DSUR Template Explained: ICH E2F Structure and Requirements

Q: What is the Reference Safety Information in a DSUR?

The RSI is the Investigator's Brochure in effect at the start of the reporting period. When an IB is not required, the relevant product label serves as RSI. The RSI version and date must be documented in Section 7.1.

Q: Does every section of the DSUR need to be completed?

Yes. ICH E2F states that all sections should be completed. When no information is available, that fact should be stated explicitly within the section. Leaving a section blank is not compliant with the guideline.

Contents

Sponsors running interventional clinical trials often carry annual safety reporting obligations under national or regional law. Where those obligations exist, ICH E2F provides the harmonized format: the Development Safety Update Report (DSUR). The guideline was finalized at Step 4 on 17 August 2010 ^[1] and is used or accepted across the US, EU, and other major ICH regions. US and EU regulators have stated that a DSUR submitted annually can take the place of the US IND Annual Report and the EU Annual Safety Report respectively, where applicable ^[1].

Get the template wrong, omit a section the guideline calls for, or miss the 60-day submission window, and regulators will notice. This guide walks through the ICH E2F DSUR structure section by section, explains the timing mechanics that govern submission, and flags the errors medical writing teams most often make.

Why the DSUR Exists and What Problem It Solved

Before ICH E2F, annual safety reporting for investigational drugs was fragmented by jurisdiction. In the United States, sponsors submitted IND Annual Reports under 21 CFR 312.33. In Europe, Annual Safety Reports were required. These documents had different formats, different scopes, and different submission rhythms. A sponsor running a multi-regional Phase II program produced overlapping documents covering much of the same safety data.

The DSUR resolved that duplication by providing a single common standard. According to the EMA's adopted text of ICH E2F (Reference Number EMA/CHMP/ICH/309348/2008, legal effective date 1 September 2011) ^[2], US and EU regulators consider a properly prepared DSUR able to take the place of the IND Annual Report and EU Annual Safety Report respectively. Health Canada adopted the E2F guidance in June 2012, with its implementation strategy for regulatory reviews effective 4 December 2015, at which point DSURs were to be provided upon request or voluntarily with a rationale ^[3].

In the United States, 21 CFR 312.33 as currently in force still requires "Annual reports," not a mandatory DSUR ^[4]. The FDA proposed a rule on 9 December 2022 ^[5] to replace that requirement with a mandatory DSUR format aligned with ICH E2F. As of June 2026, the proposed rule has not been finalized. Sponsors should monitor the regulatory docket: if the proposal is finalized, the legal obligation shifts from permissive (DSUR accepted in lieu of IND Annual Report) to mandatory, and the required content would expand beyond the current ICH E2F standard.

The ICH E2F DSUR Structure: Recommended Content and Format

ICH E2F defines the recommended content and format for the DSUR. Section 2.7.2 of the guideline ^[1] provides an explicit table of contents that implementations across ICH regions follow:

Title Page (unnumbered)
Executive Summary (unnumbered, placed before the Table of Contents)
Table of Contents

Then numbered sections 1 through 20:

Section	Title
1	Introduction
2	Worldwide Marketing Approval Status
3	Actions Taken in the Reporting Period for Safety Reasons
4	Changes to Reference Safety Information
5	Inventory of Clinical Trials Ongoing and Completed during the Reporting Period
6	Estimated Cumulative Exposure
6.1	Cumulative Subject Exposure in the Development Programme
6.2	Patient Exposure from Marketing Experience
7	Data in Line Listings and Summary Tabulations
7.1	Reference Information
7.2	Line Listings of Serious Adverse Reactions during the Reporting Period
7.3	Cumulative Summary Tabulations of Serious Adverse Events
8	Significant Findings from Clinical Trials during the Reporting Period
8.1	Completed Clinical Trials
8.2	Ongoing Clinical Trials
8.3	Long-term Follow-up
8.4	Other Therapeutic Use of Investigational Drug
8.5	New Safety Data Related to Combination Therapies
9	Safety Findings from Non-interventional Studies
10	Other Clinical Trial/Study Safety Information
11	Safety Findings from Marketing Experience
12	Non-clinical Data
13	Literature
14	Other DSURs
15	Lack of Efficacy
16	Region-Specific Information
17	Late-Breaking Information
18	Overall Safety Assessment
18.1	Evaluation of the Risks
18.2	Benefit-risk Considerations
19	Summary of Important Risks
20	Conclusions

Appendices to the DSUR

ICH E2F is explicit on completeness: "All sections should be completed; when no information is available, this should be stated" ^[1]. A section with no events in the reporting period is not left blank. It carries an explicit statement to that effect. Two practical examples: Section 11 (Safety Findings from Marketing Experience) for a drug with no approved marketing authorization would read, "No marketing authorization exists for [drug name] as of the data lock point of this report; accordingly, no post-marketing safety data are available for this section." Section 12 (Non-clinical Data) in a year with no new toxicology or in vitro studies would read, "No new non-clinical safety studies were conducted or completed during the reporting period." Both formulations document the nil finding rather than leaving an ambiguous blank. This matters during inspection, where an empty section reads as an oversight rather than a documented nil finding.

