Pharmacovigilance System Master File (PSMF)

The Pharmacovigilance System Master File (PSMF) is a document, designed to summarize the pharmacovigilance (PV) system of the marketing authorization holder (MAH). This document is named differently in many countries, namely, PvMF in India and in the EU, it is known as PSMF. 

Objective of PSMF:

• Describe the pharmacovigilance (PV) system
• Support/document PV system’s compliance with the requirements
• Provides:
  • information on
    • aspects of compliance in relation to the system
    • deficiencies in the system, non-compliance with the requirements
    • risks or actual failure in the conduct of specific PV aspects and
    • the action/measure taken
• Contribute to:
  • the fulfilment of supervisory responsibilities of the qualified personnel for PV activities (QPPV),
  • planning and conduct of internal audits and
  • external inspections/verification of compliance by the national competent authorities (NCAs)
  • appropriate management of and improvement(s) to the pharmacovigilance system.
• Thereby, assuring PV system implementation and compliance.

Why do companies need PSMF? 

The legal requirement for MAHs, to maintain and make the PSMF available upon request, is to strengthen and rationalize the monitoring of the safety of medicinal products, and for PV activities harmonization. The content of any PSMF should clearly display global availability of the safety information for medicinal products authorized in the region.

PSMF requirements in other countries:

• Recently estimated figures suggested that over 30 countries across the globe, now have requirements for a PSMF. 
• Countries governed by the League of Arab States accept the EU-PSMF, but require additional document names, such as the PV System Sub-File. 
• Meanwhile, India requires MAH to maintain a PSMF, where the main PV activities take place. 
• TGA Australia accepts a global PSMF with a description of the Australian PV system, whereas other ICH regions, namely, Japan PMDA, as well as Health Canada or USFDA do not mandate a PSMF. However, all the Health Authorities can request for an EU PSMF, if the MAH has products registered in the EU.

How should PSMF be maintained? 

• In the EU, the PSMF needs to be located, either at the site where the main PV activities are performed, or at the site where the Qualified Person for PV (QPPV) operates from. 
• Following EEA agreements, the PSMF can also be located in Norway, Iceland, or Liechtenstein. 
• The required location information for the PSMF is a physical office address of the MAH, or a contracted third party. 
• This document should be written in English, unless the MAH holds approvals in only one Member State, wherein, it can be written in the EU official language for that territory. Post Brexit transition, effective January 1, 2021, MAHs need to ensure that the UK PSMF is located at the same point in the UK, from where the reports of suspected adverse reactions are referred to. 
• The PSMF could be stored either in paper or in electronic form. It could be a virtual document, existing on different servers in the company, or at suppliers of data services, but a clearly arranged printed copy needs to be made available for inspections.

How many PSMF?

• One MAH + One PV system = OnePSMF
  • One PSMF describes PV system for one or more medicinal products of one MAH
• One MAH + Multiple PV system = MultiplePSMF
  • MAH may apply separate PV systems for different categories of products (vaccines, consumer health)
  • Describe each system in a separate PSMF
• Multiple MAH = MultiplePSMF
  • PV system may be shared by several MAH
    • each MAH responsible for a PSMF to describe PV system applicable for its product
  • MAH may delegate PV activity to contractor
    • PSMF of MAH may cross refer to all or part of the PSMF managed by the contractor’s system
    • MAH retains ultimate responsibility for the PV system
  • Written agreement are mandatory.

Contents of PSMF

• Indexed with appropriate sections for efficient navigation
• Partitioned
  • Sections:
    • QPPV
    • MAH’s organisational structure
    • Safety data sources
    • Computerised systems and databases
    • PV processes
    • PV system performance and
    • Quality system
  • Annexes

In the annexes, the below-mentioned items need to be detailed in a comprehensive way: 

• The CV of the QPPV 

List of: 

• Contracts and agreements including subcontractors with copies of the signed agreements 
• Sources of safety data including affiliates and third parties 
• Computerized systems and databases 
• SOPs and procedures 
• Performance indicators 
• Scheduled and completed audits and those with significant findings and unresolved issues 
• Products and EU countries wherever approved 
• Audit trail of changes to the PSMF over the last five years

References:

• hps://ec.europa.eu/health/sites/health/files/files/eudralex/vol1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdf 
• https://www.ema.europa.eu/en/documents/presentation/presentation-pharmacovigilance-system-master-file-approach-towards-system-simplification_en.pdf
• hps://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:348:0074:0099:EN:PDF 
• hps://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:348:0001:0016:EN:PDF
• hps://www.gov.uk/guidance/guidance-on-qualified-person-responsible-for-pharmacovigilance-qppv-including-pharmacovigilance-system -master-files-psmf-if-the-uk-leaves-the-eu-w 
• http://www.panaceapharmaprojects.com/panaceainsights/global-pharmacovigilance-what-are-the-challenges/
• https://pink.pharmaintelligence.informa.com/PS122184/India-Specifies-Requirements-For-Pharmacovigilance-System-Master-File-Qualified-Person
• https://www.tga.gov.au/sites/default/files/pharmacovigilance-inspection-program-guidance-medicine-sponsors.pdf