Pharmacovigilance System Master File

The Pharmacovigilance System Master File (PSMF) is a detailed collection of information that specifies all aspects related to how a pharmaceutical company is conducting pharmacovigilance. The purpose with the PSMF is first to provide the QPPV with a constantly updated oversight with the Pharmacovigilance System and in addition to ensure that all regulatory and company requirements are met.
It is also a tool for planning and conduct of internal audits of the separate components of the pharmacovigilance. Lastly of cause it is a tool for the competent authorities to get a quick overview of how the pharmacovigilance system works in a company that holds a marketing authorization in EU. This is for instance needed for the competent authorities when they are planning and conducting inspections.
The information in the PSMF spans a great variety of information from procedures, policies, guidelines, staff training and compliance to IT systems structure and validation.
The term Pharmacovigilance System Master File was introduced first in the 2010 revision of the 2001/83/EC European Union Directive identified as 2010/84/EU as well as Regulation 1235/2010 which jointly govern pharmacovigilance activities in the EU.
In Article 1(28e) the PSMF is defined as:
Pharmacovigilance system master file: A detailed description of the pharmacovigilance system used by the marketing authorisation holder with respect to one or more authorised medicinal products.’.
So it is defined as a detailed description which it also is at least in the summary of the pharmacovigilance system, but in practical terms most of the PSMF is a collection of information stored and maintained in many different place in a company.
It is the intention to have only one PSMF in a company, but there can be situations where two or more may be appropriate. Splitting the PSMF up in several separate PSMFs can be relevant if the company sells products of very different nature like for instance both pharma products and vaccines. Normally though it is much simpler to have only one PSMF.
When setting up a PSMF it is important to go through the list of items that have to be included in detail and note where the information will come from and who is responsible for maintenance as a regulatory agency can request access to an updated version with short notice (max 7 days). You have to ensure that all components are continuously updated at predefined intervals. When an agency request the information there won’t be time to start updating it has to be pretty much immediately ready.

PSMF main body

The PSMF consist of a main body that is structured according to the headings described in GVP module II and some of the information will be separated out in annexes dependent on how and where the particular information is updated. So for instance information about CAPAs would be in the CAPA system and information about reporting compliance could be in the safety system etc. The key is that the QPPV have instant access to all components of the PSMF at any time and that an extract can be provided to a regulatory agency within 7 days.
Note that the PSMF location and contact details will be made public via the agency web-portal for transparency and communication purposes

PSMF Annexes

Annexes can include the following in a typical PSMF
B) PSMF location and registration information
C) Company Organization Structure
D) Safety Data Sources
E) IT systems and Databases
F) Pharmacovigilance process documents, policies and work instructions
G) Pharmacovigilance System Performance
H) Quality Management System
I) Product and registration listings
J) Logbook of changes

The development and maintenance of the PSMF must be described in a specific PSMF Standard Operating Procedure and the contents of the PSMF must be retained for 30 years.
Just managing the PSMF and controlling the distribution of a document with multiple sources can be a daunting task. Often companies utilize technologies like SharePoint, Office 360 or Google Docs in order to keep track of versioning of the different information components/annexes. Each of these with own benefits and risks, so here also a need for careful planning.
For most organizations there is a need for at least one dedicated coordinator to maintain the information in the PSMF and to ensure that everything is compliant and up to date. Normally this the PSMF function will report directly to the QPPV.
The coordinator will also serve as the contact point for all the different functions in a pharmaceutical company that are stakeholders in the information contained in the PSMF which will include the following function in a big pharmaceutical company. Smaller companies have to cover the same information but they usually have some of the below functions merged into one:

  • Regulatory Affairs
  • Regulatory Operations
  • Labeling
  • Medical Information
  • Clinical Development
  • Clinical Operations
  • Local Operating Companies
  • Local QPPV functions
  • Corporate Quality/Auditing
  • Inspection Management
  • Legal
  • Training
  • Safety IT
  • Procurement
  • Safety Operations
  • Medical Review
  • Global Safety Officers
  • QPPV office

PSMF continuously updated

In order to keep the PSMF updated so it can be provided in 7 days or less it is necessary to have routine update sequences for each of the components of the PSMF. Normally such routine updates would be done on a quarterly basis. Significant changes for instance in the form of changed contracts, new database or big organizational changes the PSMF must be updated immediately and ad hoc. Such ad hoc updates can also be triggered by a request by a regulatory agency, but normally you would have to stick with what you have from the latest routine update (quarterly) as it would be almost impossible to make a full update within a 7 day timeframe.

QPPV sign-off

Each time the PSMF is updated the QPPV must sign off to document that the QPPV is aware of the most recent changes. This sign off can be on paper or appropriate electronic means, but the big challenge is for the QPPV to determine what has to be reviewed as the amount of data usually prohibit a full review of the details of all changes.