This blog covers the following key aspects:
- What is PSMF or PvMF?
A clear explanation of the Pharmacovigilance System Master File and its purpose. - Who is responsible for maintaining the PvMF?
An overview of the roles and responsibilities, particularly that of the QPPV. - Why is the PvMF important?
Understanding its regulatory significance and role in ensuring drug safety compliance. - Core components of the PSMF.
A detailed look at the structure, required contents, and annexes included in the PSMF.
Table of Contents
Introduction
The Pharmacovigilance System Master File (PSMF) is a comprehensive document that outlines how a pharmaceutical company manages its pharmacovigilance activities. It provides a detailed description of the pharmacovigilance system used by the Marketing Authorisation Holder (MAH) for one or more authorised medicinal products.
Each MAH must maintain at least one PSMF, and no more than one PSMF should exist per medicinal product.
Purpose
The Pharmacovigilance System Master File (PSMF) serves as a comprehensive and continually updated resource that provides the Qualified Person for Pharmacovigilance (QPPV) with oversight of the entire pharmacovigilance system. It ensures that both regulatory and company requirements are consistently met.
The PSMF also functions as:
- A planning and audit tool for internal evaluations of PV system components.
- A reference for regulatory authorities to understand how a company manages its pharmacovigilance obligations.
- A compliance tool to demonstrate how the Marketing Authorisation Holder (MAH) maintains oversight of PV activities.
The PSMF is mandatory for all authorised medicinal products, regardless of the authorisation procedure used. While it supports the QPPV in fulfilling legal oversight responsibilities, it is ultimately the MAH’s responsibility to ensure the accuracy and completeness of the PSMF at all times.
Importantly, the PSMF is intended as a system description, not a repository for operational results or detailed listings—such inclusions may fall outside its scope.
As a modular, living document, the PSMF evolves with the MAH’s pharmacovigilance system. It aids in:
- Supporting audits and inspections.
- Demonstrating system compliance.
- Identifying system gaps, risks, or failures.
According to GVP Module II, the PSMF must be made available to competent authorities within seven calendar days upon request, unless specified otherwise. Despite clear legislative guidance, inspection findings suggest that some elements are frequently misinterpreted or misapplied, underlining the need for clarity and diligence in maintaining the PSMF.
“A well-structured Pharmacovigilance System Master File is not just a regulatory requirement—it’s the backbone of patient safety and the foundation of trust in every medicinal product.”
Maintenance of the PSMF
The Pharmacovigilance System Master File (PSMF) must be continuously updated to reflect the current state of the pharmacovigilance system. It should be readily available for submission to National Competent Authorities (NCAs) at any time during the marketing authorisation process or post-authorisation.
Format and Layout Requirements:
- The PSMF must be prepared in English, unless a local language is specifically required by the relevant authority.
- It may be maintained in an electronic format, ensuring immediate availability upon request.
- Regardless of the format, the PSMF must be legible, complete, and structured in a way that ensures:
- Easy accessibility of all documents
- Traceability of all updates and historical changes
- Consistency with regulatory and internal requirements
Regulations Related to PSMF
The core regulatory guidance for the Pharmacovigilance System Master File (PSMF) is outlined in the following:
- GVP Module II:
Issued by the European Medicines Agency (EMA), this module serves as the primary guidance for the structure, content, maintenance, and use of the PSMF.
It outlines standards for the collection, handling, assessment, storage, and reporting of safety information across the pharmacovigilance system and ensures global regulatory alignment.
EU Legislation
The concept of the Pharmacovigilance System Master File (PSMF) was formally introduced in the 2010 revision of the Directive 2001/83/EC, through:
These legal instruments collectively govern pharmacovigilance obligations within the European Union.
Key Regulatory Requirements:
- The location of the PSMF must be registered in the extended EudraVigilance Medicinal Product Dictionary (xEVMPD).
- Any change in PSMF location must be reported immediately to the EMA.
- The PSMF location must also be made publicly accessible via the European Medicines web portal, as outlined in Regulation Article 26(1)(e), to support transparency and stakeholder communication.
Contents of the Pharmacovigilance System Master File (PSMF)
The PSMF provides a comprehensive overview of the pharmacovigilance (PV) system and includes the following components:
- Pharmacovigilance Personnel and Responsibilities
- Identification of individuals involved in PV activities and a description of their roles and responsibilities.
- Pharmacovigilance Organizational Structure
- Overview of the organizational setup, including:
- Marketing Authorization Holder (MAH)
- Contract Research Organization (CRO) (if applicable)
- Sources of Safety Data
- Description of all sources from which adverse event (AE) reports and other safety information are collected.
