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

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

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

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)

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

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))

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

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 6.11.4.2)/ PSUR worksharing list (Section 6.11.4.3). Well known effects Safety monitored by adverse reaction reporting

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

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

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

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 5.3.6 of the dossier: Post Marketing Experience

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

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

Thank you for your attention Any questions?