The Executive Summary: Placement and Purpose

The Executive Summary is not numbered in ICH E2F and appears before the Table of Contents, not at the end of the document. ICH E2F specifies that it should provide a concise summary of the report's important information and, together with the Title Page, can serve as a stand-alone document for submission to ethics committees and institutional review boards when required by national or regional laws ^[1]. Required content includes: the report number and reporting period, the investigational drug's mode of action and therapeutic class, estimated cumulative exposure of clinical trial subjects, marketing approval status, summary of the overall safety assessment (drawing from Section 18), summary of important risks (drawing from Section 19), any actions taken for safety reasons including IB changes, and conclusions.

Because ethics committees often circulate the Executive Summary without the full DSUR body, it must be accurate, complete, and internally consistent with the rest of the document. Any discrepancy between the Executive Summary and Sections 18 or 19 can create contradictory guidance for stakeholders who do not have access to the full report.

Timing: DIBD, Data Lock Point, and the 60-Day Window

The DSUR is annual, but it does not follow a calendar year. Its timing is anchored to the Development International Birth Date (DIBD).

The DIBD is the date of the sponsor's first authorization to conduct an interventional clinical trial in any country worldwide ^[1]. Once established, the DIBD is fixed for the entire development program. A sponsor that first received authorization in Germany in April 2019 and later initiated trials in the US and Japan continues to use April as the annual reference point for every DSUR, in every country, for as long as reporting is required.

The Data Lock Point (DLP) is the last day of the one-year reporting period measured from the DIBD. ICH E2F permits one administrative adjustment: for convenience, the DLP may be set as the last day of the month prior to the DIBD anniversary month ^[1]. Where DSUR submission is required by national or regional law, ICH E2F states that the report should be submitted to all concerned regulatory authorities within 60 calendar days of the DLP ^[1]. Those 60 days must accommodate data assembly, line listing generation, narrative writing, medical review, regulatory affairs review, quality control, and submission formatting.

Diagram

How DSUR timing works

DIBD

First authorization to conduct an interventional clinical trial anywhere worldwide

Reporting period

One-year annual safety reporting cycle anchored to the DIBD

DLP

Last day of the reporting period, with permitted administrative adjustment under ICH E2F

Submission window

DSUR submitted within 60 calendar days of the DLP where required by law

Note: The DSUR does not follow a calendar year. It follows the DIBD-based annual cycle.

Regarding duration: ICH E2F states that DSURs should continue to be submitted for as long as required by national or regional laws or regulations ^[1]. The specific stopping point varies by jurisdiction; sponsors should confirm requirements with the relevant regulatory authority in each country rather than applying a single global rule.

When both a DSUR and a Periodic Safety Update Report (PSUR) are required, ICH E2F permits the DIBD to be synchronized with the PSUR International Birth Date so that data lock points align, reducing redundant data extraction. Even when synchronized, the two documents remain separate, with different content requirements, different section structures, and different regulatory routing ^[1].

Section-by-Section Walkthrough

Sections 1-4: Administrative and Contextual Foundation

Section 1, Introduction, sets the context: the DIBD, the reporting period, the investigational drug's mechanism and indications, and the scope of clinical trials covered by the report.

Section 2, Worldwide Marketing Approval Status, provides a brief narrative of approval history: date of first approval, approved indications, approved doses, and countries with active approvals where applicable.

Section 3, Actions Taken for Safety Reasons, is often underestimated. It requires a description of significant safety-related actions taken during the reporting period by the sponsor, regulators, data monitoring committees, or ethics committees that affected either a specific trial or the broader development program. This includes partial or full trial suspensions, protocol amendments driven by safety concerns, recalls of investigational drug, risk management activities, and relevant communications to investigators. A cumulative listing of regulatory requests that limit current or future development should also be provided here ^[1].

Section 4, Changes to Reference Safety Information, records significant safety-related IB changes made during the reporting period. It is not the location for adverse event narratives; those belong in Sections 7 and 8. This section documents what changed in the reference document itself and why.

