In the first blog post after the summer break, we include the new MDCG documents, which specifically concern clinical trials with medical devices. In this article we present both documents and address the points that may be of concern to sponsors and therefore also manufacturers.


CE Marking on a product to signify that it meets the legal requirements to be sold on the extended Single Market in the European Economic Area (EEA).

CIP Clinical investigation plan

DMIDS German medical device information and database system

EUDAMED European database on medical devices

GSLA Basic Security and Performance Requirements

IVDR Regulation (Eu) 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices

MDCG Medical Device Coordination Group

MDR Medical Device Regulation; EU Regulation 2017/745

MPI Medical Device Information System

MS Member State

NCA National Competent Authority

PMCF Post-market clinical follow-up

REC Research ethics committee

Underlying regulations

EU Regulation 2017/745 (MDR)
MDCG 2021-6
MDCG 2021-8

1 Introduction

The Medical Device Coordination Group (MDCG) regularly and continuously publishes so-called guidance documents for the MDR. This is done in accordance with Article 105 of the MDR and Article 99 of the IVDR. The documents are prepared in collaboration with interested parties represented in the various groups and are given in the following format: "MDCG Year Number Revision".

The MDCG is composed of representatives from all Member States and is chaired by a representative of the European Commission. The documents are not European Commission documents and cannot be regarded as the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give a binding interpretation of Union law.

They simply represent a common view on how the MDR and the IVDR should be applied in practice in order to achieve an effective and harmonized implementation of the legislation.

This article now deals with the two newly published MDCG documents 2021-6 and 2021-8.

MDCG 2021-6 is aimed at sponsors of clinical trials of medical devices that are carried out within the scope of Regulation (EU) 2017/745 (MDR). It covers questions and answers and may be supplemented with further questions and answers in due course.

The document MDCG 2021-8 “Clinical investigation application/notification documents”, on the other hand, addresses the documents to be submitted when applying for a clinical trial.

2. New MDCG documents

2.1 MDCG 2021-6

This MDCG document, published last April, contains a total of 28 general questions and related answers:

On the one hand, the differences between the MDR and the previous Directive 93/42/EEC are discussed:

What are the general differences and improvements related to clinical investigations under the new Regulation (EU) 2017/745 (MDR) as compared to the Directives 93/42/EEC and 90/385/EEC?

Basically there is none here, except that the MDR represents a different, more binding set of rules that is intended to ensure a more uniform and predictable feasibility of clinical trials.

In addition to the definition of the clinical trial, which was taken from the MDR (question 2), the third question is interesting again:

What is the difference between the performance, clinical performance and clinical benefit?

According to the MDR, the performance (definition see Article 2(22) of the MDR) of a product is the ability of the product to fulfill its intended purpose as specified by the manufacturer. In a broader sense, the clinical performance (definition see Article 2(52) of the MDR) of a medical device is the ability of the product to fulfill its intended purpose and thereby provide a clinical benefit when used as intended (definition see Article 2(53) of the MDR) to provide. Clinical benefit is the positive impact of a product on a person's health, expressed in the form of a meaningful, measurable, patient-relevant clinical outcome (including diagnostic-related outcomes) or a positive impact on patient management or public health.

Fig. 1 Definition of performance, clinical performance and clinical benefit.

Until now, a distinction has never been made so precisely between performance (to fulfill the intended purpose) and clinical performance (performance to provide the clinical benefit, i.e. the clinical aspects of the service).

But this is important, not only with regard to clinical trials when choosing the primary and secondary endpoints, but also when defining the claims about clinical performance within the framework of the clinical evaluation.

The ninth question covers the subject of “additional incriminating investigations” and defines these in accordance with Article 74.

“Additional procedures that are stressful may include a variety of different procedures, including procedures that may cause pain, discomfort, anxiety, potential risks or complications/side effects, disruption to life and personal activities, or other unpleasant experiences. It is usually determined from the perspective of the person bearing the burden.

Other invasive procedures include penetration into the interior of the body through the body surface, including through the mucous membranes of body openings, or penetration into a body cavity through a body opening.”

These include, for example, blood samples or biopsies that are also carried out as part of the clinical trial and are not part of routine clinical practice.

However, there is still uncertainty here and it is advisable to contact the ethics committee and also the authorities as part of the respective clinical trial in order to be able to make the right decision regarding the application if there are any controversial questions regarding the additional burden.

Overall, many questions concern the correct regulatory path that must be followed in the respective constellation of the medical device with regard to a clinical trial. This is about Articles 62, 74 and 82 of the MDR. We would be happy to provide individual advice on this as part of our free initial consultation .

From question 15 up to and including question 20, changes to the clinical trial plan (amendments) are discussed and questions 21 to 28 deal with deadlines and transition periods.

As a basic overview, this MDCG document is certainly suitable for briefly addressing fundamental questions. However, detailed information or explanations cannot be found and must be clarified as part of the consultation in relation to the individual case.

2.2 MDCG 2021-8

A clinical trial, except in the case of a PMCF clinical trial not covered by Article 74 of the MDR, must be submitted with an application containing the documents referred to in Chapter II of Annex

Since the European Medical Devices Database (EUDAMED) does not yet exist, the MDCG has now created a series of clinical trial application/notification documents to support the clinical trial procedures under the MDR.

Attention: In Germany, clinical trials are applied for via the medical device information system, now the German Medical Device Information and Database System ( DMIDS ), at BfArM (formerly DIMDI ), which already contains the templates listed in the MDCG document as queries.

These documents include:

  • Clinical examination - application/reporting form within the framework of the MDR
  • Addendum to the application/reporting form for clinical trials for:
    • Additional test product(s) (Section 3)
    • Additional comparator(s) (Section 4)
    • Additional testing body(s) (Section 5)
  • Supporting documents for the clinical trial - Appendix of documents to be attached
  • Checklist of general safety and performance requirements, standards, common specifications and scientific recommendations

As far as possible, the clinical trial application/notification form contains the same data fields as the EUDAMED system, which is still under development.

The templates are listed in the MDCG document and can be accessed via the following links:

Clinical investigation – application form under Medical Device Regulation


Additional investigational device(s) (section 3)

Additional comparator device(s) (section 4)

Additional investigation site(s) (section 5)


This document also contains a link to a list of the required documents, which is based on ISO 14155:2020.

Finally, you receive a template for the checklist of the basic safety and performance requirements (GSLA), standards, common specifications, etc., which is based on the MDR checklist:

Fig. 2 List of standards, CS and scientific references, except those examined in the clinical trial

Fig. 3 Matrix for fulfilling the GSLA

Apart from the two Word templates, this MDCG document does not provide any new information for clinical trials carried out in Germany, as everything can be entered and applied for via the DMIDS.

3. What we can do for you

We act as a scientific, manufacturer-independent institution (CRO). As such, we support you throughout your entire clinical trial project - from the initial idea to the evaluation and the clinical trial report.

4. How we can help you

At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.

Do you already have some initial questions?

You can get a free initial consultation here: free initial consultation 

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