The concept of equivalence in the European’ MedTech sector
In Europe, medical device manufacturers with products on the market have long used clinical data from equivalent devices to confirm the clinical safety and performance of their devices. Using clinical data and clinical evidence from equivalent devices allowed manufacturers to save time and avoid redundant clinical investigations.
The idea of using an equivalence to obtain clinical data was introduced in the nineties in both the Medical Device Directive (MDD) and the Active Implantable Medical Device Directive (AIMDD). However, the directives did not specify which parameters needed to be used in the establishment of equivalence. The guidance document MEDDEV 2.7/1 rev 4, released in 2016, identified clear criteria to establish equivalence and the Medical Device Regulation (MDR), released just one year after the MEDDEV, reinforced these criteria. To harmonize and align requirements between the MEDDEV guidance document and the MDR, a new document was released in 2020: “MDCG 2020-5 Clinical Evaluation – Equivalence”.
With these recent changes, medical device manufacturers are facing the challenge of re-evaluating their equivalence claims and deciding whether additional clinical evidence is required.
Clinical Evidence from Equivalent devices
The MDR specifies that clinical data contributing to the clinical evaluation can come from the device under investigation or from a device for which equivalence has been demonstrated. This data can take the form of clinical investigations, studies, reports published in peer-reviewed literature or clinically relevant information coming from post-market surveillance.
Evidence from similar devices that are not equivalent may also support clinical evidence. However, it will not generally constitute sufficient clinical evidence for substantiating compliance with the essential requirements (except for particular low risk, well-established technologies).
Requirements regarding demonstration of equivalence
The MDR (Annex XIV, Part A) establishes that, in order to demonstrate equivalence in relation to other devices, three characteristics must be considered when demonstrating equivalence: technical, biological, and clinical. These characteristics shall be investigated and differences between devices should be disclosed.
In addition, the MDR specifies that “It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence”. If a manufacturer cannot demonstrate sufficient levels of access to presumed equivalent device data, equivalence cannot be claimed for the purpose of clinical evaluation.
Specific requirements for class III and implantable medical devices
According to MDR Article 61(4), demonstration of equivalence might allow manufacturers of implantable and class III medical devices not to perform a clinical investigation if:
the device has been designed by modifications of a device already marketed by the same manufacturer,
equivalence can be demonstrated according to the MDR between the two devices, and
the clinical evaluation of the marketed device is sufficient to demonstrate conformity with the relevant safety and performance requirements
For implantable and class III devices claiming equivalence to an already marketed device not manufactured by the same company, in addition to the above requirements, the manufacturer must have a contract in place to allow full access to the technical and clinical documentation of the equivalent device on an ongoing basis (MDRArticle 61(5)). In this case, it is also required that the initial clinical evaluation of the equivalent device has been performed in compliance with MDR requirements and that the device is certified under the MDR. The MDCG 2020-5 further clarifies that it will not be possible to claim equivalence if that device is certified under the MDD.
Requirements for medical devices other than class III and implantable
For devices other than implantable and class III devices, the MDR does not specify whether the equivalent device has to be marketed within the EU (Article 61(3)). According to MDCG 2020-5 equivalence can be claimed to devices certified under MDD or MDR, and even to devices that are not CE-marked (if the device fulfils all relevant MDR requirements regarding equivalence and clinical evaluation). The requirements for devices that are not CE-marked include:
that the manufacturer has sufficient levels of access to the data
those clinical investigations were conducted following good clinical practices (ISO 14155)
that the clinical data meet the MDR requirements and is transferrable to the European population.
If the equivalent device is from another company, there is no requirement of a contract between the manufacturers for regulating the access to the technical documentation.
MEDDEV 2.7/1 Rev 4 also contemplates that clinical data of a non-CE-marked medical device can be used for clinical evaluation, and the recommendation is similar to that provided in MDCG 2020-5.