Section 5: Inventory of Clinical Trials

This section requires a brief overview of all clinical trials ongoing and completed by the sponsor during the reporting period, with detailed information presented in an appendix table ^[1]. It is one of the most frequently incomplete sections in practice, particularly for sponsors with large, multi-indication programs where trial inventory management is distributed across several operational teams. The Appendix B, Table 1 format in ICH E2F provides the recommended table structure.

Section 6: Estimated Cumulative Exposure

Section 6 covers exposure in two distinct parts. Section 6.1 addresses cumulative subject exposure in the development programme from the DIBD through the current DLP. Section 6.2 addresses patient exposure from marketing experience, for drugs that have received at least one marketing approval ^[1].

These are not interchangeable. Section 6.1 draws from clinical trial enrollment records; Section 6.2 draws from post-marketing data sources such as sales figures or patient registries. For purely investigational drugs with no marketing approval, Section 6.2 is completed with a statement that the drug has no approved marketing authorization.

ICH E2F acknowledges that exact subject counts are not always feasible and permits estimated exposure expressed in patient-years when precision is not available. The estimation method must be described and its limitations disclosed ^[2].

Section 7: Line Listings and Summary Tabulations

Every serious adverse reaction (SAR) reported to the sponsor during the interval period must appear in the line listings provided in Appendix B. The body of Section 7.1 explains which IB version was used as the reference document and the version number and date ^[1]. Section 7.2 describes case selection methodology for the interval line listings; it does not contain the listings. Section 7.3 addresses the cumulative SAE tabulation organized by System Organ Class (SOC), which must cover all sponsor-conducted clinical trials from the DIBD through the current DLP.

The cumulative tabulation must separate data for the investigational drug, active comparators, placebo, and treatment-unknown arms due to blinding ^[1]. Where blinding is maintained, the DSUR must include a cautionary statement on the title page.

Cross-functional data collection is a practical DSUR production challenge, particularly for multi-trial programs. Published DSUR authoring guidance notes that efficient teamwork across departments is essential for timely data collection, and that each functional team should begin compiling inputs before the DIBD anniversary rather than waiting for the DLP ^[8]. Different vendors may use different event coding conventions, different patient identification schemes, and different DLP cutoffs. Sponsors running multi-trial programs through multiple CROs need formal data exchange agreements and a defined reconciliation step before the medical writer can begin.

Sections 8-13: Findings Across Data Sources

Section 8, Significant Findings from Clinical Trials, is where the analytical work is most visible. The four main subsections cover completed trials (8.1), ongoing trials (8.2), long-term follow-up (8.3), and other therapeutic use of the investigational drug such as expanded access or compassionate use (8.4). Unlike the line listings, this section requires analysis and conclusions, not just description. The writer and safety physician must assess what the data mean for the evolving safety profile, not simply report that events occurred.

Section 9 covers Safety Findings from Non-interventional Studies: observational studies, registries, epidemiological analyses. Section 10 addresses other clinical trial safety information not captured elsewhere.

Section 11, Safety Findings from Marketing Experience, is relevant for drugs with a marketing approval in any jurisdiction. Post-marketing adverse event reports, spontaneous reports, and any signal activity from marketed use belong here. For purely investigational drugs, Section 11 carries a nil statement.

Section 12, Non-clinical Data, covers new toxicological or in vitro findings that emerged during the reporting period. New carcinogenicity, reproductive toxicology, or genotoxicity findings with potential implications for clinical trial subjects belong here, regardless of whether they led to an IB change. Section 13, Literature, covers relevant published literature identified during the period.

Sections 14-17: Contextual and Supplementary Information

Section 14 addresses findings from Other DSURs for the same investigational drug, relevant where multiple DSURs are being prepared, for instance across different indications developed by separate sponsors. Section 15 covers Lack of Efficacy findings that could directly affect subject safety, such as disease worsening in a serious or life-threatening indication.

Section 16, Region-Specific Information, accommodates requirements that individual regulatory authorities impose beyond the ICH E2F baseline. Certain regions require additional tables, specific safety discussions, or regulatory correspondence summaries not required globally.

Section 17, Late-Breaking Information, captures significant safety findings that emerged after the DLP but before the DSUR was submitted. Including these findings is a matter of sponsor judgment about clinical significance; ICH E2F provides no frequency threshold.

Sections 18-20: The Interpretive Core

Sections 18 through 20 carry the sponsor's interpretive judgment about the drug's benefit-risk profile. Section 18.1 evaluates the identified and potential risks: their nature, severity, frequency in the trial population, and manageability. Section 18.2 addresses benefit-risk considerations, weighing the accumulating evidence on efficacy against the safety profile observed across the development program.

