The clinical trial types blog series will be interrupted by our “Christmas Special” in December. We would like to inform you comprehensively about the important changes to clinical trials due to the MDR this year so that you are prepared for 2021.
The special thing about our campaign is that the contribution grows until Christmas. New sections are added every week. The topic of DiGA studies will continue in January.
The first part of our December special provided a guide to the application process for clinical trials within the framework of the conformity assessment procedure at the Federal Institute for Drugs and Medical Devices and the ethics committees. Today's second part deals with the application process for clinical trials with CE-marked products.
Abbreviations.
BOB (higher federal authority)
EK (Ethics Commission)
KP (clinical examination)
MDR (medical device regulation; Regulation 2017/745)
MPEUAnpG (the Medical Devices EU Adaptation Act was passed as law by the Bundestag on May 25, 2020. This MPAnpG-EU describes the Medical Devices Implementation Act (MPDG) in Article 1)
MPDG (the MPDG will gradually replace the Medical Devices Act (MPG) from May 26, 2021 and will be legally binding for all manufacturers and operators of medical devices in Germany).
Part 2: Application procedure – Approval process for clinical trials with CE-marked products – Article 74 MDR
1 Introduction
Currently, and until the MDR comes into effect on May 21, 2021, Sections 20 et seq. of the German Medical Devices Act (MPG) apply to the authorization of clinical trials conducted in Germany. For clinical trials with CE-marked products, the "exception" to clinical trials under Section 20 MPG is found in Section 23b MPG. This covers so-called PMCF studies. The MEDDEV Guideline for Post-Market Clinical Follow-up Studies (MEDDEV 2.12/2 Rev. 2), which is subordinate to the MPG, also applies. This means that only an application for professional ethics consultation needs to be submitted to the ethics committee responsible for the study center and the investigator, in accordance with Section 15 of the Professional Code of Conduct for Physicians (BO), and the ethics committee does not issue a formal opinion. However, this only applies if the product is used within the scope of this clinical trial in accordance with its intended purpose and/or no additional burdensome examinations are conducted. If this is the case, Section 20 of the Medical Devices Act (MPG) applies again. This is also illustrated in the two following figures:
Figure 1: Previous approval process before CE marking (changes due to the MDR articles)
Figure 2: Previous approval process after CE marking (changes due to the MDR articles)
All of this is changing with the MDR, as it describes and defines the approval process, and the associated MPDG (Medical Devices Act) outlines the national procedure for ethics committees. The relevant articles of the MDR are already listed in both figures above. For example, Section 23b of the MPG (Medical Devices Act) is being completely eliminated. This is one of the most significant changes and consequences of the MDR, as the professional consultation provided by the ethics committee is no longer required. The following section describes what needs to be considered in this regard from May 2021 onwards.
2. Approval process for clinical trials with CE-marked products - Article 74 MDR
For so-called "PMCF studies" (post-market follow-up = clinical follow-up after the product has been placed on the market), a distinction is made between whether the investigational product is used within its intended purpose or not. Previously, Section 23b of the German Medical Devices Act (MPG) and Section 7 of the German Medical Devices Clinical Trials Ordinance (MPKPV) applied. Neither of these was incorporated into the German Medical Devices Adaptation Act (MPAnpG) (which only regulates the national application procedure to the European Commission), but rather covered by the Medical Device Regulation (MDR)
2.1 The medical device bearing the CE mark is used within the scope of its intended purpose
The following articles of the MDR apply:
- Article 74 paragraph 1 and
- then the rules of Section 62 Paragraph 4, letters b to k and m apply,
- Articles 75 to 77, Article 80 paragraph 5 (vigilance) and
- the provisions of Annex XV of the MDR and here the required documents from Chapter II
What does that mean?
An opinion from the Ethics Committee (EC) is required, as is the case for a registration study (see Part 1 of the Christmas Special). This means that with the MDR's entry into force, an EC opinion will also be required for PMCF studies. (Article 62, paragraph 4, sentence b)
Under these conditions, an application to the BOB is still not required.
Attention : If additional invasive or burdensome procedures are used within the PCMF study, the sponsor must inform the BfArM (Federal Institute for Drugs and Medical Devices) at least 30 days before the start of the clinical trial and submit the documents in accordance with Annex XV, Chapter II. Previously, this was regulated by Section 23b of the German Medical Devices Act (MPG) in conjunction with Section 7 of the German Medical Devices Clinical Trials Ordinance (MPKPV), and the BfArM only conducted a less comprehensive review, particularly with regard to the safety aspects of the additional burdensome examination.
In this case, as above, an EC vote is required, but the documents must also be submitted to BfArM via EUDAMED
What does that mean?
As above, a vote from the EC is still required, and in addition, an application must now also be submitted to BfArM via EUDAMED.
The application deadlines are the same as for clinical trials under the conformity assessment procedure (see Part 1).
What are the implications of this?
The change towards EC approval for PMCF studies means a full review of the qualifications of the principal investigator and the investigator: The MDR states in Article 62, paragraph 4, sentence j:
The responsibility for the medical care of the trial participants lies with a physician with appropriate qualifications or, where appropriate, a qualified dentist or any other person authorized under national law to provide the corresponding patient care within the framework of a clinical trial...
And this is further detailed nationally in § 30 of the MPAnpG:
those who can demonstrate at least two years of experience in the clinical testing of medical devices can be appointed as head of a clinical trial or other clinical trial .
(5) Proof of the required qualifications must be provided through a current CV and other meaningful documents.
This means that in the future, two years of experience with medical device studies will also be required as a qualification for PMCF studies. Since this was not required within the framework of the professional guidance provided by the European Commission (EC) according to Section 23b of the German Medical Devices Act (MPG) and Section 15 of the Professional Code of Conduct (BO), this will represent a greater hurdle for conducting PMCF studies from May 2021 onwards.
2.2 The medical device with CE marking is used outside its intended purpose
If the CE-marked product is used outside its intended purpose within the scope of a study (e.g., to collect clinical data for a new indication), Articles 62 to 81 apply, just as they would for a registration study. Previously, this was also regulated by Section 23b of the German Medical Devices Act (MPG) in conjunction with Section 7 of the German Medical Devices Clinical Trials Ordinance (MPKPV), and the Federal Institute for Drugs and Medical Devices (BfArM) only conducted a less extensive review, particularly regarding the safety aspects of the extended intended purpose. This now changes under the Medical Device Regulation (MDR), and the following regulations therefore apply::
- Articles 62 to 81, i.e., as in a registration study (Part 1 of the Christmas special)
- Appendix XV and here documents from Chapter II
A statement from the European Commission (EC) is required, as with a clinical trial (see Part 1 of the Christmas Special). Furthermore, as with clinical trials, an application must be submitted to the Federal Institute for Drugs and Medical Devices (BfArM) (via EUDAMED).
The application deadlines are the same here as for clinical trials within the framework of the conformity assessment procedure (see Part 1).
3. Outlook
This concludes part 2 of our " Christmas Special, " and next week we'll continue with the approval process for other clinical trials. We will again provide you with comprehensive information on the important changes to clinical trials brought about by the MDR this year, so you are prepared for 2021.
The special thing about our campaign is that the contribution grows until Christmas. New sections with further changes are added every week.
DiGA studies will continue in January.
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