MDCG 2020-5: Comparison between MEDDEVV 2.7/1 Rev.4 and MDR
The MDCG 2020-5 guidance document provides additional insights regarding equivalence and addresses the differences between MDR and MEDDEVV 2.7/1 Rev.4. In addition, MDCG 2020-5 specifies the requirements for clinical evidence regarding technical, biological, and clinical equivalence. The following table evidence equivalence characteristics and criteria between MDR and MEDDEVV 2.7/1 Rev.4
MDR, Annex XIV Part A (3)
MEDDEV 2.7/1 rev 4, Appendix A1
The device is of similar design; is used under similarconditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements.
– Be of similar design, and
– Used under the same conditions of use, and – have similar specifications and properties (e.g. physicochemical properties such as type and intensity of energy, tensile strength, viscosity, surface characteristics, wavelength, surface texture, porosity, particle size, nanotechnology, specific mass, atomic inclusions such as nitrocarburizing, oxidability), and – use similar deployment methods (if relevant), and – have similar principles of operation and critical performance requirements.
The device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables. Exceptions can be foreseen for devices in contact with intact skin and minor components of devices; in these cases, risk analysis results may allow the use of similar materials taking into account the role and nature of the similar material.
Use the same materials or substances in contact with the same human tissues or body fluids. Exceptions can be foreseen for devices in contact with intact skin and minor components of devices; in these cases, risk analysis results may allow the use of similar materials taking into account the role and nature of the similar material.
The device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.
– used for the same clinical condition (including when applicable similar severity and stage of disease, same medical indication), and – used for the same intended purpose, and – used at the same site in the body, and – used in a similar population (this may relate to age, gender, anatomy, physiology, possibly other aspects), and – not foreseen to deliver significantly different performances (in the relevant critical performances such as the expected clinical effect, the specific intended purpose, the duration of use, etc.)
The characteristics listed in the first paragraph shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification.
For assuming equivalence, – all three characteristics (clinical, technical, biological) need to be fulfilled; – similar means that no clinically significant difference in the performance and safety of the device would be triggered by the differences between the device under evaluation and the device presumed to be equivalent
Tips to demonstrate equivalence
MDCG 2020-5 Annex I includes an example table that can be used to demonstrate equivalence. The table includes an exhaustive list of the technical, biological and clinical characteristics that should be assessed. An additional column is added to include the result of the assessment and any identified differences. At the end of the table, scientific justification why there would be no clinically significant difference in the safety and clinical performance of the device is expected.
To make a comprehensive demonstration of equivalence:
use tables that describe the characteristics of the two devices and note both their similarities and differences
clearly and explicitly state all differences between the devices
critically analyze these differences to determine their likely impact on safety and performance.
include illustrations of the devices highlighting similarities and differences
Equivalent vs Similar
Furthermore, the difference between the equivalent and similar is addressed in MDCG 2020-5.
If established that the clinical, technical and/or biological differences result in no clinically significant difference in device safety and performance, then the device may be considered equivalent to the subject device. To establish equivalence, the differences between the two devices will need to be minimal. You need to provide evidence to substantiate the claim, such as pre-clinical (bench testing or in vivo studies) and/or clinical (clinical investigation or post-market) data.
However, multiple and/or significant differences will compromise claims of equivalence. In these scenarios, the devices may be considered similar.
The manufacturer’s responsibility is to ensure that all relevant information relating to the comparable device is provided for clinical assessment – the clinical data that demonstrates its safety and performance.
The following flowchart guides how to demonstrate equivalence:
So, is it really the end of the equivalence route for medical device manufacturers?
Despite the increment in requirements to demonstrate equivalence, particularly for class III devices, medical device manufacturers still have the chance of demonstrating equivalence and using clinical data of equivalent devices to optimize their CE-marking process. With the implementation of the new regulation and the end of the transition phase coming soon, it is important that manufacturers of new devices perform an analysis of potentially equivalent devices. For devices already CE-marked under the MDD, medical device manufacturers should perform a gap assessment of their previous equivalence analysis and associated clinical data.
AKRN Scientific Consulting can assist medical device manufacturers with the demonstration of equivalence in compliance with the requirements of the MDR 2017/745 and following the MEDDEV 2.7/1 and MDCG 2020-5 guidance documents.