PSUR and PBRER Format: ICH E2C(R2) Section by Section

PSUR and PBRER refer to the same document. The Periodic Safety Update Report (PSUR) is the older, more widely used name; the Periodic Benefit-Risk Evaluation Report (PBRER) is the name ICH gave the report when it revised the format in guideline E2C(R2). Regulators and industry use the terms interchangeably in practice — the EU’s own pharmacovigilance legislation still says “PSUR” while pointing to the E2C(R2) format for its content. This guide covers the E2C(R2) structure section by section, the data lock point and reporting-interval rules that govern when a PSUR/PBRER is due, the integrated benefit-risk evaluation at its center, and the EU’s single assessment procedure for products that share an active substance across multiple marketing authorisations.

This guide covers the pharmacovigilance PSUR — the periodic aggregate safety report a marketing authorisation holder (MAH) files for an authorised medicinal product. It is a different document from the medical device PSUR required under EU MDR Article 86, which follows MDCG guidance rather than ICH E2C(R2) and is scoped to a device rather than a drug substance.

Why the report has two names

ICH first standardised periodic aggregate safety reporting in guideline E2C, adopted in 1996. In 2012, ICH replaced it with E2C(R2): Periodic Benefit-Risk Evaluation Report (PBRER), which kept the same reporting-interval logic but restructured the report around an explicit benefit-risk evaluation rather than a safety-only summary. The EU adopted the E2C(R2)/PBRER format into its own pharmacovigilance legislation (Good Pharmacovigilance Practices Module VII) while retaining the legacy term “PSUR” in the regulation text itself, so in EU submissions a document titled “PSUR” is, in substance, built to the PBRER structure. The FDA and other ICH-region regulators follow the same convention. A drafter preparing one of these reports needs to know both names refer to one format — there is no separate “PSUR-only” template distinct from PBRER within ICH-harmonised jurisdictions.

PBRER structure section by section (ICH E2C(R2))

E2C(R2) specifies a standard section order so that the same report can be submitted, largely unchanged, across ICH regions. A complete PBRER includes:

1. Title page — product name, active substance(s), MAH, reporting interval covered, and data lock point date.
2. Executive summary — a concise synopsis of the report’s benefit-risk conclusion, written for a reader who will not read the full document.
3. Introduction — product background, therapeutic indication(s), and the reporting interval this submission covers.
4. Worldwide marketing authorisation status — every jurisdiction where the product is authorised, with authorisation dates and any conditions.
5. Actions taken for safety reasons during the reporting interval — label changes, restrictions, suspensions, or withdrawals prompted by safety findings.
6. Changes to reference safety information — what changed in the Company Core Safety Information / reference safety information used to assess reports as expected or unexpected.
7. Estimated exposure and use patterns — patient exposure data (cumulative and interval), by indication, dose, route, and region where available.
8. Data in summary tabulations — tabulated serious adverse reactions from spontaneous reports and study data for the interval.
9. Summary of significant findings from clinical trials during the reporting interval — completed and ongoing trials, including negative or inconclusive results relevant to safety.
10. Findings from non-interventional studies — observational and registry data bearing on safety or effectiveness.
11. Information from other clinical trials and sources — investigator-sponsored trials, compassionate-use programs, and other non-MAH-sponsored data.
12. Non-clinical data — new toxicology or pharmacology findings from the interval.
13. Literature — published case reports and studies bearing on the product’s safety.
14. Other periodic reports — cross-reference to any other aggregate report (e.g., a Development Safety Update Report still running for an unapproved indication).
15. Lack of efficacy in controlled clinical trials — relevant for products where reduced efficacy carries a safety implication.
16. Late-breaking information — material safety information that emerged after the data lock point but before submission.
17. Overview of signals: new, ongoing, or closed — the signal-management summary feeding the evaluation sections that follow.
18. Signal and risk evaluation — the detailed assessment of each signal and identified/potential risk.
19. Benefit evaluation — a summary of the evidence for efficacy/effectiveness, refreshed each interval rather than re-litigated from scratch.
20. Integrated benefit-risk analysis — the section covered in detail below.
21. Conclusions and actions — what, if anything, the MAH proposes to change (labeling, risk-minimisation measures, further studies).
22. Appendices — supporting tabulations, reference information, and the actual reference safety information document.

Not every section applies to every product in every interval — E2C(R2) explicitly allows a section to be stated as “not applicable” with a brief reason rather than padded out, which keeps the report proportionate for well-established, low-signal products.

Data lock point and reporting-interval rules

The data lock point (DLP) is the cutoff date for data included in a given PSUR/PBRER: every adverse-event report, study result, and literature finding received up to that date goes in; anything received after goes into the next interval’s report (or, if safety-significant, into the “late-breaking information” section as an interim flag). The DLP anchors the whole report — exposure estimates, tabulations, and the benefit-risk evaluation are all as-of that date, which is why the title page states it explicitly.

