PSUR/PBRER (Periodic Benefit Risk Evaluation Report)-Aggregate report in PV

PSUR/PBRER (Periodic Benefit Risk Evaluation Report)

If you ask anyone what they want to do next in PV? Most certainly if they have just started PV career and /or in ICSR the answer is aggregate reports.  

PBRER/PSUR is one important aggregate report. Let’s look at template of PSUR in this blog and sections. PBRER (Periodic Benefit Risk Evaluation Report) and PSUR (Periodic Safety Update Report) are interchangeably used, but the both are different. PSUR is simple template than PBRER accepted by many health authorities and especially for established products.

Below is template of PBRER as per E2C (R2) step 3 Guideline:

Section in PSUR	Name of section
Part I	Title Page
Part II	Executive Summary
Part II	Executive Summary
Part II	Executive Summary
Part II	Executive Summary
1	Introduction
2	Worldwide Marketing Authorization Status
3	Actions Taken In the reporting interval for Safety Reasons
4	Changes to Reference Safety Information
5	Estimated Exposure and Use Patterns
5.1	Cumulative Subject Exposure in Clinical Trials
5.2	Cumulative and Interval Patient Exposure from Marketing Experience
5.3	Post  Approval use in Special Population
5.3	Other post approval use
6	Data in Summary Tabulations
6.1	Reference information
6.2	Cumulative summary tabulations of serious adverse events from clinical trials
6.3	Cumulative and interval summary tabulations from post-marketing data sources
7	Summaries of significant findings from clinical trials during the reporting interval
7.1	Completed clinical trials
7.2	Ongoing clinical trials
7.3	Long-term follow-up
7.4	Other therapeutic use of medicinal product
7.5	New safety data related to fixed combination therapies
8	Findings from non-interventional studies
9	Information from other clinical trials and sources
9.1	Other clinical trials
9.2	Medication errors
10	Non-clinical Data
11	Literature
12	“Other periodic reports”
13	“Lack of efficacy in controlled clinical trials
14	PSUR section “Late-breaking information”
15	“Overview of signals: new, ongoing, or closed
16	Signal and risk evaluation
16.1	Summary of safety concerns
16.2	Signal evaluation
16.3	Evaluation of risks and new information
16.4	Characterisation of risks
16.5	Effectiveness of risk minimisation
17	Benefit evaluation
17.1	Important baseline efficacy and effectiveness information
17.2	Newly identified information on efficacy and effectiveness
17.3	Characterisation of benefits
18	“Integrated benefit-risk analysis for authorised indications
18.1	Benefit-risk context - medical need and important alternatives
18.2	Benefit-risk analysis evaluation
19	Conclusions and actions
20	Appendices to the PSUR

Introduction covers the products details (content, date of first marketing authorisation, formulation etc)

The section regarding worldwide market authorisation status is usually available with regulatory affairs or marketing department. It is regarding the status of approval of the product in different countries. This ensures that there is dialog between PV and regulatory affairs and consequently other affiliates in each country where the product is approved regarding its status. If there was any change in authorisation etc ,PSUR stands as a good check periodically in knowing such changes.

In the next section, there is section wherein such changes in the regulatory status due to actions taken by MAH or actions directed by regulatory authority due to safety reasons are enlisted. One example would be if the product labelling was updated due to safety reasons then this will be included herein.

Changes to safety information section would talk about the changes in the reference safety information section of CCDS,USPI,SmPC or IB.

Patient exposure data is generally available with sales team/marketing department. This data is important to understand the age group (pregnancy/breastfeeding etc) and the total product distributed.

The section 6 is about ICSR, and should provide only summary tabulation. If presenting a case is required usually this are SUSARs (Serious unlisted cases) and Fatal cases in section 16. In case of low volume a decision to include short narrative of all cases can be taken. Overall, good idea is to present only relevant cases of that review period. Presentation of cases is usually in a form of short narrative with only information that is relevant to medical assessment of case.

In the section about studies, data regarding ongoing, completed ,company sponsored or non sponsored studies is evaluated and presented.

The sections about overall safety evaluation is summary of all safety information presented in PSUR and how it affects the safety profile of product. 

The most time consuming section is section of risk and benefit. Characterizing risk is very important step which should be derived from RMP or USPI/SmPC when writing for first time. Usually the idea is to only describe risk that are important identified, potential risk and missing information. The risks definitions and signal definition can be referred in GVP modules. One good starting point is the risks that are mentioned in contraindications, warnings and precautions, and important adverse reactions  ,class actions in potential risk. Not all risk qualify as important, those that have higher severity, impact, risk minimization measures are loosely considered as identified. Writing benefits section will depend on current approved indications and usage and should summaries the current profile of product.

Conclusion will give an presentation regarding if the data in PSUR will led to any action in terms of changing label of product, change in RMP etc.

Generally this PSUR template which is more concise is accepted by rest of the world authorities (Non-EU) E.g. DCGI, Russia ,Malaysia etc and generally for generic products.

Frequency of PSUR: Each regulatory authority has different requirements with respect to timelines of PSUR. As an example for CDSCO -India's regulatory authority below is standard:

 PSURs shall be submitted every six months for the first two years from the approval of product and annually for the subsequent two years, and it must be submitted within 30 calendar days of the last day of the reporting period.

If you are author, compiler or reviewer, in addition to PSUR you need to be aware of baseline safety profile of product, competitors USPI/CCDS, Regulatory status on signals or any communications. You should also have other skills and tool to manage this document- word, time management, project management etc.

I hope, I could summarize key points regarding PSUR in this blog.

Reference:

E2C R2

RMP GVP V

PSUR GVP VII

Written by:

Dr.Shraddha Bhange.

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