Who is Who and What is What in EU Pharmacovigilance

1. Who is Who and What is What in EU Pharmacovigilance Vicki Edwards QPPV and Head of Affiliate Vigilance Excellence AbbVie

2. Overview • European Commission • European Medicines Agency (EMA) • CHMP • PRAC • Competent Authorities of Member States (CAs) • Marketing Authorisation Holder (MAH) • CIOMS • ICH Who’sWho

3. European Commission • Pharmaceutical industry under the responsibility of DG SANCO (Directorate-General for Health and Consumer Affairs) • Competent Authority for Centrally Authorised Products • Drafts proposals for new European Laws • Presents to the European Parliament & Council • Implements the decisions of Parliament & Council • Enforcement of implementation of Decisions by Member States and MAHs • Manages the day to day business of the EU • Runs the programmes of the EU • Spends the EUs funds….. Who’sWho

4. The EU Decision-Making Process • The EU’s decision-making process involves three main institutions • The European Parliament (EP), which represents the EU’s citizens and is directly elected by them. • The Council of the European Union, which represents the individual Member States. • The European Commission, which seeks to uphold the interests of the Union as a whole. • This ‘institutional triangle’ produces the policies and laws that apply throughout the EU. In principle, it is the Commission that proposes new laws, but it is the Parliament and Council that adopt them. European Parliament (EP) Council of the European Union European Commission (EC) Who’sWho

5. European Medicines Agency • Protection and promotion of public health through evaluation and supervision of medicines • Responsible for scientific evaluation of applications for MA for medicinal products (Centralised procedure) • Opinion presented to Commission for decision • Utilises scientific resources of 30 EU and EEA-EFTA countries Who’sWho

6. Role of the EMA • Monitors the safety of medicines through the EU PV network • Takes appropriate action in the event of change to benefit : risk profile of a product • Provides scientific advice to academia and the Pharmaceutical Industry • Provides guidelines on quality, safety and efficacy Who’sWho

7. Role of the EMA • Coordination of the supervision of products authorized in the EU • Monitor legal obligations of MAH • Transmission of Serious ADRs reports between Member States and to Rapporteur • Identify safety signals, in agreement with Rapporteur • Communication of Safety Issues (all parties) • Communication of Opinions to the European Commission • Communication with the MAH in consultation with Rapporteur • Development and maintenance of Eudravigilance database Who’sWho

8. Committee for Medicinal Products for Human Use (CHMP) • Prepares EMA’s opinions on all questions concerning medicinal products • Centrally approved products • Assessment of MAAs and maintenance including modifications and extensions (variations) • MRP & decentralised products • Provides arbitration in event of Member State disagreement • Monitoring of safety of products through EU network of national medicines agencies Who’sWho

9. Co-ordination Group for mutual recognition and decentralised procedures – Human (CMDh) • Examines any question related to marketing authorisations of a medicinal product in two or more member states • New applications • Variations • Renewals • PV activities Who’sWho

10. New Pharmacovigilance Risk Assessment Committee PRAC • Regulation (EU) No 1235/2010 the Mandate shall cover: All aspects of the risk management of the useof medicinal products including the detection, assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to the therapeutic effect of the medicinal product, the design and evaluation of post-authorisation safety studies and pharmacovigilance audit

11. Appointed by each MemberState 1 member + alternate 27 + EEA countries non-votingmembers Appointed by the European Commission (public call for expressions of interest): 1 patient organisationsrep +alternate1 healthcare professionalsrep +alternate6 members to ensure relevant expertise available PRAC Membership

12. Activity Involvement Identified PRAC Activities (1/2) Agreement on RMPs + Monitoring their effectiveness Risk Management Systems List of harmonised submission frequencies and substances, assessment + recommendation Periodic Safety Update ReportsPSURs Eudravigilance + Periodic SafetyUpdate Reports repository Functional specifications, any substantial changes Medicines subject to additional monitoring Addition to/removal from list extension of timeframe, symbol Initial analysis + prioritisationassessment + recommendations Signal detection

