An Introduction to the Pharmacovigilance System Master File

AGENDA

• Overview - Guidelines on Good Pharmacovigilance Practices (GVP)
• Overview - Module II - Pharmacovigilance System Master File (PSMF)
• Moving Forward

GUIDELINES ON GOOD PHARMACOVIGILANCE PRACTICES (GVP)

Regulation 1235/2013 Directive 2010/84EC:

• Published December 2010
• Implantation July 2012
• Legally enforceable legislation

Implementing Regulation 520/2012

• Published June 2012
• Legally enforceable legislation

Good Pharmacovigilance Practices (GVP)

• Consultation & Publication 2012 & 2013
• Detailed operation guidance (day to day)
• Not legally enforceable

Transitional Provisions: Implementation 2012 - 2016

IMPACT

• European Economic Area (EEA)
  • European Union (28 Countries)
  • European Free Trade Association (3 Countries)
• Marketing Authorisation (Pending or Approved)
• Phase IV Studies

Good Pharmacovigilance Practices (GVP)

• EEA GVP Modules
• I Pharmacovigilance Systems and their Quality Systems Published 22-Jun-2012
• II Pharmacovigilance System Master File Published 22-Jun-2012 Update 09-Apr-2013
• III Pharmacovigilance Inspections Published 12-Dec-2012
• IV Pharmacovigilance Audits Published 12-Dec-2012
• V Risk Managements Systems Published 22-Jun-2012
• VI Management & Reporting of Adverse Reactions to Medicinal Products Published 22-Jun2012
• VII Periodic Safety Update Report Published 22-Jun-2013 Consultation Rev 1 19-Apr-2013
• VIII Post-Authorisation Safety Studies Published 22-Jun-2013 Update 19-Apr-2013
• IX Signal Management Published 22-Jun-2013
• X Additional Monitoring Published 19-Apr-2013
• XI Public Participation in Pharmacovigilance Consultation Q3 2013
• XII Continuous Pharmacovigilance, Ongoing Benefit-Risk Evaluation, Regulatory Action and Planning of Public Communication Consultation Q3 2013
• XIII Void XIV International Coorperation Consultation Q3 2013
• XV Safety Communication Published 22-Jan-2013
• XVI Risk-Minimisation Measures: Selection of Tools & Effectiveness Indicators Consultation Q2 2013

Describe the Pharmacovigilance System

Support/Document Compliance

PHARMACOVIGILANCE SYSTEM OVERVIEW

• Module 1.8.1 Marketing Authorisation Application Dossier
  • Proof of EEA QPPV Services
  • Country in which EEA QPPV resides & operates
  • Contact details for EEA QPPV (24 hour)
  • Statement signed by applicant that the applicant has the necessary means to fulfill the tasks and responsibilities listed in Title IX (9)
  • Reference Confidential property of Optum. Do not distribute or reproduce without express permission from Optum. 16 to the location of the PSMF

PSMF LOCATION

• Within the EEA
  • Site where main Pharmacovigilance activities are performed OR
  • Where the EEA QPPV operates
    • Physical office address where the data can be directly accessed
    • Location must be entered into the eXtended EudraVigilance Medicinal
    • Product Dictionary (xEVMPD)
    • Change in location must be immediately notified to EMA
    • Location will indicate supervisory agency (centrally authorised products only)

EEA QUALIFIED PERSON FOR PV SECTION

• Description of responsibilities guaranteeing

• EEA QPPV has sufficient authority

• Summary CV

• Contact Details

• Details of Back-Up Arrangements

• National QPPV information

PSMF – ORGANISATIONAL STRUCTURE SECTION

• Organisational structure of MAH
• Sites where Pharmacovigilance activities take place
• Description of delegated Pharmacovigilance activities

PSMF – SOURCES OF SAFETY DATA

• Who, What, How & When
• Spontaneous
• List of solicited programmes
• Patient Support Programmes, Reimbursement Programmes, Marketing Surveys, etc.
• Studies
• Literature
• Agencies
• Contract Partners

• Flow Diagram / Description of Process

PSMF – DATABASES

• Location, functionality, operational responsibility for computerized systems and databases used to receive, collate, record and report safety information
• Assessment of their fitness for purpose
• Validation status
• Change control, nature of testing, back-up procedures, and electronic data repositories, nature of documentation available

PSMF – PHARMACOVIGILANCE PROCESSES SECTION

• Description of Procedural Documentation
  • SOPs/Manuals, etc
  • Nature of data held
  • Indication of how records held
• Description of Process, Data Handling and Records
  • Continuous monitoring of risk-benefit profile
  • Risk management systems, including effectiveness of risk minimisation
  • Safety data processing
  • PSUR scheduling, production & submission
  • Communication of safety concerns to agencies, healthcare professionals and patients
  • Implementation of safety variations to product information

PSMF – PHARMACOVIGILANCE SYSTEM PERFORMANCE

• How timeliness of expedited submissions is monitored
• Description of metrics for monitoring quality of submissions, including information provided by agencies
• How timeliness of periodic submissions is monitored
• How timeliness of safety variation submissions is monitored
• How adherence to agency commitments is monitored

PSMF – QUALITY SYSTEM

• Document & record control / Archiving
• Management of procedural documents
  • Note of open SOP deviations
• Training procedures
• Auditing
  • Note of open CAPA for critical & major audit findings

PSMF - ANNEXES

• List of medicines products, authorisation & marketing status, safety monitoring requirements
• List of Ongoing Studies
• List of written policies & procedures
• List of contractual agreements
• List of tasks delegated by EEA QPPV
• List of all audits completed in last 5 years
• Audit schedule
• List of performance indicators

CHANGE CONTROL

• Main PSMF Sections
  • Formal change control process & version control
• PSMF Annexes
  • History of changes
  • Maintain inside or outside of PSMF structure
  • If maintained outside of PSMF, keep history of when generated for PSMF purposes

THE SECRETS TO SUCCESS

• Planning, planning, planning
• Identification of resources
  • People
    • Cross-functional expertise
• Technology
  • Network folder?
  • SharePoint?
  • In-house Documentation Management System?
  • Off-the-shelf IT solution?
  • Custom-built solution?
• Implementation Project Management
• Access rights
  • Who?
  • Prevention of inappropriate distribution
• Maintenance
  • Who? PSMF Administrator?
  • How frequently? Main Documents Versus Annexes?