PSMF: pharmacovigilance system master file
The pharmacovigilance system master file (PSMF) is the holder's detailed description of its pharmacovigilance system, kept in the EU for inspectors.
Article 104(3)(b) of Directive 2001/83/EC requires every marketing authorisation holder to maintain and make available on request a pharmacovigilance system master file. Articles 1 to 7 and Annex I of Commission Implementing Regulation (EU) No 520/2012 set its content and structure, and GVP Module II explains how it is maintained. The file describes the QPPV and their deputy, the organisational structure of the holder, the sources of safety data, the computerised systems and databases, the pharmacovigilance processes, the performance indicators, the quality system, and, in its annexes, the lists of products covered, contracts with third parties, audits and a logbook of changes. The file must be located in the EU, either where the main pharmacovigilance activities are performed or where the QPPV operates.
A marketing authorisation application contains a summary of the pharmacovigilance system in Module 1.8.1, which gives the QPPV's details, the location of the master file and a statement that the holder has the necessary means to meet its obligations. The master file itself stays with the holder, and the authorities ask for it when planning or conducting an inspection, when assessing a change of QPPV or of the system, or when a safety concern arises. Each master file has a PSMF number assigned through the Article 57 database, and the same file can cover all the products of a holder or of a group of holders, provided the system is genuinely shared.
The document is living. Every change to the system, from a new safety database to a new contract with a distributor who collects adverse events, has to be reflected in the relevant section and recorded in the logbook with its date. A change of the master file location or of the QPPV is no longer a variation: since 2013 it is made by updating the Article 57 database record, which covers every product the file applies to.
What goes wrong: the master file describes an idealised system rather than the processes actually followed; annex lists of products and contracts are years out of date; the logbook is reconstructed before an inspection instead of kept; partner agreements say nothing about adverse event exchange timelines; and the summary in each marketing authorisation points at a master file location that has since moved. Inspectors compare the master file with the evidence, so gaps between the two are the most common critical or major finding.
Timing
Under Article 7 of Regulation (EU) No 520/2012 the holder must provide a copy of the master file within seven days of a request from a competent authority. Changes must be recorded in the logbook as they occur, and the annex lists are expected to be current at any time, not reconstructed when an inspection is announced.
Used in
Pharmacovigilance teams keep pharmacovigilance system changes tied to the obligations behind them in the obligation-to-action workflow.
Related terms
- QPPV: qualified person responsible for pharmacovigilanceThe QPPV is the named individual, resident in the EU, who is personally responsible for a marketing authorisation holder's pharmacovigilance system.
- EudraVigilance: EU adverse reaction databaseEudraVigilance is the EU system for collecting, managing and analysing suspected adverse reaction reports for medicines authorised in the EEA.
- xEVMPD: extended EudraVigilance medicinal product dictionary (Article 57 database)The xEVMPD, or Article 57 database, is EMA's record of every medicine authorised in the EU, which holders must keep updated within 15 days of changes.
- Type IAIN variation: minor change notified immediately after implementationA Type IAIN variation is a minor change the holder may implement first but must notify to the authority immediately afterwards, not in an annual update.
- MAH transfer: transfer of a marketing authorisation to a new holderAn MAH transfer moves a marketing authorisation from one legal entity to another, making the new company legally responsible for the product.
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