Introduction

The Pharmacovigilance System Master File (PSMF) serves as a cornerstone document within pharmacovigilance systems, providing a detailed overview of a company’s PV activities and organizational structures.

While the European Union (EU) pioneered the implementation of the PSMF under the Good Pharmacovigilance Practices (GVP) Module II, other regions, including the Kingdom of Saudi Arabia (KSA), have followed suit with localized adaptations.

European Union (EU): Role of PSMF

The PSMF is a legal requirement in the EU. This guidance concerns the requirements for the PSMF and is applicable for any medicinal product authorised in the EU, irrespective of the marketing authorisation procedure.

The required content and management of the PSMF apply irrespective of the organisational structure of a marketing authorisation holder, including any subcontracting or delegation of activities, or their location. Irrespective of the location of other activities, the qualified person for pharmacovigilance (QPPVs) residence, the location at which he/she carries out his/her tasks and the PSMF location must be within the EU.

The PSMF shall describe the pharmacovigilance system and support/document its compliance with the requirements. As well as fulfilling the requirements for a PSMF laid down in the legislation and guidance, it shall also contribute to the appropriate planning and conduct of audits by the applicant or marketing authorisations holder(s), the fulfillment of supervisory responsibilities of the QPPV, and of inspections or other verification of compliance by national competent authorities. The PSMF provides an overview of the pharmacovigilance system, which may be requested and assessed by national competent authorities during marketing authorisation application(s) or post-authorisation.

Through the production and maintenance of the PSMF, the marketing authorisation holder and the QPPV should be able to:

• gain assurance that a pharmacovigilance system has been implemented in accordance with the requirements.
• confirm aspects of compliance in relation to the system.
• obtain information about deficiencies in the system, or non-compliance with the requirements.
• obtain information about risks or actual failure in the conduct of specific aspects of pharmacovigilance.

Why It Matters

• Facilitates regulatory inspections
• Centralizes all PV system components
• Provides clarity on roles, processes, and compliance status
• Demonstrates ongoing system performance and quality assurance

European Union (EU): A Mature and Structured Approach

Regulatory Framework

The EU introduced the PSMF requirement as part of Directive 2010/84/EU and Regulation (EU) No. 1235/2010. GVP Module II provides detailed guidance on content, format, maintenance, and location of the PSMF.

Key Requirements

• Location: The PSMF shall be located within the EU, either at the site where the main pharmacovigilance activities are performed or at the site where the qualified person responsible for pharmacovigilance operates [IR Art 7(1)], irrespective of the format (paper-based or electronic format file).

 Following European Economic Area (EEA) agreements, the PSMF may also be located in Norway, Iceland or Liechtenstein

• QPPV Oversight: The EU QPPV is responsible for maintaining the PSMF and ensuring its accuracy.
• Structure:

The PSMF can be broken into 3 sections. The cover page, the main body (core) and the annexes.

1. The cover page contains a brief overview of the details of the MAH, the QPPV, and information on any other Pharmacovigilance systems the MAH is involved in.
2. The PSMF’s main body contains the primary information describing the MAH’s Pharmacovigilance system.
3. The annexes include supplementary information to add more detail, or specific data on system compliance, to the content provided in the main body.

The PSMF’s main body is separated into 7 distinct modules:

1. QPPV
2. Organisational Structure of the MAH
3. Sources of Safety Data
4. Computerised Systems and Databases
5. PV Processes
6. PV System Performance
7. Quality System

Each Module covers a critical part of the MAH’s Pharmacovigilance system.

