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State of the art

What does it actually mean in the EU MDR and IVDR?
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State of the art
What does it mean in the EU MDR and IVDR context?
The common interpretation of the phrase "state of the art refers to the current level of
development or advancement of a particular technology, product, or field. Simply put the latest
and the greatest technology has to offer. It can include the most recent and sophisticated
versions of the technology, as well as any other advancements or breakthroughs that are
considered to be cutting-edge.

However, is noteworthy to consider that the exact definition of "state of the art" can vary
depending on the context in which it's used. This is surely the case with medical devices or IVD,
here "state of the art" refers to the current accepted standard of care. To concretely define it
you need to combine current regional medical guidance, regulatory frameworks and industry
standards. Meaning that the "state of the art" is actually a moving target as medical care
progresses, so what is acceptable today may quickly become outdated as medical guidance
updates, new advancements and innovations are made, so the term is constantly evolving.

Because "state of the art" only relates to devices that have been developed and approved for
sale in the marketplace, there is some misunderstanding regarding the regulatory system for
medical devices and IVDs. There are significant differences between a brand-new, cutting-edge
digital imaging system that is still in the testing phase and one that has received CE Marking. The
latter is regarded as state-of-the-art by EU medical device regulators, whereas the former is not
unless it receives a CE Mark.

We want to assist manufacturers to understand this further and provide guidance to help explain
what the state of the art is and how it can help make your CE submission successful.

What is state of the art?

According to the MDCG, “state of the art embodies what is currently and generally accepted as
good practice in technology and medicine. This 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’’.

MEDDEV 2.7/1 rev 4 adds some insight: “The state of the art embodies what is currently and
generally accepted as good practice. The state of the art does not necessarily imply the most
technologically advanced solution.” Thus, it is more useful to think of state of the art as meaning
“the current state of all competitive treatment options.”

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So, “state of the art” essentially refers to what the industry generally accepts as good practices.
Yet, that explanation's ambiguity leaves device manufacturers and notified entities without
certainty. Manufacturers are unsure whether the term "state of the art" applies to the devices
themselves, the methods used to create them, the analytical techniques used to test them, or
the clinical data (from literature or clinical investigations). State of the Art definitions can be at
the discretion of notified bodies, based their knowledge of the MDR and EU regulatory law.

State of the art is, in the end, a dynamic concept. Examining MDR language related to
standardisation, risk management, and clinical data (medical standards of care and research)
may help to clarify what the regulatory authorities anticipate from the industry or influence their
point of view.

State of the art Risk Management

Safety and device performance are equally important components of medical device state of the
art. Manufacturers must create, record, execute, and maintain a device safety risk management
system in accordance with MDR Article 10. Risk management is described in the regulation as an
ongoing, iterative process that must meet the following criteria:
• All risks related to the device must be minimised to the greatest extent possible;
• Manufacturers must implement a risk management system and apply it to each device;
• State-of-the-art risk controls must be used;
• Human factor risks must be addressed;
• Risk mitigation measures must be effective for the lifecycle of the device;
• Risk mitigation measures must not be impacted by transporting or storing the device; and
• The advantages of using the device must outweigh any foreseeably residual risks.

State of the art risk management is not specifically addressed in the requirements list, except to
say it must be used.

Let’s look at an example of how a non-harmonized standard can be used to comply with state of
the art risk management. Article 10 offers a compelling justification for chemical characterization
using extractables/leachables testing without specifically addressing the analytical method.

It says: “Devices shall be designed, manufactured, and packaged in such a way as to minimise the
risk posed by contaminants and residues to patients, taking account of the intended purpose of
the device, and to the persons involved in the transport, storage, and use of the devices.
Particular attention shall be paid to tissues exposed to those contaminants and residues and to
the duration and frequency of exposure.”

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Notified bodies frequently ask for physical and/or chemical information as specified by ISO
10993-1:2018 in order to comply with the above-mentioned guidance. This is frequently
accomplished using chemical characterisation data that complies with the revised ISO 10993-
18:2020 standard. In the past, manufacturers could demonstrate risk management using data
from literature reviews of their materials, but the increased attention paid to advanced chemical
analyses has changed that.

To distinguish between "same materials or substance" and "similar release characteristics of

substances," MDCG's article on equivalence specifically cites ISO 10993-1:2018, 10993-18:2020,
and 10993-17:2002. The distinction is made to account for the fact that designing,
manufacturing, and transporting medical devices may introduce foreign chemical components
even when the raw materials are the same. In this case, a literature review is unlikely to cover
these contaminants and residues which highlights that the E/L data from chemical
characterisation is crucial.

The point being that even though the EU has not harmonised ISO 10993-18:2020 across all
member states, regulators consider it as state of the art. Manufacturers are recommended to
find out which NBs require what. This can help determine what studies are needed and which
NB is best suited for you to work with.

