Slide 1 November 2008 Name Sarah Morgan © Crown copyright 2005 Pharmacovigilance Working Party - Role and future perspective Sarah Morgan Medicines and Healthcare products Regulatory Agency UK Delegate - PhVWP November 2008

Slide 2 November 2008 Name Sarah Morgan © Crown copyright 2005 Roles of key players National Competent Authorities (NCAs)  operate national systems in member states European Medicines Agency (EMEA)  co-ordinates pharmacovigilance for centralised products (and non-centralised products) Committee for Medicinal Products for Human Use (CHMP)  provides opinions on safety issues with centrally authorised products and other issues as referred

Slide 3 November 2008 Name Sarah Morgan © Crown copyright 2005 Pharmacovigilance Working Party ‘The mission of the PhVWP is to provide advice on the safety of medicinal products authorised in the EU and …recommendations for regulatory action to its stakeholders, i.e. the CHMP/EMEA and NCAs.’

Slide 4 November 2008 Name Sarah Morgan © Crown copyright 2005 EfficacySafetyPhVWPQualityBiotech European Commission CHMP CMD(h) NCAs

Slide 5 November 2008 Name Sarah Morgan © Crown copyright 2005 PhVWP  Chairperson – Dr June Raine, MHRA  1 representative per Member State appointed by NCAs  7 Co-opted members with expertise in pharmacoepidemiology, risk management, biological products/advance therapies, paediatrics, communications

Slide 6 November 2008 Name Sarah Morgan © Crown copyright 2005 PhVWP's responsibilities  evaluation of potential signals arising from spontaneous reporting  provision of advice on confirmation and quantification of risk and on regulatory options  risk management  monitoring regulatory action  setting standards for procedures and methodologies to promote good vigilance practice  promotion of communication and exchange of information between the EMEA and national competent authorities  international cooperation

Slide 7 November 2008 Name Sarah Morgan © Crown copyright 2005 PhVWP Meets monthly (for ~ 3 days) in parallel with CHMP Agenda Drug Safety Issues Tour de table (emerging issues) ~6 per month* Issues at request of CHMP ~14 per month* Issues at request of NCAs ~9 per month* Guidelines (Volume 9A) Procedural/methodological issues (PSUR worksharing) *average from March-May 2008

Slide 8 November 2008 Name Sarah Morgan © Crown copyright 2005 Principles of EU pharmacovigilance  All MS run national pharmacovigilance systems (areas of expertise, levels of ADR reporting and resource vary)  Any safety concern identified within a MS should be shared with other MS  Worksharing – one MS will take the lead on assessment (rapporteur, RMS or appointed lead)  Work to achieve informal consensus for national products

Slide 9 November 2008 Name Sarah Morgan © Crown copyright 2005 PhVWP - challenges  Has to meet needs of multiple stakeholders – CHMP, CMD(h), member states  Heavy workload  Ensuring implementation of conclusions (decisions have no legal weight)

Slide 10 November 2008 Name Sarah Morgan © Crown copyright 2005 PhVWP recommendations

Slide 11 November 2008 Name Sarah Morgan © Crown copyright 2005 Communication to health professionals/patients  EMEA - centrally authorised products and issues under referral - website/press releases  Communication with health professionals and patients at national level  Direct Health Professional Communications from MAH – agreed at EU level  Different MS have different abilities to communicate at national level (e.g. bulletins)

Slide 12 November 2008 Name Sarah Morgan © Crown copyright 2005 Communications - national

Slide 13 November 2008 Name Sarah Morgan © Crown copyright 2005 EU system - challenges  Achieving consensus and timely action - key challenge for protection of public health and credibility of system  Ensuring effective work sharing and minimising duplication  Dealing with differences (clinical/political) between MS - impact on risk assessment, regulatory action and communication  Ensuring compliance (pharmacovigilance requirements, delivery of risk management plans)  Effective communication

Slide 14 November 2008 Name Sarah Morgan © Crown copyright 2005

Slide 15 November 2008 Name Sarah Morgan © Crown copyright 2005 EC Consultation on EU Pharmacovigilance System (2006)  Majority of response call for a change to the legal framework  Rationalisation needed (current system contradictory, complex, confusing, unclear)  Resources focussed on meeting administrative requirements – could be focussed on public health protection  Need clear roles and responsibilities and accountability  Increased and better use of resource  Better use of Eudravigilance and modern IT  Strengthen the system

Slide 16 November 2008 Name Sarah Morgan © Crown copyright 2005 Future challenges

Slide 17 November 2008 Name Sarah Morgan © Crown copyright 2005 EC initial proposals (published Dec 07)  Rationalise decision making (Pharmacovigilance Committee)  Clarify roles and responsibilities (Good Vigilance Practice)  Risk-based approach to PSURs  Simplified ADR reporting  Clear legal base for Risk Management Plans (penalties for non-fulfilment)  Transparency

Slide 18 November 2008 Name Sarah Morgan © Crown copyright 2005 PhVWP response.. “The Pharmacovigilance Working Party broadly welcomes the European Commission’s legislative proposals ….. The Working Party supports the strategic aims of the Commission, not only to address weaknesses in the current system, but to introduce a new approach where requirements are proportionate to risk, the current complexity and duplication is simplified, and best use is made of resources in the EU network.”

Slide 19 November 2008 Name Sarah Morgan © Crown copyright 2005 What next?  New legislation not before 2010  Future of PhVWP not certain, however: Important challenges - work needs to start now!

Slide 20 November 2008 Name Sarah Morgan © Crown copyright 2005 EudraVigilance – opportunity for signal detection Member States have access – need to incorporate into national procedures and co- ordinate at EU level..

Slide 21 November 2008 Name Sarah Morgan © Crown copyright 2005 Signal management  Explicit roles and responsibilities of Member States and industry in signal detection and analysis  Need for carefully co-ordinated work sharing  Use of best available tools

Slide 22 November 2008 Name Sarah Morgan © Crown copyright 2005 Advanced therapies  Long term follow up of efficacy and safety – recipients and donors  Need for registries  Risk management plans key

Slide 23 November 2008 Name Sarah Morgan © Crown copyright 2005 Changing global regulatory environment FDA Early Communication About an Ongoing Safety Review Omeprazole (Prilosec) Esomeprazole (Nexium) August 2007 … Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. …………… FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA has received and is reviewing new safety data about Prilosec (omeprazole) and Nexium (esomeprazole). …. The results from the study of Prilosec and analyses from an ongoing study of Nexium raised concerns that long-term use of Prilosec or Nexium may have increased the risk of heart attacks, heart failure, and heart-related sudden death in those patients taking either one of the drugs compared to patients who received surgery.

Slide 24 November 2008 Name Sarah Morgan © Crown copyright 2005 Transparency  Increasing public expectations  Global initiatives (FDA publication of signals)  Increasing demand for PhVWP papers (mainly from law firms and MAH)  Development of public PhVWP report to communicate agreed recommendations (including summary of assessment)  Patient representation on PhVWP

Slide 25 November 2008 Name Sarah Morgan © Crown copyright 2005 Conclusions  PhVWP central to pharmacovigilance network in EU  Complex system requires close integration and work- sharing  EC proposals for legislative change should bring many benefits  Need to continue to adapt to changing regulatory environment

Slide 26 November 2008 Name Sarah Morgan © Crown copyright 2005 Thank you for your attention. Any questions?