IVDR: State-of-the-Art for In Vitro Diagnostic Medical Devices
With the updates to the European Medical Device and In Vitro Diagnostic Device Regulations (MDR 2017/745 and IVDR 2017/746, respectively), the requirements for clinical evidence were increased by the regulatory authorities. 1
Part of the development of clinical evidence for both medical and in vitro diagnostic devices is establishing your device in the context of the state-of-the-art.
When some people hear state-of-the-art, they think about the newest technologies, novel devices, and top-tier innovations.
In the context of clinical evidence, state-of-the-art means the current knowledge and devices on the market for a specific medical condition, i.e., the accepted standard clinical practice.
State-of-the-Art for In Vitro Diagnostic Devices
State-of-the-Art is not defined anywhere in the IVDR.
However, state-of-the-art is defined in the Medical Device Coordination Group Document MDCG 2022-2: Guidance on general principles of clinical evidence for In Vitro Diagnostic Medical Devices (IVDs) as:
“State-of-the-art: Developed stage of current technical capability and/or accepted clinical practice in regard to products, processes, and patient management, based on the relevant consolidated findings of science, technology, and experience.
Note: The state-of-the-art embodies what is currently and generally accepted as good practice in technology and medicine. The state-of-the-art does not necessarily imply the most technologically advanced solution. The state-of-the-art described here is sometimes referred to as the ‘generally acknowledged state-of-the-art.”
State-of-the-art is not static
While state-of-the-art could be considered a one-time deal, it is not – it is a crucial step to compliance with the many new requirements of new IVDR. It must be updated throughout the lifetime of your device as part of post-market surveillance activities.
Article 56 of the IVDR states that:
“The clinical evidence shall be such as to scientifically demonstrate, by reference to state of the art in medicine, that the intended clinical benefit(s) will be achieved and that the device is safe.“
Essentially, to establish the clinical benefit and safety of your device, you must put it into the context of other in vitro diagnostic medical devices and technologies already on the market and establish that your device performs as well as those other in vitro diagnostic medical devices.
Challenges with State-of-the-Art
As with many other parts of the MDR and IVDR, state-of-the-art is a challenging concept.
Almost all manufacturers must comply with state-of-the-art, but guidance is needed.
There is no regulation-based definition of state-of-the-art available, only the definition mentioned above from the MDCG guidance documents.
This is despite the term “state-of-the-art” being used 20 times in the IVDR.
And while the MDCG guidance is as close to an official document as possible, it is not legally binding.
Following that, “state-of-the-art” is used inconsistently throughout the regulation.
It is described as the latest, generally acknowledged, and current state-of-the-art throughout the regulation.
Despite the problems with the term itself and its use, the most common challenges facing medical device manufacturers for state-of-the-art is to do with the content of the section itself.
Side note: while some notified bodies prefer reviewing a separate state-of-the-art report, including it as a section in the performance evaluation report is perfectly fine.
State-of-the-art for New Devices
A genuinely new device that employs innovative techniques cannot be compared to devices already on the market and will essentially need to establish its own state-of-the-art.
Novel medical devices will instead need to provide expert opinions or other key input from leaders in their fields to support that the in vitro diagnostic medical device conforms to its intended clinical benefit.
Likewise, it becomes exceptionally important to closely monitor and document the routine use of the device as part of post-market surveillance activities.
State-of-the-art is of course not static. On the contrary, technologies and medical devices in the market are evolving with startling speed.
This makes monitoring state-of-the-art continuously throughout the lifetime of the device of critical essence.
In vitro diagnostic medical device manufacturers must update their state-of-the-art with information from the EU and the accepted clinical practice every time the performance evaluation report is updated.
State-of-the-art data has many sources, the most critical example being:
- Clinical guidelines
- Such as from the World Health Organization (WHO), the UK National Institute for Health and Care Excellence (NICE), European and national clinical guidelines, etc.
- International standards for the same or similar medical devices
- Literature searches and reviews from scientific journals
- such as PubMed, Embase, and Invivo
- Clinical trial registries
- such as clinicaltrials.gov and the Cochrane Library European technology application associations
- Surveys performed in clinics and laboratories for routine diagnostic information
- Clinical performance studies for similar devices (if you have access to them)
A particular challenge for IVDs is that while a test may no longer be considered the standard of care, it can still be recommended for use when the primary test is unavailable.
In that case, manufacturers can justify why their device remains used in clinical practice, although another type of IVD is considered state-of-the-art.
Finding a Good Comparator Device
Comparing the performance of your device to similar medical devices in the market is the simplest way to substantiate the benefit-risk ratio analysis and clinical benefit of the device.
To do so, you must find a comparator device with the same intended use as your device.
If the manufacturer already has clearance with the US FDA, using the devices included in the 510(k) is, of course an excellent place for manufacturers to start.
If not, most manufacturers will have an idea of similar devices already in the market.
You do not need the complete technical documentation for similar devices – that is only required for claiming equivalence.
You only need some key information, such as intended purpose, use, technology, method of function, etc., to use them as similar to other devices.
Why You Need Good State-of-the-Art
Most manufacturers have the data they need to demonstrate state-of-the-art, but only a few manufacturers use the data correctly.
State-of-the-art feeds directly into the risk acceptability and benefit-risk ratio analysis of your device.
Not to mention that many notified bodies specifically look for in-depth assessments of the performance and safety of your device compared to alternative treatment methods for the same clinical indications.
If you do not use the state-of-the-art data available to you correctly, your conformity assessment could be severely delayed with non-conformities from the notified bodies.
Delays in the regulatory world always mean a drain on resources and the mental sanity of your staff.
Instead the risk of complicating your conformity assessment, reaching out to someone with state-of-the-art experience who can help you get it right the first time might be worth it.
You can reach out to Citemed.