Application for authorisation
Here you will find answers to frequently asked questions about application for authorisation.
What changes are effective as of 21 March 2010?
Since 21 March 2010, in accordance with Section 20 sub-section 1 of the Medical Devices Act (MPG), clinical investigations of medical devices may only be commenced in Germany if the responsible Ethics Committee has issued a favourable opinion on the clinical investigation pursuant to Section 22 MPG and the competent federal higher authority has authorised it pursuant to Section 22a MPG. This approval procedure with the federal higher authority replaces the previous notification obligation with the authorities of the "Land". The beginning of the clinical investigation is specified as the time when the first subject has legally consented to the participation after all the prerequisites for the start of the clinical investigation have been met.
The commencement, duration, changes, completion or early termination of the clinical investigation are regulated in Sections 22a - 23a MPG.
How are applications for approval of a clinical investigation (MDR) or performance study (IVDR) submitted?
Clinical investigation:
The authorisation required under Article 62 (4) a) MDR must be applied for by the sponsor to the competent higher federal authority, here: BfArM. In accordance with Article 70 (1) MDR, the application must be submitted by way of data transmission via the DMIDS central registration system. The application must be accompanied by the documents listed in Annex XV Chapter II MDR. The application form asks for the data that are absolutely necessary for processing the application. Required documents can also be uploaded and transmitted via the system.
Performance study:
The authorisation required under Article 58 (1) or (2) IVDR must be applied for by the sponsor to the competent higher federal authority. In accordance with Article 66 (1) IVDR, the application must be submitted by means of data transmission via the DMIDS central registration system. The application must be accompanied by the documents listed in sections 2 and 3 of Annex XIII and in Annex XIV IVDR. The application form asks for the data that are absolutely necessary for processing the application. Required documents can also be uploaded and transmitted via the system.
Do clinical investigations and performance studies that started before 21 March 2010 have to be submitted or reported retroactively to the BfArM? What changes have been made since 21 March 2010?
No. In accordance with Section 44 sub-section 4 of the Medical Devices Act (MPG), Sections 19 to 24 of the Medical Devices Act (MPG) as amended by the announcement of 7 August 2002 (German Federal Law Gazette I p. 3146), last amended by Article 1 of the Law of 14 June 2007 (German Federal Law Gazette I p. 1066) continue to apply for clinical investigations and performance studies started before 21 March 2010.
When is a clinical investigation considered to have begun?
A clinical investigation according to MDR is considered to have started ("initiated") as soon as the required approval of the higher federal authority and the consenting assessment of the ethics committee have been obtained.
A performance study according to the IVDR, on the other hand, is only considered to have begun as soon as the first subject or patient has given legally valid consent to the trial after all prerequisites for the start of the trial have been met.
Are clinical investigations / performance studies with CE-certified medical devices or in-vitro diagnostics subject to approval?
These are not clinical trials or performance studies requiring approval according to the MDR or the IVDR if the medical device is used exclusively within the scope of its intended purpose (strictly according to the instructions for use, incl. indications, contraindications, etc.) and no additional invasive or stressful examinations are carried out. In general, however, professional guidelines for the physicians involved must be observed and an appropriate ethics committee must be involved.
Are clinical investigations covered by Section 23b MPG to be notified to the BfArM?
No.
Is it possible for a sponsor based in Switzerland or Turkey to submit an application?
No. According to Article 62 (2) and (4) (c) MDR or Article 58 (4) and (5) (c) IVDR, the sponsor, if not established in the Union, must appoint a legal representative in the Union. Neither Switzerland nor Turkey is a member of the EU or a contracting state of the EEA.
How is the index to be designed to meet the relevant Essential Safety and Performance Requirements?
We recommend that a tabular list be drawn up, arranged in the rows following the Essential Safety and Performance Requirements set out in Annex I to Regulation (EU) 2017/745 (MDR) or Annex I to Regulation (EU) 2017/746 (IVDR). The list should contain further columns on the following information for each Essential Requirement: The indication whether the corresponding requirement is applicable or not, the indication of the standards or Common Technical Specifications applied in full or in part, and a description of the solutions to comply with the requirements if these standards have not been complied with or are missing. In another column of the list, we recommend indicating the relevant reference documents (e. g. documents from testing laboratories). These documents should be clearly identifiable (name, date, version number) and refer to the technical documentation. Templates for these lists can also be found on the internet.
What is meant by an evaluation and assessment of risks and benefits according to Section 3 sub-section 2 number 5 of the Ordinance on Clinical Investigations of Medical Devices (MPKPV)?
The sponsor must submit an evaluation and assessment of the foreseeable risks, disadvantages and distress for the trial subject weighed against the prospective significance of the medical device for medical science and the anticipated benefit for the trial subject.
Please note that both the risks, disadvantages and stress arising from participation in the clinical investigation / performance study as well as the risks emanating from the medical device itself are to be described.
A risk evaluation should include an estimation of the severity and the probability of occurrence.
The overall residual risk must be compared with the benefit for the trial subject as a result from his/her participation in the clinical investigation / performance study as well as with the benefit for medical science.
In the end, the sponsor must weigh the risks presented against the benefits presented in a comprehensive discussion and must conclude with a final evaluation.
Which powers of attorney should be included with the application?
In the case of an application for authorisation of a clinical investigation under the MDR or a performance study under the IVDR, a power of attorney for the legal representative of the sponsor in the Union (cf. Article 62 (2) and (4) (c) MDR or Article 58 (4) and (5) (c) IVDR) must be submitted if the sponsor itself is not established in the Union. It is recommended to submit a power of attorney signed by the sponsor and its legal representative, demonstrating that the representative is aware of its mandate and that the appropriate contractual agreements with the sponsor exist for this purpose.
If a third party (e. g. a CRO) is involved who is to take over the communication, a power of attorney must also be submitted for this party.
A clinical investigation for a medical device has already been approved by the BfArM. Is it possible to refer to the previous approval in another clinical investigation with exactly the same medical device?
In accordance with Section 3 sub-sections 2 and 4 as well as with Section 7 sub-section 2 of the Ordinance on Clinical Investigations of Medical Devices (MPKPV), the requirements for the documents to be submitted remain the same even if a new application is submitted for the same medical device.
However, it is advisable to refer to the previous clinical investigation in a cover letter which should allow a clear identification of that clinical investigation (BfArM reference number, title of the clinical investigation).
Please bear in mind that that the results of previous clinical investigations and, if applicable, of corresponding interim reports must be submitted in such cases.