In accordance with Article 75(1) of Regulation (EU) 2017/745 (MDR)

If a sponsor intends to introduce modifications to a clinical investigation that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, it shall notify, within one week, by means of the electronic system referred to in Article 73 MDR the Member State(s) in which the clinical investigation is being or is to be conducted of the reasons for and the nature of those modifications. The sponsor shall include an updated version of the relevant documentation referred to in Chapter II of Annex XV MDR as part of the notification. Changes to the relevant documentation shall be clearly identifiable.

According to Article 75(3) MDR, the sponsor may implement the modification at the earliest 38 days after the notification, unless,

a) the Member State in which the clinical investigation is being or is to be conducted has notified the sponsor of its refusal based on the grounds referred to in Article 71(4) MDR or on considerations of public health, subject and user safety or health, of public policy, or

b) an ethics committee in that Member State has issued a negative opinion in relation to the substantial modification to the clinical investigation, which, in accordance with national law, is valid for that entire Member State.

The federal higher authority must therefore inform the sponsor within 37 days of receipt of the notification if it rejects the substantial modification for one of the reasons referred to in Article 75(3) point a of Regulation (EU) 2017/745.

The time limit may be extended by a further seven days if the competent federal higher authority takes expert advice. In this case, it shall inform the sponsor no later than 20 days after receipt of the notification of the substantial modification that the time limit is extended for the purpose of consulting with experts, and at the same time point out that this also extends the time limit under Article 75(3) of Regulation (EU) 2017/745 accordingly (Section 42 of the Medical Devices Law Implementation Act, MPDG).

Other Clinical Investigation

The following applies analogously to other clinical investigations in accordance with Section 54(1) MPDG:
The sponsor shall immediately notify the competent federal higher authority and the competent ethics committee of any modifications in the (...) documents submitted via the German Medical Devices Information and Database System pursuant to Section 86 MPDG. With the notification, the sponsor shall submit an updated version of the relevant information and documentation and shall clearly identify the modifications in updated documentation.

Procedure

As long as the electronic system referred to in Article 73 (EUDAMED) is not available with a corresponding function, the German Medical Devices Information and Database System (DMIDS, formerly DIMDI) shall be used. The notification of the modification is forwarded in parallel to the competent Ethics Committee and the competent federal higher authority via the system. It must contain an updated version of the relevant documentation in accordance with Annex XV, Chapter II MDR. The modifications to the relevant documents must be clearly identified. In addition, the cover letter should address the modifications and their justification.

You can also find more information on substantial modifications in our FAQ, as well as in the MDCG Guideline on Clinical Trials (MDCG_2021-6_- Questions & Answers Regarding Clinical Investigation).