Established medical devices (so-called legacy devices) are far from obsolete, simply because they were previously only made available under the directives. What must be taken into account so that the products need not / won’t be withdrawn from circulation after the changeover to MDR?
The new guidance, MDCG 2020-6 "Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC", provides guidance to facilitate the identification of clinical data to demonstrate conformity with the essential safety and performance requirements of the MDR, which are required as part of the technical documentation for medical devices already on the market. The term "legacy devices", which is not defined in the MDR but in the present MDCG 2020-6, covers all medical devices that have obtained CE certification under MDD 93/42/EEC or AIMDDD 90/385/EEC. In connection with this, the MDCG 2020-6 provides a definition of characteristics of medical devices with a "well-established technology":
- It is a simple and largely unchanged product design, which is only subject to careful evolutionary steps.
- The generic product group to which the medical device in question belongs is well established in terms of safety aspects; no safety concerns have arisen in the past.
- The clinical performance of the medical device has been proven.
- The associated generic product group represents standard products of medical care without major expected adaptations with regard to indication, intended use or the state of the art.
- The medical devices concerned have been on the market for several years.
Only when all these aspects are fulfilled can one speak of a "well-established technology".
The definition in particular of "legacy devices", which the MDCG 2020-6 provides as a guide for the classification of clinical data, may have a significant impact on whether a manufacturer of class 3 devices or implantable devices can be required to conduct clinical investigations pursuant to Article 61, paragraph 4 of the MDR. Article 61(6a) of the MDR provides that manufacturers of medical devices of the above-mentioned classification are exempted from the obligation to carry out clinical investigations to demonstrate conformity with the essential safety and performance requirements if the medical devices in question "have been lawfully placed on the market or put into service in accordance with Directive 90/385/EEC or Directive 93/42/EEC and their clinical evaluation
- is based on sufficient clinical data, and
- is in conformity with the relevant product-specific specifications for the clinical evaluation of this type of device, where these CS are available'.
The crux of the final assessment of these exemptions is the interpretation of the term 'sufficient clinical data', which is not further specified and defined in the MDR. All in all, according to the interpretation of the MDCG 2020-6, the only statement that can be made is that for both the two guidelines mentioned above as well as for MDR, a quantity and quality of clinical data is required that can represent safety, performance, and a positive risk-benefit ratio; the conclusions derived from this must be scientifically valid.
However, a general definition of "clinical data" can be found in the MDR, Article 2, paragraph 48:
Clinical data means " information concerning safety or performance that is generated from the use of a device and is sourced from the following:
- clinical investigation(s) of the device concerned,
- clinical investigation(s) or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated
- 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,
- clinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up; “
In this context, MDCG 2020-6 points out that "legacy devices" are to be considered within the framework of the legal situation applicable at that time with regard to the original approval and the conformity with GSPRs thus demonstrated, but from the date of validity of the MDR, the requirements of the MDR will apply, in particular for the area of PMCF and PMS. Manufacturers of "legacy devices" should take this into account when considering their product in the clinical context.
Even if the MDR does not provide an explicit definition of "sufficient clinical data", MDCG 2020-6 points out that in the end this is the result of a qualified evaluation which allows the conclusion that the medical devices under consideration are safe and fulfil the intended medical benefit. Furthermore, it emphasizes that this evaluation, like the conduct of the clinical evaluation itself, is an ongoing process.
In order to provide clear guidance for the different phases of clinical evaluation for medical devices already on the market under the MDR (Annex XIV, Part A of the MDR), the MDCG 2020-6 addresses each of these phases:
Phase 0: Clinical evaluation plan and its update
The MDCG 2020-6 notes that in the case of "legacy devices" aspects such as "first-in-man studies, feasibility studies and pilot studies" are not applicable, but the other points mentioned, such as specification of the intended use, indications, contraindications or the target groups on the user side are. Equally important is post-market clinical surveillance, which is fundamental in the context of the MDR, both its detailed planning and its implementation.
Phase 1: Identification of relevant clinical data
Ultimately, all available clinical data must be identified, both for the product itself and for the potential equivalent product. The definition of clinical data is still derived from Article 2, paragraph 48 of the MDR, and the procedure for "legacy devices" is no different from other cases. In particular PMS data from the company's own vigilance system (complaints, incidents), results from PMCF studies or register data can be used as data sources for "legacy devices" when it comes to monitoring the field post-market. In case the medical device in question is based on well-established technologies, data from similar products may also be used.