13. Activity Involvement Identified PRAC Activities (2/2) Assessment, public hearings, recommendations Urgent Safety Proceduresfor the EU Consultations on requests (pre and post MA), assessment of protocols (incl. amendments +Recommendations, assessment ofresults + Recommendations Post Authorisation SafetyStudies Consultation on list of activesubstances and medical literature subject to monitoring Literature Adverse DrugReactions monitoring Safety announcements Advice

14. PRAC Agenda Issues – All items Proposed PRAC Statistics

15. Signal Overview PRAC outcomes/Signals with NAPs

16. Roles and Responsibilities of the Competent Authorities • Establish national pharmacovigilance systems • Responsible for PV for all products authorised nationally, including mutual recognition products • Responsible for monitoring centrally authorised products • Ensure data are shared between MS’s and EMA via EudraVigilance network • Inform the Commission, CHMP, EMA and MAH of any relevant actions • Provide serious ADR cases to EMA and MAH • Implement Commission Decision • Power to suspend a product in urgent circumstances Who’sWho

17. PRAC and the other Groups/Committees PRAC CHMP Coordination Group CG Recommendations European Commission Member States www.diahome.org

18. PRAC output with formal decision making phase – at least one CAP PSUR Single Assessment PASS Results Referrals Art.107 & Art.31 & Art 20 Publication on EMA website (Art.26 Regulation) PRAC Recommendation & Assessment Report CHMP No Public justification In line with PRAC Publication on EMA website (Art.26 Regulation) European Commission Decision-making phase MS MAH Commission decision Who’sWho

19. PRAC output with formal decision making phase – NAPs only PSUR Single Assessment PASS Results Referrals Art.107 & Art.31 Publication on EMA website (Art.26 Regulation) PRAC Recommendation & Assessment Report CMDh Yes No Agreement by Consensus Yes No Yes No In line with PRAC In line with PRAC MS Publication on EMA website (Art.26 Regulation) MS MAH MAH Publication on EMA website (Art.26 Regulation) EC CMDh consensus and timetable PRAC AR ± scientific grounds for disagreement CMDh consensus and timetable PRAC AR ± scientific grounds for disagreement Commission decision Who’sWho

20. Roles and Responsibilities of the MAH • Ensure an appropriate system of pharmacovigilance and risk management • Provide description at application of MA (DDPS) • Assure responsibility and liability for marketed products • Ensure appropriate action can be taken, when necessary • Immediately notify the Competent Authorities of any change in the balance of risks and benefits of their products • Appoint a Qualified Person Responsible for Pharmacovigilance (QPPV) • Submit proof that the services of the QPPV are available at application of MA • MAH should adequately support the QPPV • Ensure mechanisms are to keep QPPV fully informed • Ensure that the QPPV has sufficient authority Who’sWho

21. Council for International Organisations of Medical Sciences (CIOMS) Who’sWho

22. What is CIOMS • International, non-governmental, non-profit organisation • Established in 1949 by WHO and UNESCO • A forum to consider and prepare advice on contentious issues in research ethics and safety of pharmaceuticals for WHO, public health authorities, academia, pharmaceutical industry and others • Comprises various working groups • Modus operandi = Think Tank (practical solutions) • Think beyond local practices and regulations => optimise drug safety procedures internationally • Do not develop regulations but intended to inform and encourage those with rule-making responsibilities Who’sWho

23. CIOMS Safety Working Groups I Who’sWho

24. CIOMS Safety Working Groups II Who’sWho

25. International Conference on HarmonisationICH – Basic Principles • Development of scientific consensus through discussions between regulatory & industry experts. • Regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration. • Wide consultation of the draft consensus document, through normal regulatory channels, before a harmonised text is adopted. • Commitment by regulatory parties to implement the ICH harmonised texts. Who’sWho

26. ICH Process • Technical discussions in GPS/development of consensus • Consensus achieved with release for consultation • Formal consultation outside ICH • ICH guideline finalized • Implementation in ICH regions Step 1 Step 2 Step 3 Step 4 Step 5 Who’sWho

27. CIOMS, ICH and International Regulation Who’sWho

28. Any Questions? Who’sWho