II.B.5 Change control, logbook, versions and archiving

It is necessary for marketing authorisation holders to implement change control systems and to have robust processes in place to continuously be informed of relevant changes in order to maintain the PSMF accordingly. The competent authorities may solicit information about important changes to the pharmacovigilance system, such as, but not limited to:

• Changes to the pharmacovigilance safety database(s), which could include a change in the database itself or associated databases, the validation status of the database as well as information about transferred or migrated data;
• Changes in the provision of significant services for pharmacovigilance, especially major contractual arrangements concerning the reporting of safety data;
• Organisational changes, such as takeovers, mergers, the sites at which pharmacovigilance is conducted or the delegation/transfer of PSMF management.

In addition to these changes being documented in the PSMF for the purpose of change control (in the logbook), the QPPV should always been kept informed of these changes.

Changes to the PSMF should be recorded, such that a history of changes is available (specifying the date and the nature of the change), changes to the PSMF must be recorded in the logbook described in Article 5(4) of Commission Implementing Regulation No 520/2012. Descriptive changes to the content of the master file must be recorded in the logbook.

Change history for the information contained in the Annexes may be ‘on demand’, in which case the logbook would indicate the date of the revision of PSMF content and/or Annex update(s), the history of changes for Annex content would also be updated. Information that is being regularly updated and is contained in the Annexes, such as product and standard operating procedure lists or compliance figures, may include outputs from controlled systems (such as electronic document management systems or regulatory databases). The superseded versions of such content may be managed outside of the PSMF content itself, provided that the history of changes is maintained and available to competent authorities and the Agency on request. If the PSMF has not been requested, or has remained unchanged for a period of time (for example, if the changes in the content of Annexes are managed outside of the PSMF), it is recommended that a review is conducted periodically. Marketing authorisations holders need to ensure that the obligations concerning the timely provision of the PSMF can be met. It is also noted that the QPPV must be able to gain access to current and accurate information about the pharmacovigilance system, hence permanent access to the PSMF must be enabled, including the information contained in the Annexes (either via the pharmacovigilance master file itself or via access to the systems used to generate the Annex content).

Marketing authorisation holders should be able to justify their approach and have document control procedures in place to govern the maintenance of the PSMF. As a basis for audit and inspections, the PSMF provides a description of the pharmacovigilance system at the current time, but the functioning and scope of the pharmacovigilance system in the past may need to be understood.

Changes to the PSMF should also account for shared pharmacovigilance systems and delegated activities. A record of the date and nature of notifications of the changes made available to the competent authorities, the QPPV and relevant third parties should be kept in order to ensure that change control is fully implemented.

The PSMF should be retained in a manner that ensures its legibility and accessibility [IR Art 5 and Art 7].