Periodic Safety Update Reports (PSURs) are documents submitted by marketing authorization holders to provide an evaluation of a medicine's risk-benefit balance at defined intervals during the post-authorization phase. PSURs must be submitted within 70 or 90 calendar days depending on the interval and contain information on emerging safety issues, benefit-risk analyses, risk management plans, and sources of safety data. The European Medicines Agency publishes the European Union Reference Dates list which mandates the submission timelines and frequencies for PSURs of specific medicines. A single assessment of PSURs is conducted for medicines with the same active substance.
2. Definition
• 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
authorisation holders at defined time points during the post-
authorisation phase. (GVP ModuleVII)
• MAHs responsibility to submit PSURs at defined time points.
• PSURs summarizes the benefits and risks of medicine.
• Evaluation of the benefit-risk balance.
4. What should a PSUR contain??
• The emerging information - new signals, any identified/ potential
risks etc.
• The summary of safety and efficacy information of the medicine.
• An integrated benefit-risk analysis for all authorised indications.
• The summary of any Risk minimization measures.
• The outline plans for signals or risk evaluations.
6. Sources of safety information
• Active surveillance systems
• Clinical trial data
• Competent authorities updates and websites publications.
• Non-clinical studies updates.
• Spontaneous reports, scientific literature/reports, unpublished
manuscripts.
• Post authorisation use in special populations.
7. Content and Format
•Part 1:Title page including signature
•Part 2: Executive Summary
•Part 3:Table of Contents
8.
9.
10.
11. Timelines
• within 70 calendar days PSURs intervals up to 12 months.
• within 90 calendar days - if in excess of 12 months;
• timeline for ad hoc PSURs requested by CA – timeline will be
provided by CA or else 90 days.
12. EURD list
• The European Medicines Agency (EMA) publishes the list of
European Union reference dates and frequency of submission of
PSURs which is known as the ‘EURD list’.
• MAHs submit PSUR mandatorily to NCA - EURD list
• It’s a live document and is amended in a frequency of monthly
(generally)
13.
14. EURD list - Generics
• Generics - Article 10(1) waived to submit PSURs.
• The submission shall be performed as indicated in the EURD list
(Column H for generics).
• Hybrid products – Article 10 (3): PSUR submission not considered
as per the column “H” of the EURD list.
15. PSUR submissions
• As of June 2016, MAHs are required to submit all PSURs in the EU
to the central PSUR repository.
• Use of the PSUR repository is mandatory – single assessment or
National procedure.
• A single assessment of related PSURs is carried out for medicines
that contain the same active substance or combination of active
substances, as per EURD list.
18. Outcome of PSUR Assessment
• A single assessment – published as PSUSA report.
• The outcomes of centrally authorised medicinal products
(CAPs) - European public assessment report (EPAR).
• The outcome of nationally authorised medicinal products
(NAPs) - Community register.
20. References
• GVP module : Guideline on good pharmacovigilance
practices (GVP) ModuleVII – Periodic safety update report
(Rev 1)
• EMA website:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/H
ome_Page.jsp&mid=
Editor's Notes
Marketing-authorisation holders must submit PSURs at defined time points following a medicine’s authorisation.
PSURs summarizes the benefits and risks of a medicine during a scheduled time interval.
PSURs are reports providing an evaluation of the benefit-risk balance of a medicine.
The emerging information during the reporting interval such as new signals, any identified/ potential risks.
The summary of the safety and efficacy information of the medicine during reporting interval.
An integrated benefit-risk analysis for all authorised indications based on the cumulative information available since the development international birth date (DIBD)
The summary of any Risk Minimization Measures (RMM) implemented during reporting period.
The outlining plans for signals or risk evaluations including timelines or proposals for additional pharmacovigilance.
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); and
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.
It is mandatory for the MAHs to submit PSURs to the National Competent Authorities (NCA) according to the dates published in the EURD list.
It’s a live document, and is amended whenever considered necessary by the PRAC, CHMP or CMDh in response to any emerging safety information.
MAH for medicinal products authorised under Article 10(1) of Directive 2001/83/EC has been waived of to submit PSURs, unless there are specific requirements in the MA for the product.
Medicinal products authorised under Article 10(3) of Directive 2001/83/EC (hybrid application) are not exempted from the obligation to submit PSURs.
As of 13 June 2016, MAHs are required to submit all PSURs in the EU to the central PSUR repository using the eSubmission Gateway/ Web Client.
Use of the PSUR repository is mandatory for both centrally and nationally authorised medicines, whether they follow the EU single assessment or a purely national assessment procedure.
Use of the PSUR repository is mandatory for both centrally and nationally authorised medicines, whether they follow the EU single assessment or a purely national assessment procedure.
A single assessment of related PSURs is carried out for medicines that contain the same active substance or combination of active substances, as included in the list of EU reference dates (EURD list)
A single assessment of related PSURs is carried out for medicines that contain the same active substance or combination of active substances as per the EURD list and published as PSUSA report.
The outcomes of PSUR assessments for active substances found only in centrally authorised medicinal products are published as part of each medicine's European public assessment report (EPAR).
The outcome for the nationally authorised medicinal products (NAPs) included in 'mixed' procedures where centrally authorised products were also involved can be found on the Community register.