1. Pharmacovigilance Risk Assessment Committee (PRAC): Nye tider – nye opgaver Doris I. Stenver Overlæge, medlem af PRAC

2. Pharmacovigilance Risk Assessment Committee (PRAC): Nye tider – nye opgaver Doris I. Stenver Overlæge, medlem af PRAC

3. 3 Overview  New pharmacovigilance legislation – purpose and expected achievements  Pharmacovigilance Risk Assessment Committee – tasks and responsibilities  EMA Implementation plan  GVP modules – status  Commission Implementing Regulation  Revision of legislation

4. 4 Ancient times…..

5. 5 Impact of thalidomide tragedy in the 1960s  Establishment of drug safety surveillance systems  Involvement of health professionals  Decisions based on national experience  Non-transparent environment

6. 6 European Medicines Agency London, since 1995 www.ema.europa.eu

7. 7 Present time…..  Internet era  Transparency  Internationalisation  Competitive power  Innovative power  Disease burden  Involvement of patients

8. 8 New pharmacovigilance legislation  In general, overall strengthening of pharmacovigilance  Clear roles and responsibilities  Rational use of ressources  Streamlined procedures (administrative and scientific) with timetables  New ADR definition  New PSUR format and scope  Legal basis for PASS  Transparency  HCP & Patient involvement

9. 9 8 Pharmacovigilance – basic steps Risk detection / signal detection Risk assessment Risk and therapeutic effect assessment Communication of risk and benefit/risk Risk minimisation (regulatory action) and analysis of impact of risk minimisation Pharmacovigilance audit Design and Evaluation of post authorisation safety studies

10. 10 PRAC tasks and responsibilities  Referral procedures for safety reasons  Signals detected from EU spontaneous reporting systems  Risk management plans  PSUR assessments  Post-Authorisation Safety Studies (PASS)  Product-related pharmacovigilance inspections  Safety issues – requested by CHMP or by MS(s)  Organisational, regulatory and methodological matters

11. 11 PRAC agenda September 2012  Referral procedures for safety reasons: None  Signals detected: Thirteen  Risk management plans: One  PSUR assessments: None  Post-Authorisation Safety Studies (PASS): None  Product-related pharmacovigilance inspections: Two  Safety issues – requested by CHMP or by MS(s): None  Organisational, regulatory and methodological matters: Many

12. 12 PRAC agenda September 2012 – new signals  4.1.10. Varenicline - CHAMPIX (CAP)  Signal of seizures  Status: for initial discussion  Regulatory details:  PRAC Rapporteur: Doris Stenver (DK)

13. 13 PRAC recommendation flow Coordination Group CG CHMP European Commission Member States PRAC Recommendations

14. 14 PRAC agenda September 2012 – new signals  4.1.8. Somatropin – NUTROPINAQ, OMNITROPE (CAPs, NAPs)  Signal of convulsions (SMQs – Standardised MedDRA Queries)  Status: for initial discussion and Rapporteur appointment  Regulatory details:  PRAC Rapporteur: to be appointed

15. 15 PRAC agenda September 2012 - inspections  8.2. On-going or concluded pharmacovigilance inspections  Disclosure of information on results of pharmacovigilance inspections could undermine the protection of the purpose of these inspections, investigations and audits. Therefore such information is not reported in the agenda.

16. 16 PSUR Single Assessment – EURD list (11.3.3)  EU Reference Date List for > 3.300 products  Compiled by EMA, based on EVMPD, PSUR WS and Synchronisation lists  4 consultations with MSs  PRAC consultation September 2012  CHMP & CMD(h) consultation / agreement September 2012  Publication by 30 th September – simultaneously with list on signal WS; becomes binding in April 2013  Monthly updates – dynamic EURD  Process for maintenance under discussion

17. 17 Not all is written in stone!

18. 18 Appointment of PRAC Rapporteurs  Guiding principles – best possible and available expertise, knowledge continuity, “fresh pair of eyes”  Legacy medicines – open up for PRAC rapporteurships to all PRAC delegates  New MAAs – PRAC co-Rapporteur from same MS as CHMP Rapporteur  Gradual phasing in from 4Q2012 in relation to all CAPs due for PSUR assessments of PASS results evaluation in 1Q2013;  Referrals – only non-CAPs  Rapporteur: open to all PRAC delegates  Co-Rapporteur: triggering MS  Referrals – mixture of CAPs and non-CAPs  Rapporteur: PRAC rapporteur for the CAPs  Co-Rapporteur: triggering MS

19. 19 EMA Implementation Plan February 2012  Launched 1 February  Activities in 2012 and beyond 2012 (budget and ressource restrictions)  Activities contributing to public health highest priority, followed by those increasing transparency and improving communication, and with lowest priority those that simplify procedures  4 main topic areas  Collection of key information on medicines  Better analysis and understanding of data and information  Regulatory action to safeguard public health  Communication with stakeholders