Section 19, Summary of Important Risks, identifies risks that may warrant risk minimization measures, enhanced monitoring, or communications to investigators. Appendix C of ICH E2F provides example formats for this table.

Section 20, Conclusions, states the sponsor's overall position: whether the benefit-risk balance remains acceptable for continued clinical investigation, whether any aspects of the safety profile require additional study, and what actions are planned or under consideration.

These three sections are read most carefully by regulators, and in the event of a regulatory query, are the most likely to be quoted back to the sponsor. Conclusions must be specific, data-referenced, and internally consistent with the evidence presented in Sections 7, 8, and 18.

Reference Safety Information: An Important Nuance

ICH E2F specifies that the Investigator's Brochure in effect at the start of the reporting period should serve as the Reference Safety Information (RSI) for determining whether adverse events received during the year remain consistent with the known safety profile ^[1]. The RSI version number and date must be documented in Section 7.1.

There is one exception. When an IB is not required by national or regional laws or regulations, the applicable product label serves as the RSI. In the EU, that label is the Summary of Product Characteristics (SmPC); in Japan, the Japanese Package Insert; in the US, the Package Insert ^[1]. This exception applies most often to approved products whose development programs continue post-authorization. The RSI designation must be made explicitly in the DSUR and applied consistently across the reporting period.

Common Template Errors That Reach Regulatory Review

Several recurrent errors appear in submitted DSURs that regulatory reviewers may flag during review:

Incomplete section inventory

Section 5 (Inventory of Clinical Trials), Section 11 (Safety Findings from Marketing Experience), Section 12 (Non-clinical Data), and Section 13 (Literature) are frequently absent or written as one-line placeholders in first drafts. All four are sections the ICH E2F guideline calls for completing, or explicitly declaring inapplicable with a stated rationale.

Executive Summary inconsistency

The Executive Summary is prepared late in the production cycle, often after the body sections have already been revised through multiple review rounds. If the body changes and the Executive Summary is not updated in parallel, the two documents describe different safety conclusions. Because the Executive Summary may circulate independently to ethics committees, any discrepancy with Section 18 or Section 19 can create confusion for reviewers who receive both.

DLP governance failures

If different trial datasets use different effective cutoff dates, the line listings and cumulative tabulations will be internally inconsistent. A single, formally agreed DLP must govern all data extraction across all trials in the program.

Vague conclusions

Section 20 conclusions written as "the overall safety profile remains acceptable for continued development" without reference to specific findings are unlikely to satisfy reviewers. Conclusions should identify which risks are known and managed, which are being monitored, and what data are planned to resolve remaining uncertainties.

RSI version mismatch

The IB version cited in Section 7.1 must be the version in effect at the start of the reporting period, not the most current version at the time of writing. If the IB was revised during the period, both the previous and current versions are relevant, and Section 4 should describe what changed and why.

Regulatory and Documentation Considerations

The FDA Proposed Rule and What It Would Change

For sponsors holding US INDs, the December 2022 proposed rule ^[5] is material to template planning even though it has not been finalized. If adopted, the mandatory FDA DSUR would require content exceeding the current ICH E2F standard: a listing of all known important risks across the development program, an integrated safety assessment evaluating cumulative data across indications and populations, and global clinical data not limited to the specific IND ^[5]. Sponsors currently producing ICH E2F-compliant DSURs would need modest updates; sponsors still using the legacy IND Annual Report format would face a more substantial restructuring exercise.

The 60-day submission window would be retained in the proposed FDA DSUR, with the DLP defined as the calendar day before the anniversary of when the IND went into effect, or the DIBD if the sponsor prefers ^[5].

GCP, eTMF, and Source Data Traceability

DSUR source records, including line listing source data, exposure calculations, and trial status tables, should be traceable to the eTMF and primary study records. ICH E6(R3), adopted at Step 4 on 6 January 2025 ^[6], reinforces the principle that essential documents must support the reconstruction of trial conduct and verification of data integrity. A DSUR whose tabulations cannot be reconciled back to trial-level source records is a liability during inspection, regardless of whether the DSUR text itself appears complete.

How AI-Assisted Tools Fit Into DSUR Workflows

AI-assisted document tools are being applied to the structural and data-intensive elements of DSUR preparation: populating trial inventory tables from registry exports, formatting validated line listing outputs from structured safety database exports, and flagging inconsistencies between sections. ICH E6(R3) ^[6] makes clear that all records generated during clinical development must support verification and reconstruction of the trial, a standard that AI-assisted outputs must meet through human expert review before submission. Published analysis of AI in medical writing similarly notes that AI-generated text can be imprecise or fail to meet regulatory standards and requires review and correction by a skilled medical writer ^[7]. For a document that directly informs regulatory decisions about whether a development program should continue, that review is not optional.

