Daily Rules, Proposed Rules, and Notices of the Federal Government
FDA is announcing the availability of a guidance for industry entitled “Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document.” This guidance is intended for applicants submitting an NDA or BLA in the CTD or electronic common technical document (eCTD) format. Since FDA adopted the CTD, a standard way to organize a marketing or licensing application, there has been confusion regarding where to place an ISE and ISS within the CTD. The ISE and ISS are unique requirements of the United States and are not addressed fully by ICH M4E.
FDA considers the ISE and ISS critical components of the clinical efficacy and safety portions of a marketing or licensing application. Therefore, the ISE and ISS are required in NDA applications submitted to FDA in accordance with the regulations in 21 CFR 314.50(d)(5)(v) and (d)(5)(vi)(a). Although there are no corresponding regulations requiring an ISE or ISS for BLAs, applicants are encouraged to provide these analyses.
A common problem with the way many of the CTD-formatted applications are submitted is that applicants incorrectly assume that the clinical summaries in Module 2 satisfy the regulatory requirements for the ISE and ISS. This assumption can result in a determination by FDA that an application is incomplete. Despite their names, the ISE and ISS are detailed integrated analyses of all relevant data from the clinical study reports, not summaries. This guidance focuses on where to place ISE and ISS documents within the structure of the CTD or eCTD.
This guidance updates the part of sections II.G. and H. of the guidance on the “Format and Content of the Clinical and Statistical Sections of an Application” that relates to placement of the ISE and ISS. This guidance finalizes the draft guidance of the same title that published in the
This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the agency's current thinking on the location for an ISE and ISS within the CTD. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.
Interested persons may submit to the Division of Dockets Management (see
Persons with access to the Internet may obtain the document at