Yes even more FDA guidance this week, Guidance for Industry  Intergrated Summaries of Effectivenss and Safety: Location within the Common Technical Document.

This new guidance focuses on where to place ISE and ISS documents within the structure of the CTD or eCTD. It does not outline in detail the content for the ISE and ISS. The content will be addressed in separate guidance’s.

This guidance is intended to clarify for industry where to include the integrated summary of effectiveness (ISE) and integrated summary of safety (ISS) when submitting applications in the common technical document (CTD) format. The guidance applies to applicants submitting new drug applications (NDAs) or biologic license applications (BLAs) to the Food and Drug Administration (FDA) in the CTD or the electronic common technical document (eCTD) format.

The ISE and ISS are not summaries but rather detailed integrated analyses of all relevant data from the clinical study reports that belong in Module 5. The FDA consider the ISE and ISS critical components of the clinical efficacy and safety portions of a marketing or licensing application.  However there are other modules that need this data and the FDA is providing guidance where this information should be used.

the CDT/eCDT Module 2 contains several clinical sections that are summaries, these should in general follow the outline of the ISE and ISS. It should be noted that the model 2 section is limited to 400 pates and the typical ISS alone us often substantially larger, which in itself necessitates the need for editing. The section include:

• 2.5 Clinical Overview (aropund 30 pages)
  • 2.5.4 Overview of efficacy
  • 2.5.5 Overview of safety
• 2.7 Clinical Summary (50 to 400 pages)
  • 2.7.3 Summary of Clinical Efficacy
  • 2.7.4 Summary of Clinical Safety
• 5.3 Clinical Study Reports
  • 5.3.5.3 Reports of Analyses of Data from More than One Study (including Any Formal Integrated Analysis, Meta Analysis and Bridging Analyses

Sections 2.7.3 and 2.7.4 should contain summarized information from the full ISE and ISS, only in unusual cases should the narrative parts of the full ISE or ISS and the summaries in sections 2.7.3 and 2.7.4 be the same.

Sections 5.3.5.3, should contain more detailed in-depth analysis, and unlike Module 2, Module 5 has no space limitations, Module 5 is the appropriate CTD / eCTD section for analyses containing large appendices of tables, figures and data sets typically found in an ISE and ISS.

More detail is provided in the Guidance and this should be reviewed before starting these sections in your CTD or eCTD.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.