What are PBRER and PSUR?

Think of a new medicine as a new employee. For the first few years, you monitor them closely with frequent performance reviews. A PSUR/PBRER is like that comprehensive performance review for a medicine, looking at both its benefits (the good work it does) and its risks (its shortcomings or side effects) to decide if it should stay in the job, if its role needs to change, or if it should be let go.

What are PBRER and PSUR?

Both are periodic, comprehensive reports submitted by pharmaceutical companies to regulatory authorities (like the FDA or EMA) to summarize the safety and benefit-risk profile of a medicine after it has been approved and is on the market.

• PSUR (Periodic Safety Update Report): This was the original term and format. Its primary focus was on the safety of the drug—detailing new adverse events, what was learned about known risks, and the overall safety profile.
• PBRER (Periodic Benefit-Risk Evaluation Report): This is the newer, current standard, introduced by the ICH (International Council for Harmonisation) E2C(R2) guideline. It represents a significant shift in thinking.

The Key Difference: From Safety to Benefit-Risk

Feature	PSUR (Older Focus)	PBRER (Current Focus)
Primary Goal	Summarize safety data.	Evaluate the balance between benefits and risks.
Emphasis	“What are the new safety findings?”	“Do the benefits of the drug still outweigh its risks, given the new data?”
Content	Heavily weighted towards adverse events and safety analyses.	Integrates new safety data with new efficacy/benefit data and existing knowledge for a holistic view.
Outcome	Primarily a safety summary.	A conclusion on the benefit-risk balance and any recommended actions.

In essence, the PBRER doesn’t just list problems; it puts them in the context of the drug’s proven benefits. A drug might have new side effects, but if it is highly effective at treating a serious disease, its benefit-risk profile might still be positive.

Key Purposes of a PBRER/PSUR

1. Provide a Comprehensive Update: It brings together all new safety and efficacy information from a defined period (the “data lock point”).
2. Re-evaluate the Benefit-Risk Balance: This is the core purpose. Is the medicine still acceptable for use in the approved indications?
3. Identify New Safety Signals: Detect any new, potentially concerning patterns of adverse events.
4. Summarize Actions Taken: Report any risk minimization activities taken during the reporting period (e.g., label changes, sending letters to doctors).
5. Inform Regulatory Decisions: Helps regulators decide if the product’s marketing authorization should be maintained, changed, suspended, or revoked.

Structure and Content of a PBRER/PSUR

Section	Content
Introduction	Product details, reporting interval, populations
Worldwide MA Status	Authorization dates, indications, doses
Actions for Safety	Significant safety-related actions taken
Changes to Reference Safety Info	Updates to the Company Core Data Sheet (CCDS)
Estimated Exposure	Clinical trial and post-marketing exposure data
Summary Tabulations	Aggregate data on adverse events/reactions
Clinical Trial Findings	Significant new efficacy/safety data from trials
Non-Interventional Studies	Data from observational studies, registries, etc.
Signals & Risk Evaluation	Overview and evaluation of new and ongoing signals
Benefit Evaluation	Efficacy and effectiveness data
Integrated Benefit-Risk Analysis	Critical appraisal of the overall balance
Conclusions & Actions	Proposed changes to product information or risk minimization

When are they submitted?

The frequency depends on the medicine’s stage in its lifecycle:

• Immediately after approval: Usually every 6 months.
• Later: Moves to annually.
• After several years on the market: May move to a longer cycle (e.g., every 3 years) if the safety profile is well-established and stable.

PSUR Assessment Process in the EU

Single Assessment:

• For products containing the same active substance authorized in multiple Member States, a single PSUR assessment is conducted.
• Led by:
  • PRAC Rapporteur (if at least one product is centrally authorized)
  • Member State (if all are nationally authorized)

Assessment Steps:

1. Technical validation by the EMA.
2. Preliminary assessment report within 60 days.
3. Comments from MAH and PRAC members by Day 90.
4. Updated assessment report by Day 105.
5. PRAC recommendation at the next meeting.
6. CHMP opinion (for centrally authorized products) or CMDh position (for nationally authorized products).
7. European Commission decision or national implementation.

In essence, the PSUR is a critical lifecycle safety monitoring tool that ensures the continued safety of patients by regularly re-evaluating a medicine’s profile in the real world and prompting regulatory action to protect public health.