It was July 2012 when the European Medicines Agency made it mandatory for all the marketing authorization holders (MAH) to maintain the Pharmacovigilance System Master File (PSMF) as per the GVP Module II. Until then, the document was a concise one and called as the detailed description of Pharmacovigilance system (DDPS). After the PSMF came into existence, the concept of DDPS was limited to the licence holders of Veterinary Medicinal Products in the European Economic Area (EEA) and the UK. This continued until January 2023, when the VGVP became effective and the DDPS was replaced by the PSMF, for the licence holders of Veterinary Medicinal Products.

In 2012 the concept of PSMF was restricted to the European Economic Area. However, as of today, the regulatory agencies in more than 60 countries have made it mandatory for the companies to maintain the PSMF.

When is the PSMF required to be submitted?

As PSMF is a bulky document, it is not routinely required to be submitted in the EEA. Some regulatory agencies may require that the MAH submits the first version of the PSMF, especially when the MAH is planning to establish commercial supplies to a particular country for the first time. Besides, there are certain situations where the regulatory agencies may request the full PSMF. This can happen:

1. Prior to the regulatory inspection
2. Major changes to the PHV System (E.g., M&A)
3. Critical /Major Observation during the last inspection, or history of non-compliance, or when there are specific concerns about the product safety profile
4. Ad-hoc request from the regulatory agency

PSMF Submission Timelines

Most of the regulatory agencies provide 7 calendar days to the MAH for submitting the PSMF. However some agencies may provide 14 days (E.g., Egypt, Ghana, Oman, South Africa, etc.) or more. At times, the agency may even request that the MAH submits the PSMF immediately. In Pakistan the first version of the PSMF is required to be submitted within 45 days. Besides, the MAH needs to submit the PSMF as and when there is an update. However, in case of pre-inspection request, the MAH needs to submit the PSMF within 14 days. There are certain regulatory agencies which expect the MAH to maintain the PSMF but not submit it!

Different Names – Similar Document

In India, the document is called as the PvMF or the Pharmacovigilance Master File. The concept of PSSF or the Pharmacovigilance Sub-System File exists in the Arab league countries. The MAH can maintain a common PSMF for the entire Arab league, along with country specific PSSF.

Global PSMF

The concept of Global PSMF exists in some countries. It is generally the EEA PSMF which the MAH can submit to some regulatory agencies along with the country-specific PSMF annex.

Change Controls

It is recommended to have change controls in place as and when the PSMF gets updated. This ensures traceability and also completeness of the document. At times it may be operationally difficult to update the PSMF when one has only 7 calendar days to raise change control and update the PSMF. However, this scenario is quite common during the regulatory inspections, where the MAH has no choice but to adhere to the request.

Summary of the Pharmacovigilance System (SPS)

As PSMF is administratively a bulky document, there is a need to have a concise document that could be submitted as and when required by the regulatory agency. This requirement is fulfilled by the SPS. An SPS is generally a supplementary document that does not require any submission fee. However, in Oman, a variation is required to be submitted if there is any change to the SPS.

●The contact details of the responsible person for Pharmacovigilance (QPPV or any other term by which this person is designated) In some countries, one needs to also provide the national ID, official nomination letter, and certificates. Some regulatory agencies even expect the evidence that the applicant (MAH) has at his disposal a qualified person responsible for pharmacovigilance;

●A statement signed by the authorized signatory of the MAH to the effect that they have the necessary means to fulfil the pharmacovigilance tasks and responsibilities as per GVP requirements;

●A reference to the location of the pharmacovigilance system master file. The PSMF can be located at the safety operations’ site or where the QPPV operates from. It acceptable to maintain the electronic version of the PSMF on the document management system. Only that the MAH needs to ensure accessibility from each of the locations.

In some countries the SPS is regarded as the Summary of PSMF. In Malaysia, this document is regarded as PVSS, that stands for Pharmacovigilance System Summary.

SPS but not PSMF: The concept of SPS exists even in countries like Australia that do not require a PSMF.

Audits and Inspections

At times, the MAH may consider a PSMF audit by the external contractor. This is primarily to ensure PSMF compliance and also because many companies get a major observation on the PSMF during the regulatory inspections. The common observations include:

1. Non-Availability of the PSMF
2. Incomplete PSMF
3. Incorrect information in the PSMF
4. The QPPV is unable to access the PSMF at all times

All countries that require a PSMF, also require a Qualified Person for Pharmacovigilance (QPPV). However vice-versa is not true. There are countries where QPPV is required but not the PSMF.