Phase 2: Assessment of relevant clinical data
There is no difference here compared to the general procedure for the evaluation of clinical data: Determination of the methodological quality of the collected data for the classification of evidence in the overall context of clinical evaluation using verified and validated evaluation tools.
Phase 2a: Generation of new clinical data
The MDCG 2020-6 points out that for products established on the market and being in line with MEDDEV 2.12/2, clinical data from the post-market phase is supposed to be available; however, it may be the case that data are available but do not meet the requirements of the MDR and that collecting clinical data via the equivalence route is no longer possible (see also MDCG 2020-5). Then the generation of new clinical data becomes necessary in order to obtain the CE mark under the MDR.
Phase 3: Analysis of clinical data
Determine whether the clinical data collected and assessed in the previous phases of the clinical evaluation are sufficient to demonstrate conformity with the essential safety and performance requirements. The basis for this determination is the application of quantitative and qualitative analytical methods or the identification of possible gaps in the reasoning or missing data.
The nature of the clinical benefit depends largely on the device itself and its intended use. While direct clinical benefit should be explicitly demonstrated on the basis of clinical data, other sources, such as data from preclinical or benchmark tests, are required to demonstrate indirect clinical benefit.
The combination of the probability of occurrence and the severity of the hazard plays a decisive role in the analysis of the risk; this consideration is carried out in the manufacturer's central risk management system, which must generally be maintained and continuously updated. To this end, the MDR in Annex 1 stipulates that the manufacturer must reduce possible risks as far as possible, including the assessment and estimation of risks that may arise from a foreseeable misuse of the medical device.
With regard to the aspects of risk-benefit assessment, state of the art and alternative treatment methods, the MDCG 2020-6 provides the following "guidance": For the stringent mapping of alternative treatment methods, that are available for almost all "legacy devices" in more or less large numbers, it is of great importance to confine oneself mainly to those ones that comply with the current standard. It does not make sense to rely on alternatives that are no longer in use. In this context, the state of the art and its presentation is of great importance, as it can help to underpin the ranking of alternative treatment methods. However, even with this approach, it should be kept in mind that it is part of the scientific discourse to discuss different opinions and views. Provided they exist, these different opinions and views should be presented and commented on, too. Guidelines of the respective professional societies can always provide assistance in identifying the "true" state of the art, which, depending on the level of evidence, provide more or less valid foundations.
Based on the specifications of the MDR, it is recommended that manufacturers conduct a gap analysis with reference to the clinical data material and collect clinical data in case of gaps in certain areas. A clinical study is a suitable option, but can be very expensive and time-consuming. A systematic review of existing literature, for example, can be an alternative here. If it is not possible to close all gaps, this inevitably entails a critical examination of the claims and intended purpose, but also directly of the indication; all aspects that cannot be substantiated with relevant data must be removed, with all the resulting consequences on the regulatory and above all commercial side. The lack of valid clinical data will be a particular problem for many "legacy devices". The MDCG 2020-6, however, indicates that for products of lower risk classes with a low evolutionary stage, the possibility of continuing to demonstrate compliance with GSPRs even with limited clinical evidence can ultimately be considered - but this must then be verified in each individual case. This also applies to the requirement for PMCF data: Similarly, for "well-established technologies" with no or very low risk, the demand for the collection of clinical data can be made, but here, too, the MDCG 2020-6 points out that the evidence of clinical data must certainly be set lower. It may also be that the results of a well-founded and rigidly implemented PMS system of the manufacturer are sufficient, from which a good clinical picture of the corresponding medical device for safety and performance can be derived based on all recorded complaints and safety reports. For innovative and new technologies, but also for high-risk products, this approach will probably not work, because even if clinical data has been diligently collected in the market phase in the past, it does not necessarily meet the requirements of the MDR, which must then also be examined in each individual case.
Finally, the MDCG 2020-6 provides helpful information on the topics in its annexes:
- The linking of MEDDEV 2.7/1 Rev. 4 with this Guidance Document with regard to further information on actual feasibility
- A possible outline of a clinical evaluation plan covering all relevant requirements of MDR in connection with legacy devices
- An overview of the qualitative ranking of clinical data in the context of demonstrating compliance with GSPRs for legacy devices
When implementing the requirements of the MDR and in relation to the recommendations of the present MDCG Guidance Document, these annexes are an absolute must for manufacturers of "legacy devices". seleon GmbH will be pleased to support you in the evaluation of your established medical devices and their clinical data. So that the tried and tested will also have a place in the future.
Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.