A pharmacovigilance system master file (PSMF) is a description of the pharmacovigilance system used by a marketing authorisation holder. The PSMF is part of the marketing authorisation holder's quality management system.
Although most marketing authorisation holders probably have one PSMF, it is possible for a marketing authorisation holder to have multiple pharmacovigilance systems, e.g. one for vaccines and biologics and another one for pharmaceutical products. Each system will have a different identification number and a different list of veterinary medicinal products.
The marketing authorisation holder will already have described its pharmacovigilance system for its veterinary medicinal products in a DDPS (Detailed Description of Pharmacovigilance System). Furthermore, the marketing authorisation holder will already have drawn up several SOPs (Standard Operating Procedures) with respect to pharmacovigilance and any quality management systems that may be in place. These documents will outline things such as the following:
policies
processes and procedures with regard to document management and risk management
personnel training, roles and qualifications
audits
change management
However, the regulation has also changed many processes with respect to pharmacovigilance.
Major changes in pharmacovigilance since 28 January 2022
Marketing authorisation holders no longer need to submit PSURs (periodic safety update reports). Instead, the marketing authorisation holder must continuously monitor the safety of its veterinary medicinal products by means of signal management. Regulation 2019/6 places responsibility for pharmacovigilance of veterinary medicinal products with the marketing authorisation holders.
The SOPs concerning signal management must be amended to ensure they meet the requirements outlined in Regulation 2019/6 and Commission Implementing Regulation 2021/1281. The marketing authorisation holder must perform at least one signal detection check per year in the EU's pharmacovigilance database, the so-called EudraVigilance Data Warehouse. A description must be provided of signal validation, prioritisation and assessment procedures. Furthermore, there must be guidelines as to when a signal must be forwarded to IRIS. More detailed information can be found in VGVP Guideline on Signal Management.
The recipient (be it the marketing authorisation holder or the national competent authority) must forward all reports to EudraVigilance. Reports of severe adverse events can be recorded in the EudraVigilance database directly; they need not be assessed by the Veterinary Medicinal Products Unit first. Reports of events that were considered non-severe prior to 28 January 2022 must now be forwarded to the pharmacovigilance database, as well.
No more than 30 days must elapse between the receipt of the report and its entry into the database.
Marketing authorisation holders are free to use the EU's pharmacovigilance database (EudraVigilance) as their own pharmacovigilance database. The personal data of persons who have reported an adverse event must be archived internally by marketing authorisation holders, because reports filed with EudraVigilance must be anonymised, since the EudraVigilance database does not meet the confidentiality requirements laid down in the GDPR.
The Implementing Act on Good Pharmacovigilance Practices describes in detail which requirements the PSMF and the relevant component of the quality management system must meet. It also outlines the requirements for a communication plan. In addition, it outlines which sections must be included in the PSMF. Also refer to the relevant EMA VGVP guideline.
Format of the PSMF
PSMFs are part of the marketing authorisation holder's quality management system and must consist of the following components (Article 22 of the Commission Implementing Regulation 2021/1281):
A main part that describes the pharmacovigilance system for the veterinary medicinal product, as well as annexes providing more detailed information.
The main part of the pharmacovigilance system master file must contain the following sections:
General information on the PSMF
PSMF reference number;
PSMF location for the purpose of pharmacovigilance inspections in accordance with Article 126(4) of Regulation (EU) 2019/6;
Information on the qualified person responsible for pharmacovigilance (QPPV), the assistant veterinary surgeon and the associated back-up procedures
Information on the qualified person responsible for pharmacovigilance including name, contact details and a signed statement from the marketing authorisation holder and the qualified person confirming that the qualified person concerned has the necessary means to fulfil the tasks and responsibilities required by Regulation (EU) 2019/6;
Documentation on the marketing authorisation holder arrangements concerning the assistant veterinary surgeon referred to in Article 3(2), if applicable, including the contact details;
A description of back-up arrangements that apply in the absence of the qualified person responsible for pharmacovigilance or the veterinary surgeon assisting the qualified person responsible for pharmacovigilance referred to in Article 2(6);
Information on the marketing authorisation holder
A detailed description of the organisational structure of the marketing authorisation holder, including a parent company or group of companies associated;
The position of the qualified person responsible for pharmacovigilance within the organisation.
A description of the document management system referred to in Article 5, including the record management system for adverse event recording referred to in Article 10;
A description of the quality management system for pharmacovigilance activities, including all of the following:
A description of the processes used for pharmacovigilance activities referred to in Article 4(3), (4), (5) and (6): basically, a description of the processes in place with regard to reports of adverse events and how to guarantee that these processes are performed properly. The description must contain the following information: a description of risk management processes, policies and procedures; a risk-benefit analysis, signal management and a communication plan.
