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Pharmacovigilance System Master File (PSMF) for European Medicines Agency (EMA) Medicinal Authorization Application in European Union

Updated: May 2

In the realm of pharmaceuticals, ensuring the safety of drugs is paramount. Pharmacovigilance, the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem, plays a crucial role in this process. One integral aspect of pharmacovigilance is the Pharmacovigilance System Master File (PSMF). The Pharmacovigilance System Master File (PSMF) is a comprehensive document mandated for all Marketing Authorization Holders (MAHs) seeking approval for medicinal products within the European Union (EU). The PSMF serves as a comprehensive document that goes beyond the confines of the EU, capturing global safety data for medicinal products. This means that MAHs must document not only regional or local safety information but also global safety data in the PSMF.

Pharmacovigilance System Master File PSMF EMA

Regulatory Basis of Pharmacovigilance System Master File (PSMF)

The legal framework mandating marketing authorization holders (MAHs) to maintain and provide a Pharmacovigilance System Master File (PSMF) finds its roots in

  • Directive 2010/84/EU and

  • Regulation (EU) No 1235/2010

  • Directive 2001/83/EC

  • Implementing Regulation (EU) No 520/2012.

This regulatory framework, supplemented by guidance in the Good Pharmacovigilance Practices (GVP) Module, sets the stage for comprehensive and standardized pharmacovigilance practices across the EU.

What is a Pharmacovigilance System Master File (PSMF) as per EMA?

The Pharmacovigilance System Master File (PSMF) is a comprehensive document that provides an overview of the pharmacovigilance system implemented by a marketing authorization holder (MAH) or sponsor of a medicinal product. It serves as a centralized repository of information pertaining to pharmacovigilance activities associated with a specific medicinal product or a group of products marketed by the same MAH. It encompasses global, regional, and local safety data for authorized medicinal products. 

Who should develop and maintain Pharmacovigilance System Master File (PSMF)?

The requirement for a PSMF extends to all medicinal products authorized in the EU, regardless of whether they underwent the centralized or decentralized procedure. However, there are specific considerations for different categories of medicinal products.

  • Traditional Herbal Medicines: For products registered under the simplified registration process for traditional herbal medicines, the summary of the pharmacovigilance system is not required as part of the marketing authorization application. Nonetheless, MAHs are obligated to operate a pharmacovigilance system and maintain a PSMF, which must be available for submission upon request. For herbal medicines that do not fall within the scope of traditional-use registration, the requirements for operating a pharmacovigilance system, maintaining a PSMF, and submitting a summary of the pharmacovigilance system apply.

  • Homeopathic Medicinal Products: Homeopathic medicinal products registered via the simplified registration procedure are exempt from the requirement to submit a summary of the pharmacovigilance system. However, MAHs must still operate a pharmacovigilance system, maintain a PSMF, and make it available upon request. For other homeopathic medicinal products falling outside the scope of simplified registration, the full requirements for pharmacovigilance system operation, PSMF maintenance, and summary submission apply.

When should a Marketing Authorization Holder prepare Pharmacovigilance System Master File (PSMF) for EMA?

A Marketing Authorization Holder (MAH) should prepare the Pharmacovigilance System Master File (PSMF) as part of their regulatory obligations during the pre- and post-authorization phases of a medicinal product. The preparation of the Pharmacovigilance System Master File (PSMF) begins during the marketing authorization application process and continues throughout the lifecycle of the medicinal product, with ongoing maintenance and updates as necessary to ensure compliance with regulatory requirements. Here's a breakdown:

Pre-Authorization Phase:

  • During Marketing Authorization Application: The MAH should begin preparations for the PSMF during the marketing authorization application process. This includes outlining the pharmacovigilance system that will be implemented for the product and ensuring that the necessary infrastructure, personnel, and procedures are in place. The summary of the Pharmacovigilance system must be included under Module 1.8.1 of the medicinal product technical Dossier.

  • Submission of PSMF Information: As part of the marketing authorization application, the MAH must provide information about the location of the PSMF and demonstrate compliance with pharmacovigilance regulations. The Pharmacovigilance System Master File (PSMF) must be readily accessible for submission upon request during the evaluation of the application.

Post-Authorization Phase

  • Upon Receipt of Marketing Authorization: Once the marketing authorization is granted, the MAH must finalize and maintain the PSMF. This involves documenting the established pharmacovigilance system, including organizational structure, procedures, and risk management plans.

  • Ongoing Maintenance: The MAH is responsible for continuously updating the PSMF to reflect any changes or updates to the pharmacovigilance system. This includes revisions to procedures, organizational changes, updates to risk management plans, and any other relevant information.

  • Notification of Changes: Any significant changes to the pharmacovigilance system or the PSMF itself must be promptly communicated to the relevant regulatory authorities and the Qualified Person Responsible for Pharmacovigilance (QPPV).