There are then 9 annexes that roughly mirror the main body modules, with the exceptions of annexes H and I:

1. The QPPV
2. Organisational Structure
3. Sources of Safety Data
4. Computerised Systems & Databases
5. PV Processes
6. PV System Performance
7. Quality System
8. List of Marketing Authorisations
9. Document and Record Control

• Submission: At the time of marketing authorisation application, the applicant should submit electronically the PSMF location information using the agreed format [IR Art26 1(a)], and subsequently include in the application, the PSMF reference number, which is the unique code assigned by the EudraVigilance (EV) system to the master file when the EudraVigilance Medicinal Product Report Message (XEVPRM) is processed .
• Further to the granting of a marketing authorisation, the PSMF will be linked by the marketing authorisation holder to the EVMPD product code. All PSMFs must be registered in the Article 57 database
• Each EU PSMF must have a unique code assigned by the EMA’s Eudravigilance system. The code is assigned when the PSMF is registered in the Article 57 database (xEVMPD). The PSMF code is tied to the location of the PSMF and any change to the PSMF’s location information must be updated in the xEVMPD within 30 calendar days of the change.

Updates to the PSMF

• There is no fixed rule for how often the PSMF should be updated; the frequency should reflect the complexity of the pharmacovigilance system it describes.
• More complex systems (e.g., multiple products, frequent changes) require more frequent updates than simpler systems.
• If requested by a competent authority, the MAH must provide an up-to-date PSMF within 7 calendar days, unless otherwise specified.
• Annexes, which contain detailed information, typically need more frequent updates than the main body.
• The QPPV is responsible for ensuring updates are made, including maintaining a logbook in Annex I to track all changes.
• All updates should be subject to a quality review and QPPV approval before finalisation.

Saudi Arabia (KSA): A Rapidly Evolving Regulatory Landscape

The PSMF is a legal requirement in the KSA. This guidance concerns the requirements for the PSMF and is applicable for any medicinal product authorized in the KSA, irrespective of the marketing authorization procedure.

The required content and management of the PSMF apply irrespective of the organizational structure of a MAH, including any subcontracting or delegation of activities, or their location. Irrespective of the location of other activities, the QPPV’s residence, the location at which he/she performs his/her tasks and the PSMF location must be within the KSA.

The content of the PSMF should reflect global availability of safety information for medicinal products authorized in the KSA, presenting information on the pharmacovigilance system applied at global, regional and local levels.

SFDA Requirements

• Registration:

The MAH should include a summary of the pharmacovigilance system in the authorization application. The summary should include the following elements in module 1.6.1 of the dossier:

• QPPVs must be free fulltime for Pharmacovigilance activities and the local QPPV must be registered at SFDA QPPV website registration form.
• Official Contact details of the qualified person such as official email having name or QPPV and Deputy
• Statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in this GVP module.
• Reference to the location where the pharmacovigilance system master file for the medicinal product is kept

Location:

The PSMF shall be located within the KSA, either at the site where the main pharmacovigilance activities are performed or at the site where the QPPV operates, irrespective of the format (paper-based or electronic format file) and the local QPPV must have access to the PSMF file (having a copy of it) and the local QPPV is the owner for the local PSSF. If the PSMF in electronic format, the address will be mentioned clearly that it is virtual document located in such sharing point or site, can be accessed by such personnel (specify the positions that are authorized to have an access).

Any change to the location shall be notified immediately to the SFDA. The required location information for the PSMF is a physical office address of the MAH or a contracted third party. Where the PSMF is held in electronic form, the location stated must be a site where the data stored can be directly accessed, and this is sufficient in terms of a practical electronic location.

• Structure:

The PSMF can be broken into 3 sections. The cover page, the main body (core) and the annexes.

• The cover page contains a brief overview of the details of the MAH, the QPPV, and information on any other Pharmacovigilance systems the MAH is involved in.
• The PSMF’s main bodycontains the primary information describing the MAH’s Pharmacovigilance system.
• The annexesinclude supplementary information to add more detail, or specific data on system compliance, to the content provided in the main body.

The PSMF’s main body is separated into 7 distinct modules:

QPPV

Organisational Structure of the MAH

Sources of Safety Data

Computerised Systems and Databases

PV Processes

PV System Performance

Quality System

Each Module covers a critical part of the MAH’s Pharmacovigilance system.

