GIQAR Annual Congress 25 – 26th May 2006 1

Pv QA: Quality Assurance for Pharmacovigilance

Allison JackManager, R&D Oversight – GCP/PV, Pfizer LtdBARQA Chair Good Pharmacovigilance Practice

Committee & BARQA Board Member

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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

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PV QA: A New Discipline

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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

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Differences between GCP and PVQA

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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

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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

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• 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

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The myth about PV auditing

“You’re just looking at SAEs and SUSARs, how hard can it be?”

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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

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Pharmacovigilance Audit Plan

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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

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Adverse Event

Reporting

CROs

Signal Detection

Marketing/Licensing Partners

Regulatory Requirements

Qualified Person

Marketing Companies

Clinical Trials

Medical Information

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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

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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

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Audit Conduct

• Quality Operations– QA/QC programs/initiatives– Quality plans– Review of documentation associated with

quality activities e.g. planning documentation

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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)

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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

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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

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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)

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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

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Audit Conduct

• Archives– Review on-site/off-site facility

• Product Complaint– Interaction with Pharmacovigilance

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BARQA PV Activities

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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

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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

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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

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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

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Good Pharmacovigilance Practice Committee (3)

• Next Steps:– PV auditing course– BARQA Annual Conference

• PV stream - 6 presentations

• PV committee stand

– BARQA website PV section

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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

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