PSMF and pharmacovigilance inspections

Pharmacovigilance system master file

The pharmacovigilance system of a marketing authorisation or exemption holder for veterinary medicinal products or a registration holder for veterinary homeopathic products must be described in detail in a pharmacovigilance system master file (PSMF) since 28 January 2022 with the application of Regulation (EU) 2019/6. According to Article 87(5) of Regulation (EU) 2019/6, registration holders, have the same obligations as a marketing authorisation holder, subject to Article 2 (5), as do exemption holders according to Article2 (4) in conjunction with Article 5 (6). When the marketing authorisation holder is referred to in the following registration holders or exemption holders are therefore included. Exceptions are explicitly stated.

Content, structure, maintenance and location of the PSMF are specified in more detail in the respective Implementing Regulation (EU) 2021/1281, Articles 22, 24 and 25.

The PSMF shall be kept by the marketing authorisation holder in such a form that it is searchable, accessible at all times and also available in a structured, printed version on request.

According to Article 79(6) of Regulation (EU) 2019/6, the BVL may at any time request the marketing authorisation holder to submit a copy of the PSMF. This shall be provided within seven days of receipt of the request.

As part of an application for a marketing authorisation, a summary of the PSMF must be submitted with the dossier in accordance with Article 8 (1) letter c of Regulation (EU) 2019/6, this does not apply to applications for registration or for exemption from the marketing authorisation requirement. According to Article 23 of the Implementing Regulation (EU) 2021/1281, the summary of the PSMF shall contain the following information:

the reference number for the PSMF to be assigned by the authorisation holder;
the location of the PSMF;
Name, contact details and place of operation of the Qualified Person for Pharmacovigilance (QPPV);
the signed statement referred to in Article 22 (2) letter b, point (i) confirming that the qualified person for pharmacovigilance has the necessary means to perform the tasks and duties referred to in Regulation (EU) 2019/6
the type of record management system used for adverse event reports, including the name of the database used, if applicable.

Changes to the information contained in the summary of the PSMF must be reported in the form of variations not requiring assessment (VNRA).

You can find more information here (German only).

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Pharmacovigilance inspections

As the respective competent authority, the BVL controls and inspects in accordance with Article 79 (4) Regulation (EU) 2019/6 whether the marketing authorisation holders comply with the legal requirements for pharmacovigilance. According to Article 87 (5) of Regulation (EU) 2019/6, registration holders have the same obligations as marketing authorisation holders, subject to Article 2 (5), as do exemption holders according to Article 2 (4) in conjunction with Article 5 (6). When marketing authorisation holder is referred to in the following registration holders or exemption holders are therefore included. Exceptions are explicitly stated.

Marketing authorisation holders are often the first to become aware of adverse events (AEs) relating to veterinary medicinal products, as the treating veterinarians usually report such events directly to the marketing authorisation holder of the product used. Marketing authorisation holders are obliged to document these events comprehensively and to report all suspected adverse events to the Union Pharmacovigilance Database (UPhVD), as well as to coordinate any necessary risk minimisation measures.

The collection of these spontaneous reports of adverse events following the use of a veterinary medicinal product is an important tool for gaining further information about the veterinary medicinal products and in particular for detecting rare AEs. The BVL carries out pharmacovigilance inspections in order to check whether the marketing authorisation holders have established a pharmacovigilance system fit for purpose and whether this system is comprehensively described in a pharmacovigilance system master file (PSMF). In this way, it is checked whether the marketing authorisation holders comply with the legal obligations.

Within the scope of the these inspections, the BVL is entitled to inspect the PSMF, the pharmacovigilance system described therein and the risk management system of the marketing authorisation holder.

You can find more information here (German only).

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Legal basis

The obligations of the marketing authorisation holder with regard to pharmacovigilance are clearly described in Article 77 of Regulation (EU) 2019/6. Additionally, Article 78 specifies the actual tasks of the qualified person responsible for pharmacovigilance (QPPV) designated by the marketing authorisation holder. According to Article 87 (5) of Regulation (EU) 2019/6 registration holders have the same obligations as a marketing authorisation holder, subject to Article 2 (5), as do exemption holders according to Article 2 (4) in conjunction with Article 5 (6). When marketing authorisation holder is referred to in the following, registrations holders or exemption holders are therefore included. Exceptions are explicitly stated.

According to Article 79 (4) of Regulation (EU) 2019/6, the BVL as national competent authority is obliged to check, by means of controls and inspections referred to in Article 123 and Article 126, whether the marketing authorisation holders comply with the legal requirements for pharmacovigilance.

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Process

According to Article 126 (4) of Regulation (EU) 2019/6, the BVL as supervisory authority, is responsible for inspection of the PSMFs located in Germany and the associated pharmacovigilance systems of the marketing authorisation and registration holders. The PSMF and the pharmacovigilance system of exemption holders are also inspected by the BVL as part of controls in accordance with Article 123 of Regulation (EU) 2019/6 in conjunction with Article 79 (4).

The focus within such pharmacovigilance inspections is on the review of the processes described in the PSMF. This includes, for instance, the examination of the company´s in-house information flow and the processing of safety-relevant data from various sources (veterinarians, studies, literature, etc.) all the way from the receipt of a report to the sending of the report to EMA and the signal management process, as well as the company´s contractual arrangements with third parties regarding pharmacovigilance and also communication with authorities and the public.

Content and outcome of the inspection are documented and finally summarised in a report assessing the pharmacovigilance system of the inspected entity. Whereupon the inspected company issues a corrective and preventative action plan (CAPA). Implementation of CAPA is subsequently monitored by the BVL as part of the follow-up of inspection.

According to Article 27 (2) of Implementing Regulation 2021/1281 the BVL is entitled, if deemed necessary, to carry out national inspections at marketing authorisation holders whose PSMF is not located in Germany, and to accompany inspections by competent authorities in other Member States in order to check the national processes of German marketing authorisation holders not having a PSMF in Germany.