How to Submit a Substantial Amendment Notification

 

After the beginning of a clinical trial, the sponsor may introduce changes to the protocol or make other amendments. If these have an impact on the safety and rights of participants and/or alter the reliability and robustness of the data generated in the clinical trial, they are classified as substantial modifications and therefore require authorisation from INFARMED, I.P. and/or a favourable opinion from CEIC.

All applications for substantial modification of clinical trials must be submitted through the Clinical Trials Information System (CTIS).

The timeframe for the assessment of a Substantial Modification under Regulation (EU) No 536/2014 is, as a rule, 38 days following validation, and may be extended if requests for clarification are made.

The process follows a structure similar to that of the initial application, but with shorter timeframes:

 

Phases of the Procedure

  • Validation (6 days): Member States verify whether the application is complete.
  • Assessment (38 days): Analysis of the regulatory and scientific aspects (Part I) and/or national/ethical aspects (Part II).
  • Decision (5 days): Timeframe for notification of the final decision following completion of the assessment.

If the authorities request additional information, the timeline is suspended and the total timeframe may be extended by up to 31 days:

  • Sponsor's Response: Up to 12 days to provide the clarifications.
  • Assessment of the Response: Up to 19 days for the authorities to analyse the new data.

 

Important Notes:

  • Tacit Approval: As with the initial trial application, if the Member States do not respond within the regulatory timeframes, the modification is deemed to be authorised.
  • Non-Substantial Modifications: These do not require prior authorisation and need only be submitted in CTIS.

 

Applicable Regulatory Provisions:

Regulatory provisions applicable to the submission of applications to conduct a Clinical Trial as well as applications for Substantial Modification, Notification of Clinical Trial Completion and Final Report and other Notifications: