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 gave you a guide to the application process for clinical trials as part of the conformity assessment procedure with the higher federal authority 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 is valid from May 21, 2021, Sections 20 ff MPG currently apply to the approval of clinical trials for clinical trials carried out in Germany. For clinical trials with CE-marked products, the “exception” to clinical trials according to Section 20 MPG can be found in Section 23b MPG. This covers the 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 to this. This means that only an application for professional advice must be submitted to the ethics committee responsible for the test center and the examiner in accordance with Section 15 BO (professional regulations for doctors) and the ethics committee (EK) does not give a vote. However, this only applies if the product is used within the scope of this clinical trial for its intended purpose and/or no additional stressful examinations are carried out. If this is the case, Section 20 MPG applies again. The following two figures also show this:
Figure 1: Previous approval process before CE marking (changes due to the MDR article)
Figure 2: Previous approval process after CE marking (changes due to the MDR article)
All of this is now changing with the MDR, as the approval process and the national procedure for the ECs are described and defined in the associated MPDG. The corresponding articles from the MDR are already listed in both figures above. For example, this disappears B. Section 23b MPG completely. This is one of the biggest changes and effects of the MDR, as professional legal advice from the ethics committee is now no longer required. What needs to be taken into account here from May 2021 is now described below.
2. Approval process for clinical trials with CE marked products - Article 74 MDR
For the so-called “PMCF studies” (post-market follow-up = clinical follow-up after the product has been placed on the market), a distinction is made as to whether the test product is used within its intended purpose or not. So far, the above-mentioned § 23b MPG and § 7 of the MPKPV have been applied here. Neither was included in the MPAnpG (only the national application process at the EC is regulated here), but is covered in the MDR:
2.1 The medical product with 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 § 62 paragraph 4, letters b to k and m apply,
- Articles 75 to 77 Article 80 paragraph 5 (vigilance) as well
- the provisions of Annex XV of the MDR and here the required documents from Chapter II
What does that mean?
A statement is required from the EC as in an approval study (see part 1 of the Christmas special). This means that once the MDR is valid, an EC vote is also required for PMCF studies. (Article 62 paragraph 4 sentence b)
An application to the BOB still does not have to be submitted under these conditions.
Attention : If additional invasive or stressful procedures are used as part of the PCMF study, the sponsor must inform the BOB at least 30 days before the start of the clinical trial and submit the documents in accordance with Annex XV Chapter II. Until now, this was regulated by Section 23b MPG in conjunction with Section 7 of the MPKPV and BfArM only carried out a less extensive review, particularly with regard to the security aspects of the additional onerous investigation.
As above, an EC vote is required here, 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.
In this regard, the application deadlines are the same as for clinical trials as part of the conformity assessment procedure (see Part 1).
What impact does this have?
The change to the EC vote in PMCF studies means a full examination of the qualifications of the main examiner and examiner: The MDR says in Article 62 paragraph 4 sentence j:
the responsibility for the medical care of the subjects shall be a doctor with appropriate qualifications or, where appropriate, a qualified dentist or any other person authorized by national law to provide appropriate patient care in the context of a clinical trial...
And this is detailed nationally in Section 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 requirement for PMCF studies. Since this was not required as part of the EC's professional legal advice in accordance with Section 23b MPG and Section 15 BO, this will also represent a major hurdle for the implementation of PMCF studies from May 2021.
2.2 The medical product with the CE mark is used outside of its intended purpose
If the CE-marked product is used outside of its intended purpose as part of the study (e.g. to collect clinical data for a new indication), Articles 62 to 81 also apply as in the case of a registration study. Until now, this was also regulated via Section 23b MPG in conjunction with Section 7 of the MPKPV and BfArM only carried out a less extensive review, particularly with regard to the security aspects of the extended intended purpose. This is now changing as part of the MDR and therefore applies :
- 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 is required from the EC as in an approval study (see part 1 of the Christmas special). In addition, as with approval studies, an application must be submitted to BfArM (via EUDAMED).
The application deadlines here are also the same as for clinical trials as part of the conformity assessment procedure (see Part 1).
3. Outlook
That was part 2 of our “ Christmas Special ” and next week we will continue with the approval process for other clinical trials. We will once again provide you with comprehensive information about the important changes to clinical trials brought about by 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 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