Detailed, clear – in short: everything at a glance. Latest recommendations of the Medical Device Coordination Group (MDCG) regarding the equivalence assessment of medical devices in comparison of MDR and MEDDEV 2.7/1Rev. 4 in connection with prerequisites, concrete actions and evaluation.
Does each egg resemble the other? In the specific case, MDCG 2020-5 “Clinical Evaluation – Equivalence: A guide for manufacturers and notified bodies” deals with the prerequisites for and the concrete design of the equivalence consideration in the context of the preparation of clinical evaluations. Generally speaking, the equivalence assessment should be carried out according to the valid rules of the MDR; the specifications and recommendations of MEDDEV 2.7/1 Rev. 4 continue to be justified in this framework, but there are nevertheless deviations from the MDR, which are discussed in the MDCG-2020-5 document without introducing new aspects and specifications. Only the MDR remains legally binding.
In the same wording as the MDR, the MEDDEV 2.7/1 Rev.4 requires that technical, biological and clinical characteristics must be considered in the assessment of equivalence when preparing a clinical evaluation based on the equivalence principle. Differences between MDR and MEDDEV 2.7/1 Rev. 4 are evident in the criteria for evaluating these three characteristics, which the MDCG 2020-5 document addresses.
Technical aspects
While the MEDDEV 2.7/1 Rev. 4 requires that the medical device to be evaluated and the equivalent product must be used under the same conditions of use with regard to technical characteristics, the MDR only mentions similar conditions of use. If, according to MDCG 2020-5, no clinically significant difference in safety and performance is to be expected, the conditions of use are to be assessed as similar.
MDCG 2020-5 further indicates that the MDR singles out the aspect of software algorithms (in contrast to MEDDEV 2.7/1 Rev. 4), both for software that is necessary for the operation of a medical device and for software that is itself classified as a medical device in its own right. According to MDCG 2020-5, in order to be able to demonstrate and evaluate equivalence in the sense of the MDR, in this case both the functional principle of the software – or more precisely of the underlying algorithm – and the clinical performance as well as the defined intended purpose must be included in the consideration.
Biological aspects
While the introductory sentence is still largely congruent between MDR and MEDDEV 2.7/1 Rev. 4 (“use of the same materials or substances in contact with the same type of human tissue or body fluids”), crucial differences subsequently arise that tighten the biological equivalence comparison in MDR:
The exceptions mentioned in MEDDEV 2.7/1 Rev. 4 when assessing equivalence with regard to medical devices that only have contact with intact skin areas, or for individual components of the medical device that are only of secondary importance, no longer apply in the course of the MDR. The approach of being able to rely in these cases on the results of the risk analysis regarding these materials, based on the biological properties and the corresponding use and thus postulated similarity, is no longer permissible in the legal framework of the MDR. MDCG 2020-5 explicitly points this out.
In addition to the introductory sentence above, the MDR also requires at least a similar period of use and a similar release mechanism of substances used; this includes degradation products and leachables to demonstrate biological equivalence. MDCG 2020-5 provides background information on this point, stating that this formulation is intended to account for the fact that changes may occur due to external influences or processing of certain substances or materials, even if the raw materials used are identical.
For medical devices that are composed of several substances or represent a combination of substances and are absorbed or dissolved in the human body, the same substances must also be used in order to demonstrate equivalence. Although these products are not medicinal products, MDCG 2020-5 indicates that compliance with the relevant requirements of Annex 1 of Directive 2001/83/EC must still be considered in order to claim biological equivalence under the MDR.
Clinical aspects
MDCG 2020-5 describes two aspects with regard to clinical equivalence, which in terms of wording and meaning paint a different picture to MEDDEV 2.7/1 Rev. 4:
Both the medical device to be evaluated and the equivalent product must be used or applied by the same user group; from the point of view of the MDR, it is irrelevant whether this is a healthcare professional or a layperson without prior medical training. Ultimately, this requirement represents a tightening of the specifications compared to MEDDEV 2.7/1 Rev. 4.
While the MEDDEV 2.7/1 Rev. 4, with regard to clinical use, clearly talks about the fact that the medical devices to be compared must be used for the same medical indication as well as for the same gender and duration of use, the MDR formally describes this in a weakened form with “same clinical condition of the patient or for the same purpose”. However, the interpretation within the MDCG 2020-5 document concludes that this aspect is equivalent to the same level in terms of equivalence comparison as in the MEDDEV 2.7/1 Rev. 4, despite the different wording.
According to MDCG 2020-5, the global establishment of the equivalence comparison is primarily a matter of demonstrably and justifiably demonstrating all the characteristics of a technical, biological, and clinical nature required and listed in the MDR in order to conclude that there is no clinically significant difference in safety and clinical performance from the equivalent product. It is still not exempt to map multiple equivalence products in the clinical evaluation, but each of these products must meet the MDR requirements in the three categories listed above. A combination of features of different products is not permitted, as was already the case in MEDDEV 2.7/1 Rev. 4.
Furthermore, as part of its assessment of the MDR, MDCG 2020-5 points out that differences of a technical, biological or clinical nature that arise in the equivalence comparison can be conclusively evaluated on the basis of scientific evidence and ideally assessed as not clinically significant. Preclinical data, in turn, can be very helpful, especially when considering technical and biological equivalence characteristics. These must, of course, relate to the current version/generation of the medical device under consideration.
MDCG 2020-5 also addresses the limits of the fundamental admissibility of the equivalence procedure. This concerns manufacturers of class 3 devices as well as implantable devices. The equivalence approach is only permissible at all in the following two case constellations, regardless of the content of the equivalence approach:
The manufacturer refers to a predecessor product from his own company, which is already CE-approved and marketed in accordance with the MDR or 93/42/EEC or 90/385/EEC directives.
The manufacturer refers to an equivalent product of a competitor with whom a contractual basis exists that allows unrestricted and continuous access to the technical documentation of this equivalent product. In addition, there must be access to the clinical evaluation, performed in accordance with the MDR, which implies that this medical device has already been certified under the MDR.
In all other cases, the demonstration of safety and clinical performance will only be able to take place on the basis of clinical investigations.
For devices without a medical use as defined in Annex XVI of the MDR, such as contact lenses or devices for transcranial stimulation of the brain, clinical investigations should in principle be performed, unless clinical data of an analogous medical device are available. Analog means product with similar technical basis and risk profile, but with medical intended use. Thus, in a large number of cases, even for relatively trivial products, the performance of a clinical trial is to be expected, since possible equivalent products cannot be identified or can only be identified with difficulty.
In addition to one of the central elements, the demonstration of equivalence (if the clinical evaluation is based on this principle), it is also important in the clinical evaluation to identify relevant hazards or clinical risks, to describe the state of the art, alternative treatment methods and the clinical background of the underlying disease in a scientifically sound manner. The basis for this can be provided by scientific publications of similar medical devices that belong to the same generic product group as the medical device to be evaluated.
Finally, a note on the identification of appropriate clinical data: For both the medical device being evaluated and the equivalent device, all available data should be used, regardless of whether they provide favorable or unfavorable results with respect to the safety and clinical performance of the medical device. The analysis of the data is ultimately directed toward matching or establishing compliance of the clinical evidence with the relevant, essential safety and performance requirements. The procedure for identifying, evaluating and analyzing clinical data can still be found in MEDDEV 2.7/1 Rev. 4; these rules continue to apply under the MDR, provided that the clinical data meet the MDR definition, see Article 2, item 48 of the MDR.
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