Update to FDA annual reporting requirements for INDs under White House review

By KEDEST TADESSE, MS, RAC | Jun. 14, 2022

FDA’s proposed rule to implement Development Safety Update Reports, or DSURs, for all investigational new drug applications is now under review at the White House’s Office of Management and Budget.

Regulatory Background

  • Under federal law, drug products require approval by the FDA before transportation or distribution across state lines. Therefore to test products without violating this law – the Federal Food, Drug and Cosmetic Act – companies must file and receive permission to proceed with an Investigational New Drug (IND) application, which allows them to legally test their products.
  • The IND is also used by the sponsor to demonstrate that the product is safe for use in humans. IND applications generally include data from pharmacology studies and early proof of concept studies to justify the development of the product. IND submissions also generally contain animal pharmacology and toxicology studies, clinical protocol and investigator information for the proposed human clinical study, and manufacturing information on the investigational product. An IND is neither approved nor rejected; rather, the FDA takes 30 days to review the original submission and will either allow for the clinical study to proceed or will issue a clinical hold.
  • Under 21 CFR 312.22, sponsors are required to submit an Annual Report to the FDA within 60 days of the anniversary date on which the IND was “clear to proceed.” Annual reports are required to contain a summary of the status of every clinical and nonclinical study in progress or completed within that year, as well as any relevant information such as adverse events and safety reports, an updated general investigational plan, an updated investigator brochure, manufacturing changes and protocol amendments not previously submitted and foreign marketing status.

In 2010, the Development Safety Update Report was proposed to “replace existing annual reporting requirements in the US and EU.”

  • To ensure comprehensive safety analyses and increase harmonization, the International Council on Harmonization (ICH) proposed a guideline, E2F Development Safety Update Report (DSUR). According to the document, the DSUR “is intended to be a common standard for periodic reporting on drugs under development (including marketing drugs that are under further study) among the ICH regions.” The DSUR would meet the requirements of both FDA’s IND Annual Report requirements and the EU’s Annual Safety Report.
  • The FDA adopted the guideline in 2011 and the DSUR applies to all drugs, biologics and vaccines. According to the guideline, the DSUR will allow sponsors to “present a comprehensive, thoughtful annual review and evaluation of pertinent safety information collected during the reporting period related to a drug under investigation, whether or not it is marketed.”
  • In contrast to an annual report, for which a company can submit the required data in its own format, the DSUR has a distinct format. A DSUR contains an introduction to the product, a note on worldwide marketing approval status, any action taken during the reporting period for safety reasons, other safety information, a listing of ongoing and completed clinical studies, an estimate of cumulative exposure, significant trial findings, safety data from non-interventional studies, a summary of important risks and other relevant information in an organized manner.

Now the FDA has completed preliminary work on a proposed regulation that is undergoing review at the White House that would switch all US IND Annual Reports submissions to use a DSUR.

  • Today the White House Office of Information and Regulatory Affairs posted that it has received a proposed rule from the FDA for review. The official summary of the rule reads that it would, if finalized, “amend FDA’s requirements concerning annual reports submitted by sponsors to investigational new drug applications (INDs) by replacing FDA’s current annual reporting requirement with a new requirement for an FDA development safety update report (FDA DSUR).” The announcement notes the DSUR will be “more comprehensive” and “informative” than the IND annual report currently in use.
  • Impact. Many sponsors, especially those with products in the EU, have already switched to DSURs in the last decade. Thus, the effect on bigger companies might be minimal. However, a DSUR preparation is a significant undertaking due to its content and format requirement compared to a US IND annual report. As such, sponsors may need to start preparation of a DSUR earlier than a regular annual report since it requires more data and analysis.
  • OIRA’s reviews of regulations typically last between several weeks and several months, depending on a variety of factors including the complexity of the change, the status of other rulemaking at OIRA (i.e., volume of other requests) and the overall economic costs of the rulemaking.

To contact the author of this analysis, please contact Kedest Tadesse.
To contact the editor of this piece, please contact Alec Gaffney

Key Dates and Documents