1. GIQAR Annual Congress 25 – 26 th May 2006 1 Pv QA: Quality Assurance for Pharmacovigilance Allison Jack Manager, R&D Oversight – GCP/PV, Pfizer Ltd BARQA Chair Good Pharmacovigilance Practice Committee & BARQA Board Member

2. GIQAR Annual Congress 25 – 26 th May 2006 2 AGENDA Part 1: –PV QA a new discipline –Differences between GCP QA and PV QA –Audit plan for PV audit Part 2: –BARQA PV activities

3. GIQAR Annual Congress 25 – 26 th May 2006 3 PV QA: A New Discipline

4. GIQAR Annual Congress 25 – 26 th May 2006 4 PV QA: A New Discipline Why audit Evolving regulatory requirements –Risk management plan for submissions –QP responsibilities Specific regulatory inspection programmes Key system concerned with subject safety

5. GIQAR Annual Congress 25 – 26 th May 2006 5 Differences between GCP and PVQA

6. GIQAR Annual Congress 25 – 26 th May 2006 6 Differences between GCP and PV QA There are more regulations: –The pre-marketing clinical regulations familiar to GCP e.g. ICH GCP & EU Directive –The post-marketing regulations relating to Marketing authorisation holder responsibilities, PvQP responsibilities etc. e.g. volume 9 There are more people that you interact with during the audits –The familiar individuals e.g. CRA, Project Manager, Regulatory personnel. –Then those rarely spoken to, such as: Sales and marketing personnel, Sales Reps, product managers Medical Information personnel Drug safety personnel Call centre personnel Product quality/complaints personnel Security, receptionists

7. GIQAR Annual Congress 25 – 26 th May 2006 7 Differences between GCP and PV QA There are more documents/activities that you need to understand in detail: –The clinical documents you are already familiar e.g. Protocols, CRFS, Investigator Brochures, statistical reports, final study reports,sponsor files –Those that are rarely touched on in clinical audits such as: Periodic safety update Reports (PSURs), Product Labelling, Marketing Partner contracts, Post marketing documents relating to Patient Assistance Programs, Named patient supplies, surveys, registries, market research, outcomes research You get to see your company at a level few others ever see it: –You see the entire organisation and how things fit together (or don’t!) –You get to see how complicated it can get when marketing partners are invloved

8. GIQAR Annual Congress 25 – 26 th May 2006 8 There are number of different adverse events sources: –In GCP sources are only from clinical trials via investigators –In post-marketing additional sources of AE cases include: Literature cases Spontaneous cases from Health Care Professionals or consumers Solicited reports from marketing programs such as disease management programs, patient compliance programs, market research, as well as non-interventional studies or post-authorisation safety studies (PASS) Differences between GCP and PV QA

9. GIQAR Annual Congress 25 – 26 th May 2006 9 The myth about PV auditing “You’re just looking at SAEs and SUSARs, how hard can it be?”

10. GIQAR Annual Congress 25 – 26 th May 2006 10 The reality about PV auditing SAEs and SUSARs are a very small part of PV audits The majority of safety information is collected during post marketing activities e.g. spontaneous/solicited

11. GIQAR Annual Congress 25 – 26 th May 2006 11 Pharmacovigilance Audit Plan

12. GIQAR Annual Congress 25 – 26 th May 2006 12 PV Audit Plan Audit Approach: –Systems Approach –Evaluation of whole process, for example from source in marketing company to company global database in headquarters –This includes looking at the interfaces with global safety organisation, local health authorities –Gaps in system, is it an IT issue? –Facility Focus – looking at the local marketing company –Compliance with sponsor procedures, regulatory requirements

13. GIQAR Annual Congress 25 – 26 th May 2006 13 Adverse Event Reporting CROs Signal Detection Marketing/Licensing Partners Regulatory Requirements Qualified Person Marketing Companies Clinical Trials Medical Information

14. GIQAR Annual Congress 25 – 26 th May 2006 14 Audit Plan for Global Safety Processes Areas of focus: –Individual cases process handling –Expedited reporting –Signal detection/risk management activities –Computerised systems –European Union Qualified Person *These topics are sufficiently complex to warrant an individual focused audit

15. GIQAR Annual Congress 25 – 26 th May 2006 15 Audit Plan for Marketing Company Areas of focus: –Quality Operations –Safety Training –Medical Information –Regulatory –Safety database –Adverse Event Processing – Clinical – Archives – Product Complaint – Marketing – Interfaces with Safety – Sales Representative

