Periodic safety update reports GVP

guidelines and changes

Prepared by:
Amanpreet Singh Kohli
Assistant Manager- Medical affairs
Turacoz Healthcare solutions

Table of content
01

Overview

02

Regulatory Guidelines

03 Good Pharmacovigilance Practices

04

Content of PBRER/PSUR

05

Changes to PSUR

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 postauthorization 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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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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Regulatory Guidelines

ICH guideline E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER) (step 5 Dec 2012)

As the PSUR should be a single standalone 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

Guideline on Good Pharmacovigilance Practices (GVP) Module VII (revision 1, 9 Dec 2013) supersede vol 9A

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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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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GVP modules

07

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

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Content of PBRER/PSUR (Contd.)

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

09

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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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; organimpaired patients; pediatric/elderly patients) is no longer required, unless being assessed
as a potential risk.

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Possible common sections between PSUR

and RMP

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