Usage Examples
- The DLP is 31 March, so the PBRER has to be with the agency by 9 June.
- We sit on the EURD list at a three-yearly cycle, so this PBRER covers 36 months and gets 90 days.
- Section 16 needs the signal evaluation closed before anyone can write the PBRER executive summary.
What is Periodic Benefit-Risk Evaluation Report (PBRER)?
The Periodic Benefit-Risk Evaluation Report (PBRER) is the ICH E2C(R2) periodic safety report for marketed medicines, distinguished from the earlier PSUR format by a formal evaluation of benefit alongside risk to support an explicit benefit-risk conclusion.
The Periodic Benefit-Risk Evaluation Report exists because a marketing approval is a judgement made on thin data: a few thousand closely monitored patients, narrow inclusion criteria, short follow-up. Once a product reaches ordinary practice, exposure widens and rare events surface. The PBRER forces the marketing authorisation holder to re-argue, at fixed intervals and in writing, that the benefits still outweigh the risks.
The PBRER covers worldwide marketing approval status, safety-driven regulatory actions, changes to reference safety information, cumulative and interval exposure, signal evaluation, benefit evaluation, and an integrated benefit-risk analysis, across twenty numbered sections. The PBRER is not an alerting mechanism. ICH states plainly that it is not the vehicle for initial notification of significant new safety information, which goes through expedited reporting.
The PBRER runs on two dates. The International Birth Date, the first marketing approval for the active substance anywhere in the world, fixes the cycle; the data lock point is the data cut-off and day 0 of a 70- or 90-calendar-day submission clock. In the EU the PBRER is filed as a PSUR, on whatever frequency the EURD list sets for that active substance.
Not to be confused with
- PSUR
- PSUR is the EU's legal name for the periodic report; PBRER is the ICH format that report must follow. Same document, different label depending on who you are filing to.
- PADER
- the US periodic adverse drug experience report under 21 CFR 314.80 is a listing-and-narrative obligation on its own quarterly-then-annual clock. It is a reporting return, not a benefit-risk argument, and a PBRER does not satisfy it by default.
- DSUR
- the Development Safety Update Report covers products still in clinical development and runs off the Development International Birth Date. The PBRER covers marketed products and runs off the IBD; ICH built shared sections so content can move between the two.
- RMP safety specification
- the risk management plan's safety specification is forward-looking, setting out what will be characterised and minimised. The PBRER is backward-looking: what the reporting interval actually produced.
The obligations come from ICH E2C(R2) plus whatever the receiving region layers on top.
What you must do
- 1Present a comprehensive, concise, and critical analysis of new or emerging risk information, and of benefit in approved indications, sufficient to appraise the overall benefit-risk profileICH E2C(R2) Section 1.2
- 2Route urgent safety findings through expedited reporting rather than the PBRER, which is not the vehicle for initial notification of significant new safety informationICH E2C(R2) Section 1.2
- 3Anchor the data lock point to the International Birth Date, the date of first marketing approval for any product containing the active substance in any country in the worldICH E2C(R2) Section 2.8.1
- 4Submit within 70 calendar days of the data lock point for intervals of 6 or 12 months, and within 90 calendar days for intervals over 12 months, counting the DLP as day 0ICH E2C(R2) Section 2.8.3
- 5In the EU, follow the frequency published on the EURD list for the active substance, which overrules the standard 6-monthly, yearly and 3-yearly cycleEU GVP Module VII / EURD list
- 6In the US, keep filing periodic adverse drug experience reports quarterly for 3 years from approval and annually thereafter, unless FDA gives written notice of different timing21 CFR 314.80(c)(2)(i)
Common mistakes
Carrying the benefit section forward unchanged
the formal benefit evaluation is the feature that separates the PBRER from the old PSUR. A reviewer who sees a new important risk in Section 16 sitting next to boilerplate efficacy text in Section 17 has no basis to accept the benefit-risk conclusion in Section 18, and will ask for it again.
Treating the 70 days as starting when the data arrives
the DLP is day 0, not the day the tabulations land on someone's desk. Teams that start the clock at data delivery routinely burn two to three weeks of the window, and because one harmonised DLP drives every region, a single slip makes the report late everywhere at once.
Assuming the default 6-monthly, yearly, 3-yearly cycle holds in the EU
the EURD list frequency overrules it per active substance and gets revised. A team running on the default cycle can be a full year out of step with what is actually required, which is a compliance finding, not a scheduling inconvenience.
When This Matters
- The DLP is 31 March, so the PBRER has to be with the agency by 9 June.
- We sit on the EURD list at a three-yearly cycle, so this PBRER covers 36 months and gets 90 days.
- Section 16 needs the signal evaluation closed before anyone can write the PBRER executive summary.
Frequently Asked Questions
PBRER is the ICH E2C(R2) format; PSUR is the EU's legal name for the same document. The EU requires PSURs whose format and content are based on the PBRER described in ICH E2C(R2), so in practice EU teams write a PBRER and file it as a PSUR.
