“Regulatory writing department at Turacoz have the expertise to develop various regulatory documents such as Investigator Brochures (IBs), Protocols, Clinical Study Reports (CSRs), Common Technical Documents (CTDs) and pharmacovigilance documents such as Periodic Safety Update Reports (PSURs) and Risk Management Plans (RMPs). In these slides, we have presented an overview on Periodic safety update reports (PSURs) and also the guidelines such GVP modules and ICH E2c. We have also discussed the changes from old PSUR format to new Periodic Benefit-Risk Evaluation Report (PBRER) format.”

1. Periodic safety update reports – GVP
guidelines and changes
Prepared by:
Amanpreet Singh Kohli
Assistant Manager- Medical affairs
Turacoz Healthcare solutions

2. Table of content
Overview Regulatory Guidelines
Good Pharmacovigilance Practices Content of PBRER/PSUR
Changes to PSUR
01 02
03 04
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3. Overview
• Periodic safety update reports (PSURs) are pharmacovigilance documents intended to provide an evaluation
of the risk-benefit balance of a medicinal product for submission by marketing authorization holders (MAHs)
at defined time points during the post-authorization phase.
• Objective
– to present a comprehensive, concise and critical analysis of the risk-benefit balance of the medicinal product
– a tool for post-authorization evaluation at defined time points in the lifecycle of a product.
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4. Overview (contd.)
• Principle of preparation
– One PSUR for one active substance (all pharmaceutical forms; exceptions possible)
– Use summaries of case narratives instead of the whole CIOMS text
– Take into account new or emerging information in the context of cumulative information on risks and benefits, i.e.
Include both interval and cumulative data
• Timelines
Each MAH shall be responsible for submitting PSURs for its own products according to the following timelines with respect
to DLP :
– within 70 calendar days for PSURs covering intervals up to 12 months (including intervals of exactly 12 months);
– within 90 calendar days for PSURs covering intervals in excess of 12 months;
– ad hoc PSURs requested by competent authorities will normally be specified in the request, otherwise the ad hoc
PSURs should be submitted within 90 calendar days
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5. Regulatory Guidelines
• ICH guideline E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER) (step 5 Dec 2012)
• Guideline on Good Pharmacovigilance Practices (GVP) Module VII (revision 1, 9 Dec 2013) - supersede vol 9A
• As the PSUR should be a single stand–alone document for the reporting interval, based on cumulative data,
summary bridging reports (SBRs) and addendum reports (ARs), introduced in ICH-E2C(R1) guideline, will not
be accepted
– PSUR based on old E2C (R1) format only included the reporting period data with no cumulative information arising
the need for SBRs and ARs
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6. Good Pharmacovigilance Practices
• The good pharmacovigilance practice (GVP) guidelines came into effect in July 2012 to facilitate the
performance of Pharmacovigilance (PV) in the EU.
• The GVP guidelines are divided into 16 modules, each covering a major process in PV. Module VII discusses
changes to the format and content of the PSUR.
• There is no longer a routine requirement for PSURs for generic, well established, homeopathic and herbal
products (exceptions: if a risk is identified or if there is a lack of information).
• The European Medicines Agency (EMA) generates a list of EU reference dates and frequency of
submission. This list is displayed on the EMA web-portal and is expected to be updated monthly.
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7. GVP modules
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8. Content of PBRER/PSUR
Title Page
Executive Summary
Table of Contents
1. Introduction
2. Worldwide Marketing Approval 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
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 Period
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 08

9. 8. Findings from Non-Interventional Studies
9. Information from Other Clinical Trials and Sources
10. Non-Clinical Data
11. Literature
12. Other Periodic Reports
13. Lack of Efficacy in Controlled Clinical Trials
14. 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 Characterization of Risks
16.5 Effectiveness of Risk Minimization (if
applicable)
17. Benefit Evaluation
17.1 Important Baseline Efficacy/Effectiveness
Information
17.2 Newly Identified information on
Efficacy/Effectiveness
17.3 Characterization of Benefits
18. Integrated Benefit-Risk Analysis for Approved
Indications
18.1 Benefit-Risk Context - Medical Need and
Important Alternatives
18.2 Benefit-Risk Analysis Evaluation
19. Conclusions and Actions
20. Appendices
Content of PBRER/PSUR (Contd.)
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10. Changes to PSUR
The following are the important changes in the new format PSUR (PBRER) based on ICH E2C (R2) compared to
old format PSUR based on ICH E2C (R1):
• Risk-benefit analyses:
– Risk evaluation: signals (new, ongoing or closed), evaluation of risks and new information, and effectiveness of
risk minimization activities.
– Benefit evaluation: important baseline efficacy/effectiveness, evaluation of efficacy/effectiveness and new
information.
– Integrated risk-benefit analysis.
• Summary tabulations
– The detailed adverse drug reaction (ADR) line listings will be replaced by more concise cumulative summary
tabulation of serious adverse events from clinical trials and cumulative and interval summary tabulations of ADRs.
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11. Changes to PSUR (contd.)
• Modular approach: The PSUR now has a modular format, which is intended to maximize efficiencies between
different document types, since the same modules can be used in different documents
– PSUR vs. Development Safety Update Report (DSUR): These documents share a number of common sections –
synchronization of submission schedules for these documents should facilitate the use of common text.
– PSUR vs. Risk Management Plan (RMP): Certain PSUR and RMP sections can be used interchangeably across
reports.
• Detailed analyses of cases for special populations (e.g. pregnant/lactating women; organ-impaired patients;
pediatric/elderly patients) is no longer required, unless being assessed as a potential risk.
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12. Possible common sections between PSUR and
RMP
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