5 Reasons to Get Excited About the FDA DSUR Format

Are you working on annual submissions that utilize the current FDA Annual Report format? Are you concerned about the mandatory adoption of the FDA DSUR (development safety update report)?

Below are five reasons to embrace the change and place the DSUR at the center of a productive cross functional submission strategy emphasizing continuity and consistency of risk management.

Harmonization

The DSUR streamlines annual report preparation by enabling simultaneous submission in all regions based on a single date.

Under the new § 21CFR 312.33 annual reporting requirement, the content and format of the proposed FDA DSUR aligns with the E2F DSUR supported by International Council for Harmonization (ICH) and safety reporting requirements in other countries.

Submitting the DSUR format to all ICH regions creates a more uniform and efficient annual reporting process, enabling regulatory authorities in multiple world regions to access the same data within the same timeframe.

Synchronicity

The DSUR synchronizes annual updates with updates to the reference safety information (RSI), which is captured in the investigator’s brochure (IB) during development. The RSI is a list of adverse reactions (ARs) that is used to determine the expectedness of Suspected Unexpected Serious Adverse Reactions (SUSARS) for safety reporting purposes.

When drafting a DSUR, the RSI in effect at the beginning of the reporting period serves as the RSI during the reporting period, effectively setting a baseline for assessing any new ARs while providing context for the updated IB. The ultimate effect of this synchronization will be increased compliance across regions and consistency in SUSAR reporting.

Content

The DSUR is ICH harmonized in structure and content, thereby providing a single platform for risk identification, tracking, and mitigation. Compared to the FDA annual report format, the DSUR is a more substantive, comprehensive, and informative report that requires additional safety information earlier in the reporting process, such as a summary of cumulative pertinent safety information and an integrated overall safety analysis.

Sponsors are, therefore, better positioned to identify safety signals early in the course of development and to provide consistent updates as risk profiles evolve.

The FDA DSUR requirements will also ensure greater predictability and consistency in regulatory reviews and actions across different countries and regions, as the regulatory authorities will be provided with a consistent description of a drug product’s safety profile.

Connection

The DSUR is a cross-functional document summarizing information from non‑clinical, clinical, and pharmacovigilance experts in an exercise specifically focused on identifying risks and their mitigation. Thus, the format is aligned with the FDA’s focus on benefit-risk in the assessment of new drugs.

Completing the DSUR allows Sponsors to effectively check the vital signs of a program and ensure potential benefits continue to outweigh the risks throughout development and up to the time of the marketing application.

Continuity

Over the course of development, DSUR provides a continual narrative of a program, consolidated across disciplines, specifically focused on the most critical aspects of risk management. Therefore, a well-structured DSUR provides some insurance in the event of turnover within development teams and can also be attractive in potential acquisitions.

From increased‑efficiency of safety reporting to ease of harmonization and overall risk management, Sponsors who embrace the DSUR will find that the benefits of the format accrue quickly.

Let MMS guide you through the DSUR transition. Our experts will position your team to get the most out of the format from a reporting perspective and ensure that the creation of the document is part of a seamless, integrated risk management process. Get in touch with our experts here.

Authors:
Ben Kaspar, Director, Regulatory Affairs and
Christine Clarke PhD, Senior Manager, Regulatory Affairs

Reference:

Federal Register : Investigational New Drug Application Annual Reporting

ICH guideline E2F on development safety update report