Performance Studies

Whether an IVD performance study must be authorised by the competent federal authority and when the performance study may begin depends on whether the IVD already bears a CE marking or not. The legal basis can be found in Regulation (EU) 2017/746 ("IVD Regulation", IVDR) and the Medical Devices Implementation Act (Medizinprodukterecht-Durchführungsgesetz, MPDG).

Performance Study with an IVD without CE marking

A performance study with an IVD that does not yet bear a CE marking must be authorised by the competent higher federal authority if:

• a. surgically invasive sample-taking¹ is done only for the purpose of the performance study (Article 58 (1) (a) IVDR) or
• b. it is an interventional clinical performance study² (Article 58 (1) (b) IVDR) or

• c. the conduct of the study involves additional invasive procedures or other risks for the subjects of the studies (Article 58 (1) (c) IVDR).
  
  

  ¹ The IVDR does not define the concept of surgically invasive sample-taking. Following the definition of a surgically invasive device in Chapter I, 2.2 of Annex VIII to Regulation (EU) 2017/745, it is implied that a surgically invasive procedure is a surgical procedure or related to the penetration of a device into the body through the body surface, either through mucous membranes of body orifices or through a means other than a body orifice. According to Regulation (EU) 2017/745 ('Medical Device Regulation' (MDR)), Annex VIII, Chapter I, 2.2, a surgically invasive device is 'an invasive device which penetrates inside the body through the surface of the body, including through mucous membranes of body orifices with the aid or in the context of a surgical operation, and a device which produces penetration other than through a body orifice'.
  
  

  ² 'Interventional clinical performance study' means a clinical performance study where the test results may influence patient management decisions and/or may be used to guide treatment (Article 2 (46) IVDR).

If none of these points apply to your performance study, there is no obligation receive authorisation from or notify the competent higher federal authority.

If one of these points (a, b, or c) applies to the performance study, authorisation of the performance study is required. The type of authorisation procedure and when the performance study may begin will depend on which of the following points apply.

Type of Performance Study	Type of Authorisation Procedure and Start of the Performance Study
a. (Variant 1) Performance study in which surgically invasive sample-taking is done solely for the purpose of the performance study and in which sampling does not pose a significant clinical risk to subjects.	The performance study may commence if the competent higher federal authority has not objected within ten days of the validation date and the competent ethics committee has given an affirmative opinion (section 31a (1) MPDG).
a. (Variant 2) Performance study in which surgically invasive sample-taking is done solely for the purpose of the performance study and in which the sampling does pose a significant clinical risk to the subjects.	The performance study may commence if the competent higher federal authority has granted an authorisation of the performance study and the competent ethics committee has given an affirmative opinion. The competent higher federal authority is given 10 days for the application validation and a subsequent period of 45 days for the authorisation (Article 66 paragraph 7b IVDR).
b. Performance study that is an interventional clinical performance study.	The performance study may commence if the competent higher federal authority has granted an authorisation of the performance study and the competent ethics committee has given an affirmative opinion. The competent higher federal authority is given 10 days for the application validation and a subsequent period of 45 days for the authorisation (Article 66 paragraph 7b IVDR).
c. Performance study that involves additional invasive procedures or other risks for the subjects of the studies.	The performance study may commence if the competent higher federal authority has granted an authorisation of the performance study and the competent ethics committee has given an affirmative opinion. For the competent higher federal authority, there is in principle a period of 10 days for the application validation and a subsequent period of 45 days for the approval (Article 66 paragraph 7b IVDR).

Performance study with an IVD with CE marking (pursuant to Article 18 (1) IVDR)

In the case of a performance study with an IVD that already bears the CE marking referred to in Article 18 (1) IVDR, the sponsor shall, in accordance with Article 70 (1) IVDR, inform the Member States concerned at least 30 days before the start of the performance study if any of the following points are applicable:

• The performance study serves to further evaluate the product within the scope of its intended purpose and
• in the performance study, subjects are submitted to additional procedures that are invasive or burdensome compared to those performed under normal conditions of use of the device.

In Germany, this notification must be made to the higher federal authority responsible for the IVD.

In the case of a performance study with an IVD already bearing the CE marking referred to in Article 18 (1) IVDR in which:

• the IVD is used in the performance study within its intended purpose, and
• subjects shall not be subjected to additional invasive or burdensome procedures compared to normal use,

there is no obligation receive authorisation from or notify the competent higher federal authority.

For a performance study with an IVD that already bears the CE marking in accordance with Article 18 (1) IVDR but is used in a manner other than its intended purpose in the performance study, Articles 58 to 77 IVDR shall apply, and therefore the same rules shall apply as for an IVD without CE marking.

Performance Studies with Companion Diagnostics

If the IVD to be used in the performance study is a companion diagnostic, the same requirements apply as for performance studies of IVD without CE marking described in Article 58 (1) IVDR (Article 58 (2), Sentence 1, IVDR).

Exception: If only left-over samples are used in a performance study involving companion diagnostics, the performance study is not subject to authorisation. However, such a performance study must be reported to the competent higher federal authority in accordance with Article 58 (2) sentences 2 and 3 IVDR and Section 31b MPDG. The necessary appendices and documents for notifications of these performance studies are described in Section 31b paragraph 2 MPDG.

Procedure for Submitting an Application

Pursuant to Section 38 (1) MPDG, the sponsor shall submit the application for authorisation of a performance study for which authorisation is required to the competent higher federal authority in German or English. The application shall contain the information and documents referred to in Chapter II of Annex XV to Regulation (EU) 2017/745 or Chapter I of Annex XIV to Regulation (EU) 2017/746 and the opinion of the competent ethics committee.

In order to initiate the authorisation procedure for performance studies of in vitro diagnostic medical devices (IVD), an application must be submitted to the Paul-Ehrlich-Institut via the German Medical Device Information and Database System (Deutsche Medizinprodukteinformations- und Datenbanksystem, DMIDS). The application shall be submitted via the electronic system in accordance with Article 66 of the IVDR. This generates a unique, EU-wide identification number for the performance study, which is used for all communication in connection with this performance study (Article 66 (1) IVDR).

The applicant will receive a confirmation of receipt of the application via the DMIDS medical device portal and will continue to receive information about the status of the proceedings (e.g. regarding documents to be submitted or about the approval of the application).

Decision Tree of the Federal Institute for Drugs and Medical Devices (BfArM)

The Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) provides a decision tree for performance studies IVDR/MPDG on its website as an aid for the classification of your performance study.

Serious Adverse Events (SAEs)

The sponsor of the performance study must immediately report the following events in accordance with Article 76 (2) of the IVDR:

• a) any serious adverse event that has a causal relationship with the device, comparator, or study procedure or where a causal relationship is reasonably possible;
• b) any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;
• c) any new findings in relation to any event referred to in Article 76 (2) (a) and (b) of the IVDR.

The sponsor must ensure that the registration form for SAEs published by the Paul-Ehrlich-Institut is used.

Contacts at the Paul-Ehrlich-Institut

Prior to submitting the application, the sponsor may contact the Paul-Ehrlich-Institut regarding performance studies with IVDs via biovigilance@pei.de and regarding performance studies with companion diagnostics via cdx@pei.de.

Further Information

DMIDS - German Medical Device Information and Database System
Performance Study Decision Tree
SAE Notification Form (German only)

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