In the European Regulation 2017/746 (IVDR), there is no guidance on performance studies for the transition from the In Vitro Diagnostics Directive (IVDD, 98/79/EC) to the IVDR. However, the German Medical Devices Implementation Act (“Medizinprodukterecht-Durchführungsgesetz”, MPDG) contains a corresponding passage in § 100 paragraph 3:

(3) Performance evaluation studies pursuant to Section 24 of the Medical Devices Act in the version applicable up to and including 25 May 2020 that were commenced before 26 May 2022 may continue to be conducted as performance studies pursuant to Article 2(42) of Regulation (EU) 2017/746 on the basis of the provisions applicable to them up to and including 25 May 2022.

A performance evaluation study shall be deemed to have commenced within the meaning of sentence 1 if, after all requirements for the commencement of the performance evaluation study have been met, the first subject has consented to participate in the performance evaluation study.

It should be noted that performance studies subject to application under the MPDG are not considered to have started as soon as authorisation has been obtained from the competent ethics committee and the competent federal higher authority. In all cases, a performance study is only considered to have commenced within the meaning of Section 100(3) MPDG if the first subject has agreed to participate in the study by 25.05.2022 (inclusive).

Performance studies for which this condition is not fulfilled may have to be re-authorised according to the new legal framework (IVDR and MPDG).

The SAE reporting obligations must continue to be carried out in accordance with the Medical Devices Safety Plan Ordinance (“Medizinprodukte-Sicherheitsplanverordnung”, MPSV) for performance studies that are deemed to have commenced within the meaning of Section 100(3) of the MDPG, even after the IVDR becomes applicable.

The provided decision tree serves as a guide as to which performance studies are subject to approval or notification. The information from Chapter VI of the IVDR and Chapter 4 of the MPDG is decisive.

If there is a need for clarification, the BfArM decides in accordance with § 6 paragraph 3 MPDG, upon application by a competent authority or a sponsor, whether a performance study subject to approval is involved

The application for a decision on whether a performance study requires approval must be submitted independently of an application for approval according to Section 38 MPDG.

In Germany, the competent higher federal authorities are responsible for notifications of or applications for approval of performance studies with companion diagnostics (CDx). This is either the Paul Ehrlich Institute (PEI) or the Federal Institute for Drugs and Medical Devices (BfArM). To which of the two competent higher federal authorities the notification or application is to be addressed depends on the responsibility for the associated medicinal product:

According to Section 85 Paragraph 3 No. 2 MPDG, the competent higher federal authority (PEI or BfArM) is responsible for the approval of a performance study with a companion diagnostic intended for the safe and effective use of an associated medicinal product, which is also responsible for the associated medicinal product according to the Medicinal Products Act.

This question cannot be answered in a blanket manner, but depends on the individual conditions in each case. Information on this can be found on the website of the working group of ethics committees that advise on this question.

The MPDG defines the term "residual sample" as residual material of human body substances that originates from a medically indicated collection (§ 3, MPDG).

The IVDR does not define the terms. The MDR defines an invasive device as a device that enters the body, in whole or in part, through the surface of the body or through a body orifice (Article 2, 6 MDR). A surgically invasive device is an invasive device that enters the body through the body surface - including the mucous membranes of body orifices - by means of or in connection with a surgical intervention, and a device that enters the body other than through a body orifice (Annex VIII, Chapter I, 2.2, MDR).

If there is uncertainty as to whether the procedure is an additional invasive procedure or whether there are other risks to the trial subjects, the ethics committee can provide advice.
Further information from AKEK

Alternatively, a decision can be obtained from the BfArM on application to clarify the question of whether it is a performance study requiring approval.

As soon as a part of the performance study (such as recruitment, sample collection or application of the IVD) takes place in Germany, it must be checked whether the study is subject to a notification or authorisation requirement. The provided decision tree serves as an initial orientation as to which procedure is to be applied. The information from Chapter VI IVDR and Chapter 4 MPDG are decisive.

The necessary qualifications of the investigators are checked by the ethics committee when the application is submitted. Further information can be found on the AKEK website.

The IVDR refers to "devices manufactured and used exclusively within healthcare facilities established in the Union" (Article 5(5) IVDR). A "healthcare establishment" is defined in the IVDR as an organisation whose primary purpose is the care or treatment of patients or the promotion of public health (Article 2 IVDR).

The conditions to be fulfilled by health care facilities are also regulated in Article 5, paragraph 5 of the IVDR. In Germany, the respective state authorities are responsible for the supervision of health care facilities.
Overview of the competent authorities of the "Länder" in Germany

Information on SAE and DD reporting requirements can be found in the Applications and Reports section.