The analytical sections, particularly Section 18 (Overall Safety Assessment) and Section 20 (Conclusions), require the judgment of a qualified safety physician and experienced medical writer. No automated tool currently replaces that judgment.

Where the productivity case is clearer is in document scaffolding and pre-population. When the structural template, including the correct ICH E2F section numbering, subsection structure, and appendix table formats, is built into the authoring environment before writing begins, medical writers spend less time on formatting and more time on content quality.

KScribe, Kitsa's AI-native regulatory document generation platform, supports DSUR authoring by maintaining the correct ICH E2F section structure and preserving cross-document consistency with the Investigator's Brochure and protocol, which matters most for the RSI version tracking in Section 7.1 and the IB change documentation in Section 4.

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DSUR authoring depends on correct ICH E2F structure, DIBD and DLP governance, RSI version tracking, line listing consistency, and safety physician review. KScribe supports AI-powered regulatory document generation across DSURs, Investigator's Brochures, protocols, and other clinical documents, helping sponsors and CROs maintain structured templates, cross-document consistency, and review-ready outputs.

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Key Takeaways

The ICH E2F DSUR template defines a Title Page and unnumbered Executive Summary before the Table of Contents, followed by 20 numbered sections (Sections 1-20) and appendices. The Executive Summary is not numbered and is not placed last.
ICH E2F states that all sections should be completed. Sections with no relevant events carry an explicit nil statement, not a blank field.
Section 5 (Inventory of Clinical Trials), Section 11 (Safety Findings from Marketing Experience), Section 12 (Non-clinical Data), and Section 13 (Literature) are sections the guideline calls for that are often missing from first-draft templates.
Section 6 is "Estimated Cumulative Exposure," with Subsection 6.1 covering cumulative subject exposure in the development programme and 6.2 covering patient exposure from marketing experience.
The DIBD anchors the annual reporting cycle. The DLP is the last day of the one-year period from the DIBD, and the DSUR should be submitted within 60 calendar days of the DLP.
The Investigator's Brochure serves as the RSI for investigational drugs; when an IB is not required by applicable law, the relevant product label takes that role.
The FDA's December 2022 proposed rule, if finalized, would make DSUR submission mandatory for all US INDs and expand required content beyond the current ICH E2F standard. As of June 2026, 21 CFR 312.33 still reads "Annual reports."

FAQ

What is a DSUR template?

A DSUR template is a pre-structured document scaffold following the recommended layout defined in ICH E2F Section 2.7.2. It includes a Title Page, an unnumbered Executive Summary, a Table of Contents, and 20 numbered content sections with subsections, followed by appendices. A properly built template includes all section headings, standard table formats for the trial inventory and line listings, and appendix placeholders, so each contributor knows exactly where their input belongs before the DLP arrives.

How is the DSUR data lock point calculated?

The DLP is the last day of the one-year period beginning on the Development International Birth Date (DIBD). The DIBD is the date of the sponsor's first authorization to conduct an interventional clinical trial anywhere in the world. For convenience, the DLP may be set as the last day of the month prior to the DIBD anniversary month. Where DSUR submission is required by national or regional law, ICH E2F states that it should be submitted within 60 calendar days of the DLP ^[1].

What is the difference between a DSUR and a PSUR?

The DSUR covers investigational drugs in clinical trials under ICH E2F; the PSUR covers post-marketing periodic safety reporting under ICH E2C(R2). When clinical development continues after marketing authorization, both may be required simultaneously. ICH E2F permits synchronization of the DIBD with the PSUR International Birth Date to align data lock points, but the two documents have different content structures and regulatory routing and must be prepared separately.

What is the Reference Safety Information in a DSUR?

For investigational drugs, the RSI is the Investigator's Brochure in effect at the start of the reporting period. When an IB is not required by applicable national or regional law, the relevant product label serves as RSI (the SmPC in the EU, the Package Insert in the US, the Japanese Package Insert in Japan). The RSI version and date must be documented in Section 7.1 of the DSUR.

How long does DSUR reporting continue?

ICH E2F states that DSURs should be submitted for as long as required by national or regional laws or regulations. The specific stopping point varies by jurisdiction. When submission is no longer required in a given country or region, the final DSUR for that jurisdiction should be identified as such, with a statement on whether clinical trials continue elsewhere.

Does every section of the DSUR need to be completed?

Yes. ICH E2F states that all sections should be completed ^[1]. When no information is available for a given section, that fact should be stated explicitly within the section. Leaving a section blank is not compliant with the guideline.