Periodic Benefit-Risk Evaluation Report (PBRER)
ICH E2C(R2) defines the format, content, and timing of the Periodic Benefit-Risk Evaluation Report (PBRER), the post-authorisation report that superseded the earlier Periodic Safety Update Report concept. It shifts periodic reporting from an interval listing of adverse events toward an integrated evaluation of a medicine's benefits and risks, drawing on both the cumulative and the interval experience. The guideline sets a defined section structure and a reporting cadence anchored to the International Birth Date and Data Lock Point. In the EU the PBRER serves as the PSUR under good-pharmacovigilance-practice Module VII; in the US it maps to the periodic reporting framework.
What this does not cover
stated in the document's own scope- It does not govern expedited individual case reporting during development; ICH E2A defines those definitions and timelines.
- It does not specify the electronic transmission format for individual case safety reports, which is ICH E2B.
- It is a post-authorisation report and does not replace the development safety update report used during clinical trials.
- It does not set the risk-management-plan structure, which is handled separately in regional pharmacovigilance guidance.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
ICH E2C(R2) reshaped periodic post-marketing reporting. Its predecessor, the Periodic Safety Update Report, was essentially an interval catalogue of adverse events. The PBRER keeps that safety information but places it inside a broader question: does the medicine's benefit still outweigh its risk across its authorised uses? The report integrates cumulative and interval data, summarises exposure, evaluates new signals against what was already known, and reaches an explicit benefit-risk conclusion. Its timing is governed by the International Birth Date and a Data Lock Point, so one core report can serve multiple regions with regional differences handled through addenda.
Legal basis & how it acquires force
E2C(R2) is a harmonised guideline that acquires legal force through regional implementation. In the EU the PBRER is the legal PSUR required by the pharmacovigilance legislation and detailed in good-pharmacovigilance-practice Module VII; the EMA adopted the guideline as a CHMP scientific guideline. In the US it is recognised within the periodic safety reporting framework under FDA regulations. Marketing-authorisation holders submit the report to the schedule set by each regulator, referenced to the medicine's International Birth Date.
Document structure
| Part | Covers |
|---|---|
| Introduction and worldwide status | Product background, reporting period, and marketing-authorisation status across markets |
| Actions and reference information | Actions taken for safety reasons and changes to the reference safety information during the period |
| Exposure | Estimated cumulative and interval patient exposure from trials and marketing use |
| Data in summary tabulations | Cumulative and interval adverse-event data and signal information |
| Signal and risk evaluation | Evaluation of signals and of important identified and potential risks and missing information |
| Benefit-risk evaluation and conclusions | Integrated benefit-risk assessment for authorised indications and the overall conclusions |
Key requirements
- Compile the report to the defined PBRER section structure, integrating benefit and risk rather than listing safety data alone.
- Anchor the reporting period to the International Birth Date and Data Lock Point, and submit to the required cadence.
- Evaluate new information against the cumulative experience, not only the interval since the last report.
- Summarise the estimated exposure and the populations exposed as the denominator for the benefit-risk assessment.
- Present an integrated benefit-risk analysis for the authorised indications, including the effect of new safety information.
- Describe actions taken for safety reasons and changes to the reference safety information during the period.
- Draw conclusions on whether the benefit-risk balance remains favourable and identify any needed changes.
Implementation tips
- Maintain a single reference safety information document so interval changes feed the PBRER consistently.
- Track exposure estimates continuously rather than reconstructing them at the data lock point.
- Align the report period with the International Birth Date early, especially where regional cycles differ.
- Build the benefit section from the outset — treating the report as safety-only is the most common structural gap.
Where this control fails
live FDA enforcementLive FDA recalls SPEQ maps to this standard’s topics — a SPEQ interpretation, not an FDA classification.
International alignment
E2C(R2) applies across the EU, Japan, and the United States. In Europe it is the format of the legally required PSUR and is assessed through the single-assessment procedure; in the US it fits the periodic reporting framework. It builds on ICH E2A, which defines the safety terms and expedited-reporting concepts used throughout, and connects to ICH E2B, the electronic format for individual case safety reports that feed the summary tabulations.
ICH E2C(R2): frequently asked questions
Quick answers to common questions about ICH E2C(R2).
What replaced the PSUR?
The PBRER defined in ICH E2C(R2) superseded the earlier PSUR concept, shifting from an interval safety listing to an integrated benefit-risk evaluation. In the EU the PBRER is the legal PSUR.
What are the International Birth Date and Data Lock Point?
The International Birth Date is the date of the first marketing authorisation for the product anywhere; the Data Lock Point is the cut-off date for the data in a given report. Together they set the reporting cadence.
How does the PBRER differ from a PSUR in content?
It retains the safety data of a PSUR but adds estimated exposure, cumulative context, and an explicit integrated benefit-risk evaluation and conclusion for the authorised indications.
When was E2C(R2) finalised?
It reached ICH Step 4 on 17 December 2012.
This standard in practice
Recall domain is a SPEQ mapping of this standard’s topics, not an FDA classification.