State of the art Clinical Data

State of the art risk management in medical devices must cover equivalent and similar devices.
"Equivalent" refers to a legally marketed device that is technically, biologically, and clinically
equivalent to the device under evaluation. On the other hand, devices are deemed "similar"
when they fall under the same generic device category and have same or similar intended
purposes.

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In the US, manufacturers can look up predicate devices that are legally marketed in the US using
a database. Data from these predicate devices can be used to support the risk claims made for a
new medical device and speed up regulatory approval.

Unfortunately, the EU doesn’t have such a database. Manufacturers must have enough access
to data on the equivalent device in order to claim equivalence. For high risk devices, a contract
must be in place, on an ongoing basis that allows full access to the technical documentation. The
likelihood of claiming equivalence in the EU has decreased as a result of these requirements. This
is particularly true for devices manufactured by third parties.

Manufacturers can enhance the trajectory of their devices by putting them through biological
evaluation in accordance with the ISO 10993 family of standards before collecting clinical data.
Manufacturers can obtain a head start on biocompatibility, simulated-use studies, and other
targeted analysis that may be required before clinical testing by identifying potential risks. When
the time comes, this preclinical data can also be incredibly helpful in supporting clinical findings.
It will be easier for manufacturers to manage risk thoroughly while making sure that only "state
of the art" products are available with greater clinical and preclinical expert participation.

What’s needed in your technical documentation?

You must be able to demonstrate that you conducted a thorough analysis of the current state of
the art. This analysis includes:
▪ A systematic literature review that defines all aspects of SoTA as per MEDDEV 2.7.1 and
MDCG 2020 Clinical Evaluation Assessment Report. Listing clinical safety and performance
endpoints found in the literature to justify your endpoints for your device.
▪ Justification of level of novelty or Well-Established Technology though clinical literature,
medical guidelines, and medical device database information.
▪ Medical Device post market category insights to identify hazards and harms of the device
category (similar devices). Rates of device failures and adverse event occurrence rates. To
take to your Risk Management process and use within your benefit-risk justification.
▪ Clinical data of the SoTA’s safety and performance endpoint range. For example, the
incidence rates of complications for similar devices and alternative treatments.
▪ Outline how you have used common and harmonised standards (validated industry
standards/mythologies) in your validations to demonstrate conformity to the EU
MDR/IVDR.

You should anticipate additional scrutiny during your next surveillance audit as Notified Bodies
increasingly want to see that you have conducted a thorough assessment of alternative
treatment methods for the same indications.

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While assessing the risk acceptability of your devices, implementing risk control measures, and
determining the clinical benefit of your devices, you must consider state of the art. As a result,
taking into account the state of the art is important for determining the device's benefit-risk
ratio, and you should do so in your clinical evaluation report (CER). The benefit of your device is
reduced, and the risk side of the benefit-risk equation is increased if two other devices that are
technically superior and present a lower risk than yours have been on the market for decades.

Information on the medical condition being managed by the device, how it will develop naturally,
comparable devices, or other devices and medical alternatives that are accessible to the target
population. The state of the art specification in MEDDEV 2.7/1 rev 4 and MDCG 2020-6 provides a
framework for evaluating the device's performance and safety. This can be used by both
manufacturers and Notified Bodies.

For EU IVDR, the amount of clinical evidence needed to demonstrate conformance in respect
to the device's characteristics and intended purpose must be specified and justified by
manufacturers. Clinical evidence, performance evaluation, and study requirements for IVDs are
defined related to the state of the art in medicine.

References for clinical evidence that a clinical benefit will be achieved and that devices are safe
needs to be demonstrated with reference to state of the art.

CLIN-r+ Recommendations
Notified bodies are given the authority to define “state of the art” in accordance with their
expertise and understanding of the law. Where the manufacturer provides an ill-defined or no
SoTA, it opens the door for the Notified Body to impose their interpretation of the SoTA.
Uncertainty could result in the need for expensive clinical trials, or worse - no CE mark being
granted.

Hence defining the ‘state of the art’ should be the starting point in the development process by
any manufacturer or innovator in MedTech. If a manufacturer cannot demonstrate to the
Notified Body a clear understanding of what the SoTA is for their device, it will leave various areas
in the Technical Document exposed to scrutiny and sow uncertainty if conformity is achieved.

A state of the art literature review gives a wealth of information by overviewing the performance
and safety data, as well as defining the technologies clinical benefits, disadvantages, risks, and
limitations. It also reviews similar devices and medical alternatives for the intended populations
and medical indications to benchmark what is acceptable. It contains powerful strategic insight
and hence should be formulated by Clinical Affairs specialists who are seasoned researchers and
medical writers.

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Manufacturers without this expertise should consider partnering with an experienced
consultancy when assessing standards, risk, and clinical data. Consultancies also come with
resources such as systematic review software, access to literature databases, and industry expert
reviewers, helping expand your companies’ capabilities cost-effectively.

Should you have any questions or need professional assistance, CLIN-r+ has a wealth of
experience in clinical evaluations and literature searches to call upon. Get in touch!

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