16. GIQAR Annual Congress 25 – 26 th May 2006 16 Audit Conduct Quality Operations –QA/QC programs/initiatives –Quality plans –Review of documentation associated with quality activities e.g. planning documentation

17. GIQAR Annual Congress 25 – 26 th May 2006 17 Audit Conduct Safety Training –Roles and responsibilities –Who is required/expected to receive safety training –Review training materials –Review training records Management of Safety SOPs Safety agreements (in the cases of co-licensing) Call centres (site visit if needed)

18. GIQAR Annual Congress 25 – 26 th May 2006 18 Audit Conduct Adverse Event Processing –Walk-through case processing –Roles and responsibilities of safety physicians –Processes relating to safety reporting –Safety database –Local process for AEs (including spontaneous and clinical) and follow-up reports –Archiving of safety documentation –Review of interactions with product quality and safety –Review of processing of CT SAEs –Review of PSUR production

19. GIQAR Annual Congress 25 – 26 th May 2006 19 Audit Conduct Medical Information –Review process for handling, tracking and answering inquiries –Assess local literature review process –Reconciliation process between Medical Information and safety AEs –Complaint handling –Database

20. GIQAR Annual Congress 25 – 26 th May 2006 20 Audit Conduct Regulatory –Regulatory authority query process –PSUR Submissions to regulators –Interactions with safety group Marketing –Review on-going patient contact programs –Interview a sales representative –Websites (potential source of adverse events)

21. GIQAR Annual Congress 25 – 26 th May 2006 21 Audit Conduct Marketing Partners/Contractors –Discuss interactions with partners –Responsibility for PV reporting –Review CRO training program –Study and CRO monitoring review process –Review example contracts/agreements Clinical –Review Dear Doctor letters process –IB process

22. GIQAR Annual Congress 25 – 26 th May 2006 22 Audit Conduct Archives –Review on-site/off-site facility Product Complaint –Interaction with Pharmacovigilance

23. GIQAR Annual Congress 25 – 26 th May 2006 23 BARQA PV Activities

24. GIQAR Annual Congress 25 – 26 th May 2006 24 Good Pharmacovigilance Practice Working Party (1) Set up to explore and provide support in GPvP to BARQA members Final outputs –The Regulatory Framework for Pharmacovigilance (published January 2006 as an article in QUASAR) –Practical Guidance for Pharmacovigilance Audits* –Practical Guidance for Pharmacovigilance Inspections* Links with other groups e.g. AIOPI, EFGCP *To be published in May 2006

25. GIQAR Annual Congress 25 – 26 th May 2006 25 Good Pharmacovigilance Practice Working Party (2) Good Pharmacovigilance Practice Discussion Forum was held in June 2005 –Risk management considerations applied during clinical development –QP role, need for Pharmacovigilance and the MAH responsibilities –Development of a risk management plan –Auditing Pharmacovigilance systems

26. GIQAR Annual Congress 25 – 26 th May 2006 26 Good Pharmacovigilance Practice Committee (1) Inaugurated in March this year –Set up in response to membership needs and recommendation of the working party Members includes: –PV auditors and audit group managers –PV practitioners including QPs –UK, France and Russia –PV regulatory affairs and regulatory intelligence experts –National Health Service auditor –Veterinary Pharmacovigilance

27. GIQAR Annual Congress 25 – 26 th May 2006 27 Good Pharmacovigilance Practice Committee (2) Scope –To span human and veterinary medicinal products in research and licensed products Objectives –To serve the needs of the membership in the emerging field of Pharmacovigilance regulation and inspection –Establish links and develop understanding with US, Japan and other territories to foster understanding of global Pharmacovigilance requirements and expectation

28. GIQAR Annual Congress 25 – 26 th May 2006 28 Good Pharmacovigilance Practice Committee (3) Next Steps: –PV auditing course –BARQA Annual Conference PV stream - 6 presentations PV committee stand –BARQA website PV section

29. GIQAR Annual Congress 25 – 26 th May 2006 29 Good Pharmacovigilance Practice Course Topics include regulatory framework, role and responsibilities of MAH, case processing, PV quality system and inspections Course is for PV QPs, auditors, regulatory affairs professionals, medical assessors, marketing managers Course was initiated in September 2005 The course is run twice a year

30. GIQAR Annual Congress 25 – 26 th May 2006 30