Submission of substantial amendments

 

The sponsor shall notify the Member State within one week whenever they intend to introduce changes to a clinical investigation that are likely to have a substantial impact on the safety, health, well-being or rights of participants or the reliability or soundness of the clinical data produced in the investigation and/or that alter the conduct of the study, the reasons for and nature of the changes.

Substantial modifications to clinical investigations follow the provisions set out in Article 75 of Regulation (EU) 2017/745, and may be implemented 38 days after notification, unless INFARMED, I.P. identifies grounds for refusal (Article 71(4)) for reasons of public health, safety or health of participants and users or public order, or a negative ethical opinion has been issued. Under the legal framework, the implementation of modifications in Portugal requires a favorable opinion from the CEIC.

In Portugal, the substantial amendment must be submitted electronically via RNEC system to INFARMED, I.P., which will coordinate with the CEIC.

The applicant must accompany the notification with:

• MDCG 2021-28 application form;
• proof of payment of the applicable fee, in accordance with Law No. 71/2025 of December 22;
• a list of the substantial amendments, the nature of these amendments and the reasons;
• all relevant documentation from the initial application dossier, which is undergoing review due to these amendments, submitted in both a clean version and a version with highlighted amendments;