers as it replaces the In Vitro Diagnostics Directive (IVDD) 98/79/EC. From 26 May 2022 all new in IVD certifications must be under the IVDR, although existing certificates issued under the IVDD can have a grace period up to 27 May 2024.

There has been much discussion and even concern within the IVD community about just how significant the changes are in moving to the IVDR. BSI have identified four major changes [2]:

1. Extension of the scope “to include ‘lifestyle tests’ by including the elements of ‘indirect medical purpose’ and ‘prediction’ in the definition to include ‘nutrigenetic tests and lifestyle tests’, which are not covered by the IVDD.

2. Introduction of a risk based classification system from A to D (low to high risk). “With notified bodies having to perform conformity assessment on all but class A devices, the landscape is dramatically changing in terms of files to be reviewed and audits to be performed pre- and post- market”.

3. The conformity assessment routes for IVDs are amended to fit the new classification logic. “As a consequence 80% of all IVDs will need to be certified by a notified body under the IVDR, as compared to 20% currently under the IVDD”.

4. “Clinical performance studies will be required to support the CE mark under the IVDR. As a consequence IVD manufacturers will need to produce significantly more clinical evidence.”

One of the biggest impacts is on notified bodies, which face a huge increase in workload driven by the more stringent requirements of the IVDR.

For IVD manufacturers these changes are also having significant impacts for those involved in preparing technical documentation for new IVD device designs, and for those updating technical documentation for existing IVDs that will need to be re-certified under the requirements of the IVDR to continue to be marketed when their existing IVD certification ends. Much of the administrative work falls on the shoulders of manufacturer’s regulatory and quality management departments, but designers and developers are impacted too.

Implications of the IVDR for designers and developers

From a historical point of view, the IVDR and MDR were a response to public scandals regarding poor devices that were not appropriately developed and controlled in manufacture.  It was felt that there were also insufficient processes in place to effectively monitor clinical feedback from product in use. As a result, regulators have implemented a more comprehensive and elevated risk classification system that is now more significant for many IVDs. The IVDR requires developers to use more rigour and to gather better evidence for the effectiveness and safety of their devices, all of which must be well documented and suitable for notified body conformity assessments.

Of course, for product developers the technical skills required to develop a new IVD are not necessarily affected by the IVDR; but major aspects of the depth and manner in which it is done will almost certainly change, especially if the type of device being developed is effectively now in a higher risk class, requiring notified body involvement instead of self-certification. Some key aspects of device development that need to be adjusted in light of new requirements from the IVDR are discussed below.

Planning is essential to make sure that development projects are ‘IVDR ready’

It may seem obvious, but this is probably the most significant thing that can be done to help teams developing new IVD devices. Development procedures may need to be updated to reflect the need for increased design process controls, better design documentation and greater evidence of real world device performance. Consideration should be given to the increased focus on clinical performance studies, meaning that additional prototypes may be required during development, and better evidence of the suitability and validity of these prototypes will also be needed. Notified bodies will want to review the development plan as part of the conformity assessment, so these plans need to be created properly at the project outset, as it is hard if not impossible to create the right evidence retrospectively.

Integration of risk analysis with design requirements

With increased emphasis on risk management, it is even more important to integrate risk analysis with the creation, development and documentation of design requirements. Increased emphasis on considering requirements for usability and in particular risks associated with use errors and handling difficulties should be expected. Design requirements must also include consideration of support for the device lifecycle, such as service, maintenance, updates and cybersecurity, end of life, etc.

An increased focus on development rigour and design documentation

Consideration needs to be given to the collation and documentation of evidence that design requirements and identified risk control measures are correctly implemented and verified. In order to support this, it is likely that more detailed engineering analysis, well documented tolerance analysis, mathematical modelling and computer aided simulations will be needed. Reasonable scenarios and permutations should be analysed as early as possible, which in our experience can often discover latent problems at significantly less cost and time impact than finding a problem in late stage tests or worse, in the field. Additional technical skills and software tools may be needed to support the greater diligence that is now required compared with what was previously considered acceptable.

Evidence-based development and testing

From extensive experience of mitigating and refining design concepts that have been initiated by other parties, we have observed that it can be all too easy for development engineers to see and understand something about their design, but not to capture or record this sufficiently at the time. An evidence-based design philosophy is a cornerstone for our development work, underpinning and informing our important development decisions. But, of course, technical evidence is only of value if it is recorded and communicated clearly amongst key project stakeholders.

Summary

Ultimately the IVDR is about ensuring safe and effective devices reach the market. Proactive manufacturers should see the IVDR as an opportunity to encourage better planning, better understanding of requirements, more rigour in development and increased evidence to inform decision-making. Of course it is important that development programmes do not become mired in excessive process administration and documentation but the new requirements of the IVDR, when executed well, can only be a good thing for driving the development of safer and more effective devices that helps patients and healthcare professionals achieve better outcomes.

References and website links

[1] Official Journal of the European Union, REGULATION (EU) 2017/746 - https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/

[2] How to prepare for and implement the upcoming IVDR – Dos and don’ts - https://www.bsigroup.com