The DSUR explained: what Phase 1 and Phase 2 sponsors need to know

A Series B oncology company in year two of a Phase 2 trial receives a question from their EU clinical trial site coordinator: has the DSUR been submitted? The CMO — who has been focused entirely on efficacy data — has never heard of a DSUR. Thirty seconds of searching reveals that the first annual DSUR was due eight months ago. This situation is more common than it should be.

What is a DSUR?

The Development Safety Update Report is an annual safety report for investigational medicinal products (IMPs) in clinical development. It is mandated by ICH E2F (published 2011) and required under EU CTR 536/2014 for all clinical trials conducted in the EU/EEA. The FDA equivalent for IND holders is the IND Annual Report under 21 CFR 312.33, which has some overlapping content but different structural requirements.

The DSUR covers a 12-month period anchored to the Development International Birth Date (DIBD) — the date of the first regulatory approval of the IND or clinical trial application, in any country, for any indication. If your IND was approved on March 15, 2024, your first DSUR covers March 15, 2024 to March 14, 2025 and is due within 60 days of the data lock — typically by approximately May 14, 2025.

What goes in the DSUR

ICH E2F specifies the content in 19 sections. The key sections that require the most preparation are:

• Clinical overview of the development programme — all ongoing and completed studies, total exposure
• SUSAR line listing — all SUSARs from all studies during the reporting period
• Significant safety findings from clinical trials — deaths, discontinuations for adverse events, laboratory findings
• Safety findings from non-clinical studies — any new animal data with safety implications
• Literature review — published data on the drug class relevant to safety
• Safety conclusions and benefit-risk assessment — your summary view of the evidence

Submission requirements

Under EU CTR 536/2014, DSURs for EU trials must be submitted via CTIS to all relevant Member States. The submission timeline is within 60 days of the end of the reporting period. For IND studies in the US, the IND Annual Report must be submitted within 60 days of the IND anniversary date. If you have trials in multiple jurisdictions, you may be submitting multiple annual reports at different times.

Many small sponsors use the DSUR as their single annual safety report and submit it to all regulators, with jurisdiction-specific appendices where needed. This is acceptable under ICH E2F principles and reduces duplication.

Common mistakes

The most common DSUR failures at small companies are: not knowing the DIBD (and therefore missing the first submission deadline entirely), incomplete SUSAR line listings due to poor case tracking during the year, and a benefit-risk section that consists of one sentence. The benefit-risk assessment in a DSUR must be a genuine analysis, not a boilerplate statement.

Nimble PV prepares DSURs for Phase 1-3 sponsors with one or multiple investigational products. Talk to Vera at nimblepv.com.