20. 20 Collection of key information on medicines  Risk Management Plans (RMPs) (GVP-V)  Strenghtened procedures for submission; beyond 2012 establishment of a risk management effectiveness monitoring system  Periodic Safety Update reports (PSURs) (GVP-VII)  Benefit-Risk evaluation tool; new procedures for submission (CAPs), list of Union reference dates; beyond 2012 focus on PSURs for NAPs  Post-authorisation safety and efficacy studies (PASS/PAES) (GVP-VIII)  Require and enforce PASS/PAES; scientific GL to support delegated act on criteria for PAES

21. 21 Collection of key information on medicines  Electronic submission of core medicine information by pharmaceutical industry (art. 57 requirements)  Extensive requirements – Yes! But in order to conduct effective SD on data in Eudravigilance a comprehensive drug dictionary is a basic requirement; revised legal notice in febr. 2012  Reporting by patients  Information to be provided on this new opportunity

22. 22 Better analysis and understanding of data and information  Eudravigilance and Signal Detection  Revised SD process for CAPs; improved access to data on NAPs; improvement of data quality ongoing  Additional Monitoring  First list of medicines subject to additional monitoring  IT systems to support processing and analysis of data  Full development of new IT systems will not begin until after 2012

23. 23 Regulatory action to safeguard public health  Scientific committees and decision-making  Pharmacovigilance Risk Assessment Committee (PRAC) inaugural meeting 19 July 2012 (Bruxelles)  CMD(h) strengthened mandate – will lead on decision- making based on PRAC recommendations  Opinion-making power by either consensus or majority vote  legally binding EC decisions

24. 24 Regulatory action to safeguard public health  Strengthening referral procedures  Urgent Union Procedure  Designed to address significant emerging safety issues with a medicine available in the EU, regardless of authorisation procedure  Systematic involvement of PRAC in providing safety expertice for assessment and to identify appropriate regulatory actions, for subsequent adoption by CHMP or CMD(h)  Increased transparency (publication of information and public hearings)

25. 25 Communication with stakeholders  Publication of  Agendas, minutes, assessments, recommendations and opinions  Scope – PRAC, CMD(h), CHMP  Coordination of safety anouncements  For nationally authorised products  Ensure consistent and coherent safety advice across Europe  Public hearings  In relation to referrals within the Urgent Union Procedure

26. 26 Good Pharmacovigilance Practices (GVP)  GVP Modules – 1 st wave: FINAL June 2012  I PhV Systems and their Quality Systems  II PhV System Master File  V Risk Management Systems  VI Individual Case Safety Reports  VII Periodic Safety Update Reports  VIII Post-Authorisation Safety Studies  IX Signals

27. 27 Good Pharmacovigilance Practices (GVP)  GVP Modules – 2 nd wave: Ongoing  III Audits Public Consultation until 21 September 2012  IV Inspections Public Consultation closed; time table for finalisation awaited  X Additional Monitoring Public Consultation closed; time table for finalisation awaited  XI Public Participation Drafting ongoing  XII Continuous phv, B/R evaluation, communication planning and decision-making for regulatory action Drafting ongoing  XV Safety Communication Consultation until 21 September 2012  XVI Risk Minimisation Measures Drafting ongoing  XIII Incident management (scope tbc)  XIV International collaboration (scope tbc)

28. 28 Good Pharmacovigilance Practices (GVP)  GVP Considerations for product- and population-specific pharmacovigilance  Biological medicinal products incl. biosimilars  Vaccines (Review drafting ongoing)  Pregnancy  Children  Elderly

29. 29 Commission Implementing Regulation (EU) No 520/2012  I. Pharmacovigilance System Master File  II. Minimum requirements for quality systems  III. Minimum requirements for Eudravigilance database, details on signal management  IV. Terminology, formats, standards  V. Individual Case Safety Reports  VI. Risk Management Plans  VII. Periodic Safety Update Reports  VIII. Post-Authorisation Safety Studies  IX. Final provisions

30. 30 All is written in stone - almost!

31. 31 Revision of legislation  Art. 23 of the Regulation concerning the list of medicinal products subject to additional monitoring  Medicinal products where a PASS is a condition for the MA  Medicinal products approved in exceptional circumstances and subject to specific obligations (art. 14 (7) and (8) REG, art. 22 DIR); MAH with stricter obligations to register / report suspected ADRs  Strengthened obligations for MAHs to inform regulatory authorities about causes underlying withdrawals of medicinal products, request for withdrawal of MA or decision on not to apply for renewal of a MA. MAH shall in particular declare if such actions are based on any of the grounds set out in art. 116 and 117(1) of Directive 2001/83  Art. 107i of the Directive, Urgent Union Procedure  …when urgent action is considered necessary… deleted; Except art. 107i(1), point e (new contraindication, reduction in recommended dose or a restriction to the indications)