There are then 9 annexes that roughly mirror the main body modules, with the exceptions of annexes H and I:

1. The QPPV
2. Organisational Structure
3. Sources of Safety Data
4. Computerised Systems & Databases
5. PV Processes
6. PV System Performance
7. Quality System
8. List of Marketing Authorisations
9. Document and Record Control

• Language: Must be available in English and may require Arabic translation upon request.
• Local QPPV: Must be appointed and responsible for the PSMF, ensuring it reflects KSA-specific PV activities.
• Submission:

The MAH shall maintain and make available on request a copy of the PSMF. The MAH must submit the copy within 7 days at the latest after receipt of the request from the SFDA. The PSMF should be submitted in a readable electronic format or clearly arranged printed copy.

The PSMF should not routinely be requested during the assessment of new marketing authorization applications (i.e. pre-authorization), but may be requested on an ad hoc basis, particularly if a new pharmacovigilance system is being implemented, or if product specific safety concerns or issues with compliance with pharmacovigilance requirements have been identified.

Special situation of the Multinational MAH in Saudi Arabia

For the Multinational MAH/Applicant the following two documents are required to have:

1. The PSMF (according to European Good Pharmacovigilance Practice which is the base for this guideline) and,
2. National pharmacovigilance sub-system file (national PSSF) which describes the key elements of pharmacovigilance activities in the KSA.

The PSSF:

The national pharmacovigilance sub-system file (national PSSF) shall include information and documents to describe the pharmacovigilance sub-system at the national level.

The content of the national PSSF shall be indexed to allow for efficient navigation around the document and follow the modular system described in the following sections and the annex.

The national PSSF shall be maintained in a KSA and be permanently available to the QPPV.

The PSSF structure is the same as the PSMF structure but in a localised level

• National PSSF section on “QPPV”
• National PSSF section on Organizational structure of the marketing authorization holder’s Local offices
• National PSSF section on Sources of safety data
• National PSSF section on Computerized system and databases
• National PSSF section on Pharmacovigilance processes
• National PSSF section on Pharmacovigilance sub-system performance
• National PSSF section on Quality system
• Annexes
  • Annex A, The QPPV for national pharmacovigilance sub-system
  • Annex B Organizational Structure of the MAH,
  • Annex C Sources of safety data,
  • Annex D Computerized systems and Databases,
  • Annex E Pharmacovigilance Process, and written procedures,
  • Annex F Pharmacovigilance Sub-System Performance,
  • Annex G Quality System,
  • Annex H Products,
  • Annex I Document and Record Control

Distinctive Features in KSA

• Product-Specific Monitoring: Greater emphasis on local product safety data and signal detection
• Local Contracts & PV Agreements: PSMF must reference agreements with local distributors or service providers
• Reporting Timelines: Reflect local case reporting and periodic safety update report (PSUR) obligations

4. Comparative Analysis: EU vs. KSA

5. Best Practices for Global Compliance

To ensure a seamless and compliant approach across both regions:

• Maintain a Global PSMF that aligns with GVP Module II.
• Create Country-Specific Annexes or Local PSMFs reflecting local requirements.
• Ensure Local Oversight by assigning competent local QPPVs.
• Implement a Centralized PV System that allows traceability and audit readiness across regions.
• Regularly Update and Audit both global and local PSMFs to reflect real-time changes.

Key Takeaways

• The PSMF is a regulatory requirement in both the EU and KSA, but implementation differs.
• The EU focuses on a centralized system overseen by the EU QPPV, while KSA mandates a local version managed by a locally appointed QPPV.
• KSA’s requirements include localization, Arabic translation (if requested), and proactive submission in some cases.
• MAHs must maintain up-to-date and inspection-ready PSMFs that reflect both global standards and local regulations.
• Harmonizing global and local PV practices is key to regulatory success and patient safety.

Authored By : Lamees El-Heeny
Head of Pharmacovigilance, Baupharma.