1. Periodic Safety Update Reports (PSUR)
Julien LAURENT
15/11/2016

2. Definitions Periodic safety update report (PSUR)
“Format and content for providing an evaluation of the risk-benefit balance of a medicinal product for submission by the marketing authorization holder at defined time points during the post- authorization phase”
Objective of the PSUR is to present a comprehensive and critical analysis taking into account new or emerging safety information
The main objective of a PSUR is to present a comprehensive, concise and critical analysis of the risk-benefit balance of the medicinal product taking into account new or emerging information, in the context of cumulative information, on risks and benefits. The PSUR is therefore a tool for post-authorisation evaluation at defined time points in the lifecycle of the product.
Guideline on good pharmacovigilance practices (GVP) Annex I - Definitions (Rev 3) EMA/876333/2011

3. Legal Framework Products authorised through national procedure
(MRP, DCP, Purely National Authorization)
Directive 2001/83/EC amended by Directives 2010/84/UE and 2012/26/UE
Title IX Articles 101 to 108: Pharmacovigilance requirements
Articles 107b to 107g
Products authorised through centralised procedure
Regulation (EC) No 726/2004 amended by Regulation 1235/2010 and 1027/2012
Title II Ch. 3 Articles 21 to 29: Pharmacovigilance requirements
Good pharmacovigilance Practices (GVP)
Module VII – Periodic safety update report

4. Responsibilities: EMA
Coordination of the pharmacovigilance and monitoring of the safety concerns
Maintain a list of products subject to additional monitoring
Maintain repository of PSUR and coordinate their assessment
PRAC
Frequency of submission of PSUR
Recommendations after reviewing the PSUR
CHMP
opinions based on PRAC recommendations
(For CAP)
CMDh
positions based on PRAC recommendations
(For NAP)

5. National Competent Authorities Marketing Authorization Holders
Responsibilities
National Competent Authorities
Marketing Authorization Holders
Record, interpretation and verification of all pharmacovigilance information
Preparation and submission of periodic safety update reports
Taking necessary measures with respect to authorizations as a result of the evaluation of PSURs

6. Content of PSUR (1/2) In general each PSUR must contain:
Summaries of data relevant to the benefits and risks of the product, including results of all studies with a consideration of their potential impact on the product’s authorization
A scientific evaluation of the risk-benefit balance of the product; this must be based on all available data including data from clinical trials conducted outside of the terms of the product’s authorization
All data relating to the volume of sales of the product and any data the MA holder has relating to the volume of prescriptions, including an estimate of the population exposed to the product.
(Regulation (EC) No 726/2004 A.28(2); Directive 2001/83/EC A.107b(1))

7. Content of PSUR (2/2) When relevant the PSUR can include:
Need for changes and/or actions expressed by the MA holders
Implications of those changes for the approved product information
Proposals for additional risk minimization activities incorporated in the pharmacovigilance or risk management plans

8. Concerned products All products authorised via:
Centralised procedure
Mutual Recognition Procedure
Decentralised Procedure
Purely national procedure
Not usually required for:
Generic
Well-established use
Homeopathic
Traditional use herbal medicinal products
However, an authority may require PSURs where a specific safety concern has been established or due to the lack of PSURs relating to the active substance (R.28(2); D107b(3)). In such cases the requirement will be specified in the marketing authorisation or included in the EU reference dates list (Section )/ PSUR worksharing list (Section ).
Well known effects
Safety monitored by adverse reaction reporting

9. Frequency of submission
Frequency of submission specified in the marketing authorization
(Regulation (EC) No 726/2004 A.9(4)(aa), 28(2); Directive 2001/83/EC A.107c(1))
Competent authority can request the submission of a PSUR at any time
(Regulation (EC) No 726/2004 A.28(2); Directive 2001/83/EC A. 107c(2))
3 derogations to the general principle
Standard Submission schedule
PSUR work sharing list
EU reference dates (EURD) list  Only list available in short term

10. EU reference dates list (EURD List)
Mandatory since 1-Apr-2013 for NAP and CAP
EU single assessment procedure (PSUSA) performed for all active substances included in the EURD list
Harmonise data lock points (DLPs) and frequency of submissions of PSURs for medicinal products containing the same API or the same combination of API, subject to different MA and authorised in more than one MS
Overrules any conditions related to the frequency of submission of PSURs (marketing authorisation and the standard submission schedule)
Delay for submission after the DLP:
Interval up to 12 months  70 days
Interval in excess of 12 months  90 days

11. EU reference dates list (EURD List)
Data Lock Point
Publication Date
Procedure Number
PRAC Representative
Submission frequency
Submission Date
EURD = Date of the first MA

12. Submission of PSUR: PSUR Repository
Structure of the PSUR is defined in the ICH-E2C (R2) guideline and in the GVP Module VII
CAP  eCTD format
NAP  eCTD or NeeS format
Submission via the eSubmission Gateway or eSubmission Web Client using the XML delivery file
PSUR Repository
Storage place for PSURs and the corresponding assessment reports
Mandatory since 13-Jun-2016
Module of the dossier: Post Marketing Experience

13. EU Single Assessment Procedure (1/2)
Start of procedure
60 D
Assessment Report by PRAC or MS
30 D
Comments from MA Holders or MS
15 D
Upd ated assessment report
Next PRAC Meeting
PRAC Recommendation
Recommendations: Maintenance, Variation, Suspension or Revocation of the MA
Regulatory action required?
Yes No
PRAC Recommendation to CHMP or CMDH
End of the procedure

14. EU Single Assessment Procedure (2/2)
No CAP
Includes CAP
PRAC Recommendation to
CHMP or CMDh
30 D
30 D
CMDh Position
CHMP Opinion
Consensus
No Consensus
Non CAP
CAP
Agreed position to MS
Majority Position to Commission
Commission Decision on
measures to be taken by MS
30 D
National Implementation
Commission Decision to update MA

15. Thank you for your attention
Any questions?