- Pharmacovigilance Processes
- Process Description: Narrative and flowchart illustrating the entire PV process, including data handling, documentation, and archival.
- Standard Operating Procedures (SOPs): A list and description of SOPs covering all critical PV activities.
- Computerized Systems and Databases: Details of IT systems, databases used, and associated security controls.
- Transfer of Responsibilities: Documentation of delegated or outsourced PV tasks.
- Quality Management System (QMS): Summary of how the QMS is integrated into PV activities, including quality assurance and control measures.
- PV System Performance Monitoring
- Evidence and metrics demonstrating continuous monitoring, evaluation, and compliance of the PV system.
- Qualified Person Responsible for Pharmacovigilance (QPPV)
Summary of the PSMF
The summary section provides essential high-level information, including:
- PSMF Reference Number (e.g., PSMF-XXXXXX)
- PSMF Physical/Hosting Location
- QPPV Details
- Name, contact information, and operational location of the QPPV.
- Signed Statement
- A declaration from both the MAH and the QPPV confirming that the QPPV has the authority, resources, and systems necessary to fulfill regulatory obligations in accordance with Regulation (EU) 2019/6 (Article 22(2)(b)(i)).
- Record Management System
- Description of the system used for managing adverse event reports, including the name of the database (if applicable).
- Logbook
- A record of all updates, modifications, and changes made to the PSMF, including dates and responsible personnel for each change.
PSMF Reference Number
Regulatory Basis: Regulation (EU) 2019/6, Article 77(8)
The Qualified Person Responsible for Pharmacovigilance (QPPV) is responsible for the creation, maintenance, and management of the Pharmacovigilance System Master File (PSMF), including the following tasks:
- Preparation and Maintenance
- Ensuring the PSMF is accurate, up-to-date, and compliant with regulatory requirements.
- Assignment and Communication of Reference Number
- A unique PSMF reference number must be assigned and communicated to the pharmacovigilance database for each associated product.
- Format: A free-text format such as PSMFXXXXXXX may be used.
The reference number must be: - Unique to the Marketing Authorization Holder (MAH)
- Specific to the group of products it covers
- Uniqueness at EU Level
- The combination of the PSMF reference number, PSMF location, and MAH organization is expected to be unique across the EU.
- Notification of PSMF Location
- The QPPV must notify the relevant National Competent Authorities (NCAs) and the European Medicines Agency (EMA), as applicable, regarding the physical or electronic location of the PSMF.
Location of the Pharmacovigilance System Master File (PSMF)
The location of the PSMF must be clearly defined and compliant with regulatory expectations. The following principles apply:
- The Qualified Person Responsible for Pharmacovigilance (QPPV) must have immediate and unrestricted access to the PSMF at all times.
- The PSMF may be maintained electronically, provided it remains readily accessible and is stored on a secure server, regardless of its physical location.
- As per regulatory guidance, the PSMF must be physically located at one of the following:
- The site where the main pharmacovigilance activities of the Marketing Authorisation Holder (MAH) are conducted,
or - The location where the QPPV operates.
- The site where the main pharmacovigilance activities of the Marketing Authorisation Holder (MAH) are conducted,
The designated location must be recorded in the eXtended EudraVigilance Medicinal Product Dictionary (xEVMPD), and any changes to the location must be promptly communicated to the European Medicines Agency (EMA).
Sections of the Pharmacovigilance System Master File (PSMF)
The PSMF comprises a structured main body divided into clearly defined sections as outlined in GVP Module II, along with corresponding annexes. The data presented in the PSMF may originate from multiple internal systems and departments within the Marketing Authorisation Holder’s (MAH) organization—for example, CAPA records may be drawn from a quality system, while compliance metrics may be sourced from safety databases.
Note: The PSMF’s location and contact details may be made publicly accessible via the EMA web-portal to support transparency and communication.
| Section A | Information on the PSMF (PSMF reference number, PSMF location) | Annex 1 – logbook |
|---|---|---|
| Section B | QPPV, Assisting veterinary surgeon, and back up procedures | Annex 2 – QPPV additional info., e.g. CV, proof of registration with pharmacovigilance database |
| Section C | Marketing Authorisation holder information | Annex 3 – e.g., list of products, list of regional representatives, list of PhV sites, etc. |
| Section D | Document management system (including record management system for adverse event recording) | |
| Section E | Quality management system for pharmacovigilance activities | Annex 4 – list of procedures, list of scheduled and completed audits, etc. |
| Section F | Contractual arrangements between MAH and third parties concerning pharmacovigilance activities | Annex 5 – lists of tasks delegated (MAH/QPPV), list of contracts/agreements |
Maintenance of the Pharmacovigilance System Master File (PSMF)
The PSMF must accurately reflect the pharmacovigilance system in place. Given the dynamic nature of pharmacovigilance activities, there is no expectation to include exhaustive, real-time listings or document inventories. These may change frequently, and as such, the Qualified Person for Pharmacovigilance (QPPV) cannot be expected to certify their absolute accuracy at any given moment.
