Periodic safety update reports – GVP guidelines and changes

Prepared by:

Amanpreet Singh Kohli

Assistant Manager- Medical affairs

Turacoz Healthcare solutions

Table of contentOverview Regulatory Guidelines

Good Pharmacovigilance Practices Content of PBRER/PSUR

Changes to PSUR

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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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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 04

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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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

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Content of PBRER/PSUR

Title PageExecutive SummaryTable of Contents1. Introduction2. Worldwide Marketing Approval Status3. Actions Taken in the Reporting Interval for

Safety Reasons4. Changes to Reference Safety Information5. Estimated Exposure and Use Patterns

5.1 Cumulative Subject Exposure in Clinical Trials5.2 Cumulative and Interval Patient Exposure from Marketing Experience

6. Data in Summary Tabulations

6.1 Reference Information6.2 Cumulative Summary Tabulations of Serious Adverse Events from Clinical Trials6.3 Cumulative and Interval Summary Tabulations from Post-Marketing Data Sources

7. Summaries of Significant Findings from Clinical Trials during the Reporting Period7.1 Completed Clinical Trials7.2 Ongoing Clinical Trials7.3 Long-Term Follow-up7.4 Other Therapeutic Use of Medicinal Product7.5 New Safety Data Related to Fixed Combination Therapies

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8. Findings from Non-Interventional Studies9. Information from Other Clinical Trials and

Sources10. Non-Clinical Data11. Literature12. Other Periodic Reports13. Lack of Efficacy in Controlled Clinical Trials14. Late-Breaking Information15. Overview of Signals: New, Ongoing, or Closed16. Signal and Risk Evaluation

16.1 Summary of Safety Concerns16.2 Signal Evaluation16.3 Evaluation of Risks and New Information16.4 Characterization of Risks

16.5 Effectiveness of Risk Minimization (if applicable)

17. Benefit Evaluation17.1 Important Baseline Efficacy/Effectiveness Information17.2 Newly Identified information on Efficacy/Effectiveness17.3 Characterization of Benefits

18. Integrated Benefit-Risk Analysis for Approved Indications18.1 Benefit-Risk Context - Medical Need and Important Alternatives18.2 Benefit-Risk Analysis Evaluation

19. Conclusions and Actions20. Appendices

Content of PBRER/PSUR (Contd.)

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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; organ-impaired 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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