State of the art
What does it actually mean in the EU MDR and IVDR?
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.
Yet, “state of the art” can change depending on context. 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 continuously changing as medical treatment advances. As medical guidance changes, new innovations are made, and the term evolves, so what is acceptable today may become outdated.
Because “state of the art” only relates to devices developed and approved for sale in the marketplace. So 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 still in the testing phase and one that has received CE Marking. EU medical device regulators consider the latter state-of-the-art. The former is not unless it receives a CE Mark.
We want to help manufacturers understand this further and provide guidance in this paper. We’ll 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.” Hence, “the current state of all competitive treatment options” is a better definition of state of the art.
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. This is based on 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 clarify what 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 a continual, iterative process that must meet the following criteria, according to the regulation:
- 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.”
Notified bodies frequently ask for physical and/or chemical information. ISO 10993-1:2018 specifies this 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. 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. This highlights that the E/L data from chemical characterisation is crucial.
The point is 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 should determine NB requirements. You can then 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 technically, biologically, and clinically equivalent to the device under evaluation. Devices are “similar” when they fall under the same generic device category and have the same or similar intended purposes.
A database allows US manufacturers to find legal predicate devices. Data from these predicate devices can support new medical device risk claims and speed regulatory approval.
Unfortunately, the EU doesn’t have such a database. Manufacturers must have enough access to data on the equivalent device to claim equivalence. For high risk devices, a contract must be in place. It must be ongoing, allowing full access to technical documentation. The likelihood of claiming equivalence in the EU has decreased due to 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. This must be in accordance with the ISO 10993 family of standards, before collecting clinical data. By identifying hazards, manufacturers can initiate biocompatibility, simulated-use, and other focused analysis before clinical testing. When the time comes, this preclinical data can also be invaluable in supporting clinical findings. Manufacturers can manage risk thoroughly, while ensuring 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 technical documentation scrutiny during your next surveillance audit. Notified Bodies increasingly want to see that you have conducted a thorough assessment of alternative treatment methods for the same indications.
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. 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 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. Both manufacturers and Notified Bodies can use this.
For EU IVDR, manufacturers must specify and justify the amount of clinical evidence needed to demonstrate conformance to the device’s characteristics and intended purpose. 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 need to be demonstrated with reference to the 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 lead to 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 clearly explain the SoTA for their device to the Notified Body, it will leave various areas of the Technical Document open to scrutiny and create uncertainty about conformance.
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 should therefore be formulated by Clinical Affairs specialists, who are seasoned researchers and medical writers.
Manufacturers without this expertise should consider partnering with an experienced consultancy to assess 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!
Remediating a problematic Clinical Evaluation Report
Risk Management
