FDA Issues Guidance on Summaries for CTD-based Submissions

The US Food and Drug Administration finalized a Guidance for Industry this week that aims to clarify the submission of new drug applications (NDAs) and biologics license applicants (BLAs) using the common technical document (CTD) format, including the electronic CTD (eCTD). Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document provides information about where in the CTD the integrated summary of effectiveness (ISE) and integrated summary of safety (ISS) should be placed. This information is required for NDAs and recommended for BLAs.

The ISE and ISS issues have created some confusion in the industry, particularly the word “summary” in both terms. According to the guidance, “A common problem with the CTD-formatted applications is that applicants incorrectly assume that the clinical summary sections satisfy the regulatory requirement for the ISE and ISS. This assumption can result in a determination by the FDA that an application is incomplete and may result in a refusal-to-file action for the application.” The document clarifies, however, “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” and not the clinical summary section.

The guidance also aims to provide specifics regarding ISS and ISE reports that are not covered in the International Conference on Harmonization (ICH) 2001 guidance M4 Common Technical Document for the Registration of Pharmaceuticals for Human Use,  specifically in M4E: The CTD-Efficacy.