Reporting intervals are set relative to the International Birth Date (IBD) — the date of the first marketing authorisation for the product anywhere in the world. The general default under ICH E2C(R2) and EU GVP Module VII is:

• Every 6 months for the first 2 years after the IBD.
• Annually for the following 2 years.
• Every 3 years thereafter, unless a shorter interval is imposed.

In the EU this default is overridden product-by-product through the EURD list (European Union Reference Dates and frequency of submission of PSURs) — a legally binding list maintained by the EMA that sets the actual data lock points and submission dates for each active substance, and can require more or less frequent reporting than the ICH default based on the product’s risk profile, how long it has been on the market, or specific PRAC/CHMP decisions. A MAH does not calculate its own PSUR schedule from the IBD by default in the EU; it checks the EURD list for the active substance in question, and follows that instead.

The integrated benefit-risk evaluation

The section that most distinguishes PBRER from the older, safety-only PSUR format is the integrated benefit-risk analysis. Rather than presenting safety data in isolation, E2C(R2) requires the MAH to weigh newly identified or characterised risks from the reporting interval against the evidence for benefit summarised earlier in the same report, for each approved indication (or population, where benefit-risk differs meaningfully by population). The evaluation is expected to:

• State the benefit-risk conclusion explicitly for each indication, not just describe the underlying data and leave the conclusion implicit.
• Explain how newly characterised risks change (or don’t change) the benefit-risk balance compared with the prior report.
• Reference the product’s risk management plan (RMP) where one exists, since risk-minimisation measures already in place are part of what makes a given risk acceptable.
• Distinguish identified risks, potential risks, and important missing information — the same risk categories used in the RMP — so the benefit-risk narrative and the risk-management documentation stay consistent with each other.

This is also the section regulators scrutinise most closely during assessment, since it is where the MAH is making an affirmative claim rather than just reporting data.

The EU single assessment procedure (PSUSA)

Where a substance is authorised under more than one marketing authorisation in the EU — originator and generics, or multiple MAHs holding authorisations for the same active substance — the EU does not assess each MAH’s PSUR separately. Instead it runs a PSUR single assessment procedure (PSUSA): all MAHs for the substance submit on the same data-lock-point schedule set by the EURD list, and a single PRAC rapporteur (or lead member state, depending on authorisation type) assesses all of the submitted reports together and produces one benefit-risk conclusion that applies across every affected authorisation. In broad terms the procedure runs:

• Day 0 — the common data lock point/submission date from the EURD list.
• Around Day 60 — the rapporteur’s preliminary assessment report.
• Around Day 90 — MAHs comment on the preliminary assessment.
• Around Day 120 — PRAC adopts its recommendation.
• Around Day 134 — CHMP opinion (centrally authorised products) or CMDh position (nationally authorised products), which then becomes binding across the EEA.

Because the outcome applies to every authorisation of the substance regardless of which MAH’s data drove the finding, an individual MAH cannot opt out of a PRAC recommendation — a labeling change or risk-minimisation requirement arising from PSUSA applies to its product even if its own submitted PSUR raised no new signal. This is the practical reason PSUR/PBRER preparation for a multi-source substance is coordinated activity: MAHs sharing a substance typically align on data-lock-point interpretation and, where a pharmacovigilance agreement exists between them, on how underlying case data is reconciled before each submits.

Frequently asked questions

Is a PSUR the same submission as a PBRER?

Yes, within ICH-harmonised jurisdictions. “PBRER” is the name ICH gave the report format in E2C(R2); “PSUR” is the older name that EU legislation still uses for the same document, built to the same E2C(R2) structure.

Who sets the PSUR data lock point for an EU-authorised product?

The EMA’s EURD list sets the data lock point and submission date for each active substance, overriding the generic ICH default interval (6-monthly, then annual, then 3-yearly from the international birth date) on a per-substance basis.

How is a PSUR/PBRER different from a DSUR?

A Development Safety Update Report (DSUR), defined in ICH E2F, is the pre-approval aggregate safety report prepared during clinical development. A PSUR/PBRER is the post-approval aggregate report prepared once a product is authorised and marketed. A product can transition from DSUR to PSUR/PBRER reporting as it moves through approval, and a MAH may still owe a DSUR for an indication still in development even after a PSUR/PBRER cycle has started for an approved indication.

Does the single assessment procedure apply outside the EU?

PSUSA is specifically an EU mechanism, run by PRAC/CHMP/CMDh under EU pharmacovigilance legislation. Other ICH regions generally assess each MAH’s submission independently, though they use the same E2C(R2) report format.

Related: Pharmacovigilance in Clinical Research: AE, SAE, and SUSAR Reporting covers individual case safety reporting during trials, which feeds into (but is distinct from) the aggregate PSUR/PBRER process. Good Pharmacovigilance Practices (GVP) explains the broader EU regulatory framework PSUR obligations sit inside. Pharmacovigilance System Master File (PSMF) is the organisational document describing the MAH’s pharmacovigilance system as a whole, distinct from any single periodic report. Pharmacovigilance Certification covers professional credentialing for staff who prepare these submissions.