Placement of Integrated Summaries of Safety and Effectiveness (ISS/ISE) in Applications Submitted in the eCTD Format
The CTD summary sections in Module 2 are not the correct location for the integrated summaries of safety and effectiveness (ISS/ISE) required by 21 CFR 314.50 (see ICH M4: The CTD -- Efficacy Q&As.
CTD submissions are being submitted electronically, it is important that the location of ISS/ISE information in an eCTD be consistent:
- In an eCTD, the ISE and ISS go in Module 5, section 188.8.131.52.
- If the narrative portions of the ISE and ISS are suitable for use in Module 2, sections 2.7.3 and 2.7.4 of the CTD, the documents are placed once in these sections and referenced in Module 5, section 184.108.40.206 (i.e., provide leaf elements in section 220.127.116.11).
The following table lists the various sections of the CTD that contain summary and integrated discussions of efficacy and safety and the corresponding FDA regulations, where applicable, that inform the content of those sections. Any questions about these matters can be raised with the appropriate reviewing division at FDA.
|CTD Section||U.S. Regulation||Comment|
|2.5 Clinical Overview (~30 pages)|
|2.5.4 Overview of Efficacy
2.5.5 Overview of Safety
|n/a||Not a U.S. requirement, but recommended by ICH guidance|
|2.7 Clinical Summary (~50-400 pages)|
|2.7.3 Summary of Clinical Efficacy
2.7.4 Summary of Clinical Safety
|21 CFR 314.50 (c)(2)(viii)||U.S. requirement for a Clinical Summary|
|5.3 Clinical Study Reports|
|18.104.22.168 Reports of Analyses of Data from More than One Study (Including Any Formal Integrated Analyses, Meta-Analyses, and Bridging Analyses)||21 CFR 314.50 (d)(5)(v)
21 CFR 314.50 (d)(5)(vi)
|Integrated Summary of Efficacy Integrated Summary of Safety|