Summary of Module VII – Periodic safety update report
Continuing the series on Guideline on good pharmacovigilance practices, in this blog i will jump right into module VI having covered module I , II, III, IV, V and VI in previous blogs.
This module describes the PSUR requirements.
Overall, the module does go in more and clear details on expectations and its best to read module thoroughly and completely when one has to write, compile, review or submit PSUR.
Reference:https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-gvp-module-vii-periodic-safety-update-report_en.pdf
What is PSUR?
It is legally required document for a medicinal product that needs to be submitted by MAH to agency and/or national competent authority after the drug is approved at a set frequency within defined timelines.
The format and content of PSUR is provided in this module and also refers to PBRER format as per the ICH-E2C(R2) guideline.
This is scientific document which compiles the safety data related to the particular medicinal product. Analysis of this safety data in terms of its impact on benefit-risk profile of product.
Why is it written?
To determine whether there are new risks or whether risks have changed or whether there are changes to the risk-benefit balance of medicinal products
When is it written?
Usually PSUR is required for new authorized products or products that are launched recently in new indication or formulation etc. Products for whom safety profile is not yet established. With this background, the PSUR is usually not required for generic or OTC products unless requested by agency or NCA.
The timelines are below as per module.
- within 70 calendar days of the data lock point (day 0) for PSURs covering intervals up to 12 months (including intervals of exactly 12 months);
- within 90 calendar days of the data lock point (day 0) for PSURs covering intervals in excess of 12 months;
- the timeline for the submission of 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 of the data lock point.
How is it written?
The sections along with short expectation for each section is summarized from detailed requirements for each section in module.
Part I: Title page including signature
It should be clear who are the signatories at organizational level. Generally it is head of PV, CMO, Safety physician, medical writer.
Part II: Executive Summary
This section should provide summary of product in terms of indication, review period, analysis of data and its impact on benefit-risk assessment, exposure data. The section is used for wider audience (non-PV) so the aim is to keep it concise and clear.
Part III: Table of Contents (TOC)
As the PSUR is very lengthy documents easy navigation via TOC is mandatory.
Section 1 Introduction
This covers products introduction, review period, patient exposure, disease/indication.
Section 2 Worldwide marketing authorisation status
This is generally presented in tabular format which explains the products status across worlf, IBD, approval country and date.
Section 3 Actions taken in the reporting interval for safety reasons
This includes actions for the product in investigational (clinical trial ) or marketing. The actions alongside reasons should be provided. E.g. Change in RSI (SmPC, USPI), Protocol modifications, suspension, withdrawal, pack size, restriction on use, communication to consumers or HCPs.
Section 4 Changes to reference safety information
Any changes to RSI implemented during the review period i.e. change in warnings, precautions, contraindications etc should be explained.
Section 5 Estimated exposure and use patterns
In this section we use sales data to calculate patient exposure and other data such as from clinical trials. The age group, gender, different usage etc. can also be found from this data for categorization.
Section 6 Data in summary tabulations
This refers to data from safety database. No need to present single ICSR cases, but cumulative assessment. If there are few cases that needs to be described then the narrative should not be copy paste from CIOMS, but clinical assessment of narrative.
Section 7 Summaries of significant findings from clinical trials during the reporting interval
Present the data analysis form each study in terms of new safety information herein. Tabular format of ongoing or completed studies by study ID, indication, age/sex etc can be presented.
Section 8 Findings from non-interventional studies
Aggregate analysis of data and its impact from various non interventional studies such as observational studies, epidemiological studies, registries, and active surveillance programs.
Section 9 Information from other clinical trials and sources
This section should provide pooled aggregate analysis of data from other clinical trials and data on medication errors etc.
Section 10 Non-clinical data
This section will provide analysis and summary of major safety findings from non-clinical in vivo and in vitro studies (e.g. carcinogenicity, reproduction or immunotoxicity studies) ongoing or completed during the reporting interval.
Section 11 Literature
This section will describe the articles that were found to be relevent form the risk-benefit analysis of product.
Section 12 Other periodic reports
If there are other periodic reports developed then summarize finding from that report herein.
Section 13 Lack of effect
13. This
section should summarize data regarding lack of efficacy,
or lack of efficacy especially to product's used treat or prevent serious or life-threatening illnesses.
This is not per se cases received unless they are index case and promoted as signal. This refers to clinically significant new publications, important follow-up data, clinically relevant toxicological findings and any action that the marketing authorization holder, a data monitoring committee, or a competent authority (worldwide) has taken for safety reasons.
Section 15 Overview of signals: new, ongoing, or closed
This section refers to overview of all signal in review period. The signal can be provided as tabulation as well. New signal and their status. Ongoing signal and if any change in its status or relevance. Closed signals and there outcome is presented.
Section 16 Signal and risk evaluation
This should not be repetition of section 15 but rather interpretation of the data on signals. An clinical analysis of signal and how they relate to current risks. An mapping can be provided for the signals to current risks and how they are presented in current RSI or what are risk minimization measures for this risks.
Section 17 Benefit evaluation
This provides baseline efficacy data and effectiveness of product in the approved indication or new indication if the data is found such.
Section 18 Integrated benefit-risk analysis for authorized indications
Summary of benefit risk assessment of the product and conclusion on any planned actions for maintaining the same. How the current benefits and risks are addressed for the product and the data suggests the change or it remains same.
Section 19 Conclusion
- Summary of the data
- Changes or no changes to benefits
- Changes or no changes to risk
- Integration of risk and benefits
- Proposed plan on how to balance the BR e.g. any risk minimization measures
Section 20 Appendices of PSUR
1. RSI
2. ICSR tabulations from safety database
3. Tabular summary of safety signals
4. List of all clinical trials
5. Regional appendices
It is important to note which reference safety is used during PSUR, there are multiple variations given in the module. It is most common to use the RSI that was effective at the end of the review period.
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