Location of the Pharmacovigilance System Master File (PSMF)

 Determining the appropriate location for the Pharmacovigilance System Master File (PSMF) is a critical aspect of regulatory compliance for marketing authorization holders (MAHs) operating within the European Union (EU). As per regulatory requirements, the PSMF should be situated either at the site in the EU where the main pharmacovigilance activities of the MAH are conducted or at the location where the qualified person responsible for pharmacovigilance (QPPV) operates. This ensures that the PSMF remains readily accessible for review and inspection by regulatory authorities, facilitating transparency and accountability in pharmacovigilance practices.

 Electronic Format and Accessibility of Pharmacovigilance System Master File (PSMF)

In line with regulatory directives, the Pharmacovigilance System Master File (PSMF) may be maintained in electronic form, provided that a clearly arranged printed copy can be readily produced upon request by competent authorities. Regardless of format, the PSMF must adhere to stringent standards of legibility, completeness, and accessibility to ensure effective oversight of pharmacovigilance activities. To facilitate easy navigation and traceability, the PSMF should be indexed meticulously, enabling swift retrieval of pertinent information. While electronic book-marking and searchable text are encouraged for enhanced usability, the inclusion of embedded documents is generally discouraged to maintain clarity and transparency. Additionally, specific measures may be necessary to restrict access to the PSMF, ensuring controlled management of content and assigning clear responsibilities for change control and archiving. Appendices containing documents such as signed statements or agreements should be incorporated and appropriately referenced in the index for comprehensive documentation and audit readiness.

Language Requirements for Pharmacovigilance System Master File (PSMF)

Primarily, the PSMF should be written in English, unless the marketing authorization holder exclusively holds approvals in a single Member State, in which case it can be written in the official language of that territory within the European Union (EU). Additionally, the PSMF should be indexed in a manner consistent with the headings described in relevant regulatory modules, allowing for easy navigation and retrieval of information. By meeting these language standards, MAHs facilitate effective communication and regulatory compliance, enhancing transparency and accountability in pharmacovigilance activities within the EU.

Components of a Pharmacovigilance System Master File (PSMF)

  • Company Information: This section includes details about the MAH or sponsor, such as company name, address, contact information, and responsible personnel for pharmacovigilance activities.

  • Description of Pharmacovigilance System: Here, the document outlines the pharmacovigilance system implemented by the MAH, including organizational structure, roles and responsibilities, procedures for collecting, processing, and reporting adverse drug reactions (ADRs), signal detection activities, risk management plans, and measures for ensuring compliance with regulatory requirements.

  • Pharmacovigilance Activities: This section provides detailed information about various pharmacovigilance activities conducted by the MAH, such as ongoing safety monitoring, periodic safety update reports (PSURs), risk management plans (RMPs), post-authorization safety studies (PASS), and risk minimization measures.

  • Quality Management System (QMS): A robust QMS is essential for ensuring the reliability and integrity of pharmacovigilance data. The PSMF includes information on the QMS implemented by the MAH, including procedures for data collection, validation, documentation, and archiving.

  • Audits and Inspections: Details of audits and inspections conducted by regulatory authorities or third-party organizations are documented in this section, along with any corrective and preventive actions (CAPAs) taken in response to audit findings.

  • Changes and Updates: The PSMF should be regularly reviewed and updated to reflect changes in the pharmacovigilance system or regulatory requirements. This section outlines the process for making changes to the PSMF and ensuring its accuracy and completeness.

Pharmacovigilance System Master File PSMF EMA

*The ToC is created for representational purposes. Contact Artixio in case of any concerns

Change Management: Ensuring Compliance and Transparency

The Pharmacovigilance System Master File (PSMF) is a dynamic document subject to ongoing changes to reflect evolving pharmacovigilance requirements and operational adjustments. Effective change management is crucial to maintain regulatory compliance and ensure the integrity of pharmacovigilance activities. MAHs are mandated to promptly communicate routine and significant changes to the Qualified Person Responsible for Pharmacovigilance (QPPV). These changes encompass updates to the PSMF content or its location, addition of corrective or preventative actions, changes in content to meet oversight criteria, alterations in arrangements for providing the PSMF to competent authorities, outsourcing of pharmacovigilance services, and inclusion of new products into the pharmacovigilance system. Notably, changes that may impact workload or product responsibilities should also be promptly reported. It is imperative that any recipient QPPV explicitly accepts these changes in writing to ensure accountability and clarity. Ultimately, the QPPV plays a pivotal role in verifying the accuracy and currency of information contained within the PSMF, thereby upholding the integrity of the pharmacovigilance system under their responsibility. Effective change management practices underscore the commitment of MAHs to transparency and regulatory compliance in pharmacovigilance operations.

Pharmacovigilance System Master File PSMF EMA

*The ToC is created for representational purposes. Contact Artixio in case of any concerns

In the dynamic landscape of pharmaceutical regulation, the Pharmacovigilance System Master File (PSMF) stands as a cornerstone of drug safety. Mandatory for all medicinal products authorized in the EU, the PSMF encapsulates the comprehensive pharmacovigilance system implemented by MAHs. By adhering to regulatory requirements and promptly addressing changes, MAHs uphold their commitment to safeguarding public health and ensuring the integrity of medicinal products throughout their lifecycle. 

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