However, annexes to the PSMF are expected to be continuously updated, as they form the foundation of pharmacovigilance documentation. The PSMF serves as a critical reference document for drug safety operations and requires informed, expert management to ensure compliance with all regulatory expectations.
A valid and up-to-date PSMF must be in place at the time of submission of any new marketing authorization application. Both the European Medicines Agency (EMA) and national competent authorities may request access to the PSMF at any point during the marketing authorization process or post-authorization lifecycle. Upon such request, the PSMF must be provided within 7 calendar days.
To maintain integrity and control, access to the PSMF should be restricted to authorized personnel only. This ensures proper governance over its content, with clearly assigned responsibilities for change control, updates, and archiving.
Audit Information in the PSMF
The PSMF must include essential details regarding internal pharmacovigilance audits. Specifically, it should describe the audit planning strategy, ensuring that all critical components of the pharmacovigilance system are audited at least once every five years.
For each significant audit finding, a brief summary must be included, along with associated Corrective and Preventive Action (CAPA) details—such as the date the issue was identified, the proposed corrective actions, and the expected date of resolution. CAPAs must remain documented within the PSMF until they are formally closed and verified.
As this audit information forms part of the main body of the PSMF, it is also reflected in the PSMF logbook, which must be diligently maintained. Keeping this section current can be challenging but is vital for demonstrating ongoing compliance.
QPPV and Company Sign-Off
Each time the PSMF is updated, it must be formally reviewed and signed off by:
- The Qualified Person for Pharmacovigilance (QPPV), confirming awareness of the most recent changes.
- The Head of Drug Safety (or equivalent responsible person within the Marketing Authorization Holder), affirming that the contents of the PSMF are accurate and up-to-date.
This sign-off may be documented either through traditional paper-based methods or, preferably, by secure electronic means, ensuring traceability and regulatory compliance.
Logbook
he logbook in the context of a Pharmacovigilance System Master File (PSMF) is a controlled record that tracks changes, updates, and version history made to the PSMF and its annexes.
It ensures transparency, traceability, and regulatory compliance, as required by EU GVP Module II and similar international guidelines.
Annexes in the PSMF
The PSMF should include annexes containing detailed, supporting documentation essential for regulatory compliance and operational clarity. These typically include:
- List of pharmaceutical products, detailing the product name, active substance(s), and excipients.
- List of contractual agreements covering all delegated pharmacovigilance (PV) activities, including the relevant products.
- List of PV tasks delegated by the Person Responsible for Pharmacovigilance (PVOIC).
- Audit and inspection records, including:
- A list of completed internal and external (regulatory) audits/inspections.
- A forward-looking schedule of planned audits and inspections.
Key Takeaways
The PSMF is a legal requirement for all Marketing Authorisation Holders (MAHs), aimed at harmonising and strengthening pharmacovigilance practices.
While the intention is to maintain one PSMF per company, multiple PSMFs may be appropriate when managing significantly different product categories (e.g., pharmaceuticals and vaccines).
The PSMF is maintained by the MAH/QPPV and is not part of the marketing authorisation dossier.
The PSMF can be maintained electronically and must be searchable and printable upon request.
Physical copies are not mandatory, but access must be ensured for Competent Authorities.
The QPPV plays a critical role in updating and overseeing the accuracy of the PSMF.
The PSMF is a key focus area during regulatory inspections and should be kept inspection-ready at all times.
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Conclusion
This article offers a concise yet comprehensive overview of the Pharmacovigilance System Master File (PSMF)—a vital document in the effective operation of a pharmacovigilance system.
Understanding the structure, components, and regulatory requirements of the PSMF enables better preparation and compliance for both new and existing marketing authorisation holders. It serves as a cornerstone of PV oversight, contributing significantly to public health and safety.
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Stay informed. Stay compliant.
References:
- Guideline on good pharmacovigilance practices (GVP) – Module II – Pharmacovigilance system master file (Rev 2), n.d.
- https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-documents/PSUR_PV_AEFI/Guidance_Documentpsur2.pdf
- Comparison of EU-Pharmacovigilance System Master File, n.d.
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