The document MDCG 2020-5 (“Clinical Evaluation – Equivalence”) increases the requirements for the equivalence of medical devices that manufacturers can refer to in the clinical evaluation of their device.
A clear understanding of the regulatory requirements will help you:
This will help you avoid unnecessary iterations and costs and create the conditions required for a quick authorization of your device.
it has the same characteristics. It is precisely this equivalence that manufacturers have to demonstrate in the clinical evaluation. Otherwise, they cannot use the clinical data from the other device to demonstrate the safety, performance and clinical benefit of their own device.
This requirement is included in the definition of the term “clinical data”:
‘clinical data’ means information concerning safety or performance that is generated from the use of a device and is sourced from the following: […] reports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated,
Source: MDR Article 2
The second section describes the MDR's requirements for technical, biological and medical equivalence in more detail.
Read more on clinical data and clinical evaluations.
The manufacturer has to have data that support the claims in the clinical evaluation.
“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.”
Source: MDR Annex XIV Part A (3)
The MDRestablishes additional requirements for specific device classes. These limit the number of manufacturers and devices that can be included in a clinical evaluation based on the equivalence route (i.e. without a clinical investigation):
Class IIb implantable and class III
Predecessor device with modifications with CE-marked predecessor device
Class IIb implantable and class III
Full access to technical documentation regulated by contract
Device without intended medical purpose
Justification when existing clinical data from an analogous medical device is used
Access to pre-clinical and clinical data
Revision four of the MEDDEV 2.7/1 guideline contains a two-page annex, “A1”, that specifies more precisely the conditions under which clinical, technical and biological equivalence may be assumed to exist.
Section 2 below gives a more detailed overview of these requirements.
The MEDDEV document contains additional requirements.
Read more on the topic of MEDDEV 2.7/1 Revision 4.
Manufacturers may be tempted to use a different comparator device for each aspect of equivalence (technical, biological, clinical – see Fig. 1). This is exactly what MEDDEV 2.7/1 rules out.
Manufacturers can only use a device’s clinical data if the device is equivalent in all three aspects (see Fig. 2). Otherwise, it does not count as an equivalent device.
However, manufacturers can use data from more than one equivalent device if they are all equivalent in all three aspects.
MEDDEV also requires manufacturers to disclose all the differences between their own device and the device they are claiming is an equivalent device. The guideline expects explanations why these differences do not significantly affect clinical performance and the clinical safety.
The requirement that only clinical data from CE-marked medical devices can be used in clinical evaluations has led to a lot of discussion.
When reviewing the technical documentation, notified bodies generally no longer insist on this requirement and also accept, for example, devices that have been authorized in the USA as equivalent devices.
The MDCG document is actually aimed at notified bodies. However, because it explains the requirements of the MDR and MEDDEV 2.7/1, manufacturers should also take a look at this MDCG guideline.
The requirements of the MDR and MEDDEV are not exactly the same. In some cases, the MEDDEV requirements go beyond those of the MDR, and in other cases the MDR contains requirements that the MEDDEV document does not.
For example, if the devices are technically equivalent, the MDR requires the software algorithms be considered. The MEDDEV document does not address this. The MDCG-2020-5 guideline repeatedly emphasizes the relevance of these software algorithms, unless the software does not have a medical purpose but, for example, only controls the hardware.
According to MDCG 2020-5, the requirement for the software algorithms to be equivalent does not extend to the equivalence of the software code itself. “Only” the functional principle, the clinical performance(s) and the intended purpose(s) of the software algorithm are relevant.
However, the guideline insists that the code must have been developed in line with international standards, such as IEC 62304. Whether this is referring to the code of the manufacturer’s device or of the equivalent device is not clear. If it is the manufacturer's device, this would be a regulatory requirement in any case.
A lot of manufacturers confuse equivalent and similar devices when preparing their clinical evaluation. The MDCG 2020-5 guideline warns against precisely that. The MDCG defines similar devices as follows:
“The term ‘similar devices’ may be understood as devices belonging to the same generic device group. The MDR defines this as a set of devices having the same or similar intended purposes or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics.”
Source: MDCG 2020-5, section 5
As similar devices are not compared on the basis of specific characteristics, manufacturers cannot use them for the equivalence assessment.
However, data from similar devices can be useful for a variety of other purposes. The “Tips” section provides further information.
The MDCG 2020-5 document wants manufacturers to document the comparisons for technical, biological and clinical equivalence in a table. As a result, the guideline provides tables containing the attributes to be compared (see Fig. 4). The second section looks at these attributes (characteristics).
MDCG 2020-05 expects evidence for each characteristic. This evidence must be based on valid scientific data, such as:
These pre-clinical and clinical data from the equivalent device must relate to a defined generation or version of the device.
The MDR defines the criteria for clinical equivalence:
“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.”
