Development Safety Update Report (DSUR) in Review

Do you have authorization to conduct a clinical trial with your investigational drug? Do you know that you should evaluate the safety data and analyse the emerging risks during trials? During the clinical development of an investigational new medicine, it is crucial for manufacturers to periodically analyse safety information and assess the risk to trial subjects. At the same time, it is essential to inform regulators of the investigational new drug’s safety profile through a Development Safety Update Report (DSUR).

DSUR is one of the key pharmacovigilance (PV) documents for monitoring drug safety, along with the Periodic Safety Update Report (PSUR). While a PSUR is submitted for marketed drugs (post-market surveillance), a DSUR must be submitted for the drugs under development. A DSUR is a harmonized safety report that sponsors must submit to regulatory authorities such as the FDA and EMA, in accordance with ICH guidelines and the principles of ICH E2F. It should be submitted annually.

Instead of dumping the raw clinical and safety data, a DSUR must answer whether it is acceptable to expose participants to the ongoing drug development, given everything learned so far. The report shows how accurately the evolving safety profile of an investigational drug is being monitored and managed. A robust DSUR must showcase:

• clinical‑trial safety data of an investigational product
• benefit–risk thinking, and
• inspection‑readiness 

DSUR – Key Objectives

• Examine if the new data is consistent with the previous safety profile
• Describe new or emerging risks that can affect the subject protection
• A DSUR should summarise the potential risks and present a precise benefit–risk evaluation​

DSUR and ICH E2F Adherence

Across ICH regions, the DSUR has been defined as the standard format for periodic reporting, especially for drugs under development. To be compliant, it should emphasize consistency, harmonized structure, and critical analysis. As per the guideline, the data in DSUR should be organised around an annual data‑lock point. It should cover all interventional clinical trials involving the investigational product, regardless of region or sponsor type.​

Typical ICH E2F‑driven sections include:

• Introduction
• Worldwide development status, including clinical trial portfolio and exposure
• ​Actions taken for safety reasons,
• Changes in the investigational plan,
• Updates to reference safety information
• ​Cumulative subject exposure,
• New safety data (serious adverse events, signals, non‑clinical, and literature)
• Benefit–risk evaluation with conclusions 

Common DSUR audit and inspection findings

Regulatory authorities can reject a DSUR due to flaws in safety governance and sponsor oversight. The rejections may further delay clinical trials and attract penalties. The following are a few frequent issues that may lead to rejections.

• Failure to compile the DSUR as per the country-specific guidelines may lead to non-compliance.
• DSURs without rigorous quality checks, inaccurate data, and outdated safety information can compromise the report’s integrity. The data should be aligned with safety databases and clinical trial registries.
• Sponsors must follow specific timeframes for submissions. Data lock points play a key role here. If the data is not submitted within 60 calendar days from the data lock point, it may be considered non-compliant.

​In addition, there are many issues, such as weak signals and risk discussions, poor CRO oversight, fragmented ownership, and incorrect submission procedures. However, the positive factor is that many of these findings are avoidable.  With stronger planning, data discipline, and a clearer narrative mindset during DSUR drafting, sponsors can avoid discrepancies and non-compliance during audits.

Would you like to build a DSUR that withstands inspections by the FDA, EMA, or other health authorities? It’s time you stop treating it as an obligation. Consider DSUR as your annual safety blueprint for your investigational product. Start now to build one with expert benefit-risk thinking from Vigliare BP.