A description of the training management system in place referred to in Article 6(2);
A description of the system used for documenting or archiving information referred to in Article 5(2);
A description of the system for monitoring the performance of the pharmacovigilance system as referred to in Article 7;
A description of the responsibilities for quality assurance auditing of the pharmacovigilance system as referred to in Article 8, including, where appropriate, auditing of sub-contractors;
A list of audits associated with unresolved critical or major findings;
A description of the corrective and preventive action plan (CAPA) management and change management in place as referred to in Article 9;
A description of the contractual arrangements between marketing authorisation holders and third parties concerning pharmacovigilance activities, where applicable.
3. The following documents must be appended to the PSMF:
A log book containing records of all changes to the main part of the pharmacovigilance system master file;
Additional information regarding the qualified person responsible for pharmacovigilance, the assistant veterinary surgeon and the associated back-up procedures;
- Curriculum vitae including information on qualifications and training of the qualified person responsible for pharmacovigilance as referred to in Article 3(1) and, if applicable, the assistant veterinary surgeon as referred to in Article 3(2);
- A description of the tasks and responsibilities of the qualified person responsible for pharmacovigilance;
- Proof of registration with the pharmacovigilance database (EudraVigilance);
- A list of the pharmacovigilance activities that have been delegated by the qualified person responsible for pharmacovigilance to third parties;
Additional information on the marketing authorisation holder:
- A list of all veterinary medicinal products covered by the pharmacovigilance system master file, including the international non-proprietary name (INN) of the active substances, if applicable, the member states in which the product is authorised or registered, the type of procedure for authorisation and the authorisation numbers in each member state where the product is authorised;
- A list of reference numbers for other pharmacovigilance system master files held by the same marketing authorisation holder, where applicable;
- A list of local or regional representatives for the purpose of receiving reports of suspected adverse events, including their contact details, responsibilities and territories, where applicable;
- A list of the sites where pharmacovigilance activities listed in Article 4(3), (4), (5) and (6) are carried out;
Further details about the quality management system
- A list of documents, policies, procedures and processes used for the pharmacovigilance activities referred to in Article 4(3), (4), (5) and (6);
- A list of all scheduled and completed audits, including outstanding critical and major findings;
- A list of performance indicators and how to use them, as referred to in Article 7, as applicable;
- The information on training plans and records referred to in Article 6(2);
- The methodology to calculate the factor referred to in Article 14(2), used to calculate incidence on the basis of sales data.
- A list of risk management measures and the outcome of risk mitigation measures;
Further information on contractual arrangements between marketing authorisation holders and third parties concerning pharmacovigilance activities:
- A list of the activities or services sub-contracted by the marketing authorisation holder to third parties to fulfil pharmacovigilance obligations and information on who the activities or services are sub-contracted to, including the name and address of any sub-contractors, where applicable;
- A list of the tasks of the qualified person responsible for pharmacovigilance referred to in Article 78 of Regulation (EU) 2019/6 that have been totally or partially outsourced and the information on who the activities or services are sub-contracted to, including the name(s) and address(es) of the sub-contractor(s), where applicable;
- A list of existing contracts and agreements with third parties, where applicable, including the products and territories concerned.
- Where appropriate, information may be provided in the form of charts or flow diagrams.
Summary of the PSMF
You no longer need to submit the complete description of the pharmacovigilance system when you submit a new application. All you need to submit when you submit your first application is the summary of the PSMF.
This summary must contain the following information:
The pharmacovigilance system master file (PSMF) reference number;
The pharmacovigilance system master file location;
Name, contact details and place of operation of the qualified person responsible for pharmacovigilance (QPPV);
The signed statement referred to in Article 22(2)(b), point (i); A signed statement by the marketing authorisation holder and the qualified person responsible for pharmacovigilance (QPPV) to the effect that the QPPV has the necessary means to fulfil the required tasks and responsibilities;
The type of record management system used for adverse events reports, including the name of the database, if applicable.
Since nowadays you only have to submit a summary of the PSMF, you no longer need to submit amendments whenever you make changes to the PSMF. In your capacity as the marketing authorisation holder, you must keep a log book of such amendments to the PSMF.
Please note: This Regulation has completely changed the rules governing veterinary pharmacovigilance. It is expected that the procedures will be clarified further over the next few years, and guidance documents will be supplemented or amended. As soon as this happens, we will amend the above text. You can find the latest information about the new pharmacovigilance rules on EMA's Pharmacovigilance website at any time.
