What is the FDA’s New Annual Reporting Requirement for INDs?

The FDA recently proposed to replace its current annual reporting requirements for Investigational New Drug (IND) applications with Development Safety Update Reports (DSURs).

What Does the FDA’s Proposed Change Mean?

Under 21 CFR 312.33, FDA requires Sponsors with an IND in effect to submit an IND annual report.

In 2011, the FDA adopted the International Council on Harmonization (ICH)’s guidance, the E2F DSUR, and began accepting the DSUR in place of the IND annual report.  

Now, the FDA is proposing switching all US IND Annual Reports to the use of a DSUR instead.

The proposed change means that Sponsors with an IND in effect will be required to submit an annual FDA DSUR instead of the IND Annual Report.

What Are the Differences Between the FDA DSUR Requirements and the IND Annual Report?

The FDA anticipates that the proposed annual FDA DSUR will retain the general aspects of the current IND annual report but will include more comprehensive information.

For example, the new FDA DSUR will include a requirement for an integrated overall safety analysis and a summary of cumulative pertinent safety information.

Other proposed additions include requiring Sponsors to provide the following:

• A cumulative summary tabulation of serious adverse events obtained from all clinical investigations conducted on behalf of the Sponsor that occurred since the date the IND went into effect
• A cumulative listing and a brief description of all important known risks and potential risks associated with the use of the drug identified by the Sponsor throughout the drug’s studies conducted on behalf of the Sponsor

The requirements are expected to be similar in format and content to those currently detailed in the E2F DSUR guidelines.

Benefits of the Proposed FDA DSUR Requirement

As clinical trials continue to increase in complexity, the FDA’s decision to require a DSUR will make it easier for FDA and Sponsors to capture and characterize the evolving safety profile of an investigational drug as a DSUR offers a more comprehensive and informative assessment of risk than the IND Annual Report.

Stakeholders would be able to identify and manage new safety findings impacting the protection of study subjects and reduce patients’ exposure to unnecessary risks.

Because FDA intends for its DSUR to be consistent with the format and content of the ICH’s DSUR, the annual reporting process for Sponsors would be more efficient, as they only need to support one format to submit to multiple regulatory authorities across different countries and regions.

This proposed change is consistent with FDA’s overarching goal of fostering the international harmonization of regulatory requirements to the extent that they are appropriate and feasible.

What Are Some Potential Challenges with the Proposed Change?

FDA acknowledges that switching to a DSUR will likely require more resources to develop as it is more robust than previously required. However, FDA expects that this will be offset by mitigating the previous regulatory burden on Sponsors who had to submit multiple reports to regulatory authorities across countries or regions.

In addition, should ICH update its DSUR guidelines, FDA may evaluate the proposed regulation to determine if any corresponding updates are necessary.

What Does This Mean for Sponsors?

The proposed changes will affect Sponsors differently based on the type of IND Annual Report they currently submit.

Sponsors who submit IND Annual Reports that follow the current 21 CFR 312.33 requirements will bear the biggest impact of the proposed change, as they will have to transition to the FDA DSUR. These Sponsors may consider transitioning to the DSUR in their next cycle.

Few changes are anticipated for Sponsors who submit the E2F DSUR in lieu of the IND Annual Report.

If you need support completing IND Annual Reports or any type of periodic aggregate reports ((including but not limited to PBRERs, PADERs, or DSURs), email info@mmsholdings.com to be connected to an expert.

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Authors: MMS Safety Writing Team