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. The second part dealt with the application process for clinical trials with CE-marked products. Today's third part is about the application process for other clinical trials.
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 3: Application procedure - approval process for other clinical trials - Article 82 MDR
1 Introduction
Currently and until the MDR comes into effect on May 21, 2021, the topic of “other clinical trials” is not regulated. And this despite the fact that basic research has not only existed since EU Regulation 2017/745 (Medical Device Regulation, MDR) in 2017. But clinical trials in the context of basic human research that are not carried out to assess clinical performance, safety and benefit often led to uncertainty among the respective ethics committees and to some projects that could not be implemented.
All of this is changing with the MDR:
The MDR now regulates this in Article 82 with the so-called “other clinical investigations”, whose implementation at the national level in Germany via the MPEUAnpG (Medical Devices EU Adaptation Act) in Chapter 4, Subsection 2 , § 47 to § 61 is detailed. This also includes the application and approval procedures for this type of clinical trial, which can be carried out with a product in development, with a prototype or with CE-marked products. This depends on when the scientific or other question needs to be answered.
2. Approval process for other clinical trials with medical devices (Article 82 MDR and MPEUAnpG § 47-53)
2.1 Definition: Section 3 Sentence 4 of the MPEUAnpG
An “other clinical trial” of a product is a clinical trial that
a) is not part of a systematic and planned product development process or product observation of a current or future manufacturer,
b) is not carried out with the aim of demonstrating the conformity of a product with the requirements of Regulation (EU) 2017/745,
c) serves to answer scientific or other questions and
d) takes place outside of a clinical development plan in accordance with Annex XIV Part A Number 1 Letter a of Regulation (EU) 2017/745.
“Other clinical trials” are therefore NOT used to demonstrate performance, safety and benefits in accordance with Article 62 Section 1 MDR. They are therefore not to be equated with clinical trials as part of the conformity assessment procedure (Article 62 Para. 1 of the MDR) or with clinical trials in relation to products that bear the CE marking (Article 74 of the MDR) and thus PMCF studies!
In principle, however, it also applies to “other clinical trials” that the test product must meet the basic safety and performance requirements and be safe (Section 62 Paragraph 4, Letter l).
The “other KP” must comply with Section 62 MDR paragraphs 2, 3 and 4 letters b, c, d, f, h and l and paragraph 6.
Who will check this now?
2.2 Which applications must be submitted?
In order to check whether products/prototypes with which the other clinical trial is to be carried out are safe and meet the above requirements, the following must be observed:
- The requirements for other KP are regulated in Sections 47ff MPEUAnpG and described in the corresponding blog post from November (Other clinical trials with medical devices).
- Here too, an approving EC statement is required (= EC vote).
- According to Section 53 of the MPEUAnpG, a report to BfArM is now also required:
“According to Section 47 Paragraph 2 Number 2, any other clinical trial must be reported by the sponsor to the responsible higher federal authority via the German Medical Device Information and Database System in accordance with Section 86.”
- Changes must also be reported (Section 54 MPEUAnpG).
The deadlines for the EC statement are the same as for clinical trials according to Article 62 Para. 1 of the MDR (Part 1 of the Christmas special).
Informed regarding the report to BfArM
the Federal Institute for Drugs and Medical Devices [...] via an automated process, the authority responsible for the sponsor's registered office or the registered office of its legal representative and the authorities responsible for the testing centers via a notification.
So there is only information, but no assessment/approval etc. takes place.
Subsection 2 - Title 1 - Section 47 Paragraph 3 of the MPEUAnpG defines the procedure for other clinical trials with products that already bear the CE marking in accordance with Article 20 Paragraph 1 of Regulation (EU) 2017/745, insofar as the other clinical trial is carried out within the scope of the intended purpose covered by the CE marking and the test subjects are not subjected to any additional invasive or stressful procedures beyond the normal conditions of use of the product.
- In this case, no opinion from the ethics committee is required.
- A report to the higher federal authority does not have to be made either.
2.3 What does this mean?
For other clinical trials with prototypes, medical devices in development (without the CE mark) or with their components, a statement from the EC is required as with an approval study (see part 1 of the Christmas special). This means that once the MDR is valid, an EC vote is definitely required for other clinical trials. (Article 62 paragraph 4 sentence b) This other clinical trial must be reported to BfArM (Section 47 MPEUAnpG).
For CE-marked products, neither an EC vote nor a notification to BfArM is required for other clinical tests to answer scientific or other questions.
But be careful : If additional invasive or stressful procedures are used as part of the other clinical trial or if the medical device is used outside of its intended purpose, the sponsor must report the other clinical trial to BfArM and obtain a statement from the EC.
2.4 What effects does this have?
The EC vote required for other clinical trials with non-CE-marked medical devices means a full examination of the qualifications of the main investigator and examiner: The MDR itself says nothing about this; these requirements arise from the national regulations in Section 30 of the MPEUAnpG:
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 two years of experience with medical device studies is also required as a qualification requirement for other clinical trials that require an EC vote. This therefore also represents a major hurdle for these clinical trials from May 2021.
3. Outlook
That was part 3 of our “ Christmas Special ” and this week there will be another article on safety reporting in clinical trials, which is regulated in detail in the guidance document MDCG 2020-10/1. 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 this campaign is that the contribution will continue to grow with part 4 this week until Christmas.
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