Source: MDR Annex XIV Part A (3)
That means that your own device and the equivalent device must be used:
Otherwise, the “equivalence route” cannot be used for the clinical evaluation.
Comparing these attributes in a table is recommended:
Clinical condition or purpose
Patient population: Age
18 years and older
Patient population: Disease (severity, stage)
Physicians, intensive care staff
Performance in terms of expected clinical effect
According to the MDCG-5 document, a user means any healthcare professional or lay person who uses a device.
A lay person can be an individual who does not have formal education in a relevant field of healthcare or a medical discipline.
You must therefore take into consideration whether the intended user’s competence or knowledge could have an effect on the safety, clinical performance and desired clinical outcome.
The equivalent device should be intended for use under the same clinical conditions or for the same purpose, including for similar severities and stages of disease.
The MDR does not explicitly require the same patient population, but it does require a scientific justification as to why relevant aspects do not play a significant role with regard to clinical performance, safety and benefits of the device.
For this, the following aspects should be considered in the clinical evaluation:
However, the devices must be used at the same site in the body.
The equivalent device must also have a similar relevant critical performance in view of the expected clinical effect for a specific intended have purpose.
The MDR defines the criteria for biological equivalence:
“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;”
Source: MDR Annex XIV Part A (3)
This means that the equivalence route is only possible if your device and the equivalent device are made of the same materials or substances in contact with the same human tissues or body fluids. Otherwise, this is the end of the equivalence route.
Tables are also recommended here to compare the attributes:
Materials and substances
A, B and C
B, C and D
Not the same (end)
Contact with human tissue or body fluids
A and B, not C
Not the same
Type and duration of contact
2 h, direct skin contact
Undefined, direct skin contact
Release characteristics of substances, degradation products, leachables
The distinction between the same materials or substances and similar release characteristics of substances is only made because the processing, design and use environment can influence the release characteristics of the material. Even when the raw materials are the same.
Processing can also make materials more susceptible to degradation. For example, small changes in pH or oxidative stress can increase or decrease such release. For this reason, it is the final device that should always be tested.
The equivalence comparison is even more demanding for devices made of substances or combinations of substances or even ones that contain medicinal products.
“Substances” and “combinations of substances” also refer to all associated ancillary substances and coatings. In this case, manufacturers have to review additional characteristics for the clinical evaluation, such as:
The MDCG guideline refers to the ISO 10993 series of standards.
Read more on biocompatibility and ISO 10993.
MEDDEV 2.7/1 allows manufacturers to make exceptions if their own device and the comparator device do not use the same substances or materials. The MDCG 2020-05 guideline points out that these exemptions are no longer permitted under the MDR.
According to the MDR, the technical equivalence only has to be a similarity, but there are limits here as well.
“The device is of similar design; is used under similar conditions 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;”
Source: MDR Annex XIV Part A (3)
An equivalence table should, for example, compare the following attributes of the two devices:
Conditions of use
Specifications and physicochemical properties
Principles of operation
The conditions of use must be similar to the extent that there are no clinically significant differences in safety and clinical performance between your device and the equivalent device. The conditions of use include the physical environment (e.g., brightness, moisture, vibrations, contamination, temperature and pressure).
For the specifications and physicochemical properties, manufacturers should consider the following:
The software is considered one of the principles of operation. We already looked at this aspect in section 1.c).
Technical equivalence only requires similarity for a lot of characteristics. However, these differences must be scientifically justified.
Manufacturers rarely have access to the technical document for competitors’ devices. If data required to demonstrate equivalence for some attributes is missing, it may be helpful to generate this data through comparative testing.
If these tests also fail to provide sufficient evidence or conformity, a clinical investigation becomes more likely. Manufacturers should then be careful to specify what evidence they want to use. The endpoints of the clinical investigation should be defined and the study protocols designed with this evidence in mind.
Manufacturers cannot use (clinical) data from devices that are similar but not equivalent to demonstrate safety, performance and clinical efficacy. But this data can still be useful for a variety of other purposes:
The MDCG 2020-5 guideline is aimed at notified bodies. Medical device manufacturers would also be well advised to study this document:
However, it is worth thinking about why a document like MDCG 2020-5 is needed:
It is clear that the requirements for the equivalence of devices and therefore the clinical evaluation as a whole must be strict. After all, manufacturers have to conclusively demonstrate that their devices are safe, perform as intended and really are beneficial to patients.
But disproportionately high requirements also prevent beneficial devices being authorized and mean avoidable costs for manufacturers. The MDCG has intensified this problem with its 2020-5 document.
The Johner Institute’s team of clinical evaluators has prepared countless clinical evaluations in compliance with the requirements of the MDR, MEDDEV 2.7/1 and MDCG 2020-5 and has safely guided them through review by notified bodies.