Veterinary pharmacovigilance inspections: Q&As
Table of contents
These Q&As are based on the Pharmacovigilance Inspectors Working Group's interpretation of Volume 9B of The Rules Governing Medicinal Products in the European Union – Guidelines on Pharmacovigilance for Medicinal Products for Veterinary Use.
Minimum expectations for marketing authorisation holders (MAHs) in implementing pharmacovigilance agreements with other parties involved in fulfilling veterinary pharmacovigilance obligations
In Volume 9B, Part I, Section 1.3 it is clearly stated that a MAH may transfer any or all of the pharmacovigilance tasks and functions, including the role of the qualified person for pharmacovigilance (QPPV), to (an)other person(s) or organisation(s), but the ultimate responsibility for the fulfilment of all pharmacovigilance obligations and the quality and integrity of this always reside with the MAH. In such cases, it is the responsibility of the MAH to ensure that detailed and clear documented contractual arrangements are in place between MAHs and persons or organisations involved in the fulfilment of pharmacovigilance obligations and to provide the national competent authorities and, if applicable, the Agency, with information on such arrangements in line with the requirements set out in Volume 9B, Part I, Chapter 2: “Requirements for pharmacovigilance systems, monitoring of compliance and pharmacovigilance inspections”.
The MAH should identify the major subcontracting arrangements it has for the conduct of its pharmacovigilance activities and the main organisations to which it has subcontracted these (in particular where the subcontracted activities relate to the role of the QPPV, the electronic reporting of adverse events, the main databases, signal detection, the compilation of periodic safety update reports, literature search, etc.).
According to Volume 9B, Part I, Section 2.3.3 e), links with other organisations such as co-marketing agreements and contracting of pharmacovigilance activities should be outlined in the detailed description of pharmacovigilance system (DDPS).
The MAH should have the means to verify:
- the quality of the services given by the contract acceptor (and any other subcontractor);
- his capacity to carry out the assigned tasks;
- that he has implemented a quality assurance and quality control system.
This verification may be carried out, for example, by on-site or “distant” audits. The contract should clearly state the MAH's right to perform audits. According to Volume 9B, Part I, Section 1.3 ”the contracted person(s) or organisation should implement quality assurance and quality control and should accept to be audited by or on behalf of the MAH”.
In order to ensure that pharmacovigilance activities managed by a MAH in collaboration with another party are carried out in compliance with existing legislation/guidelines, the agreement between the two parties should be formalised in a written contract.
A pharmacovigilance agreement is expected to be drawn up in the form of a contract, in accordance with the recommendations detailed below.
The contract should:
- as much as possible be written according to a standard format in use by the MAH, eventually including easy-to-read sections such as tables outlining the responsibilities of each of the parties in carrying out pharmacovigilance activities and annexes which contain information subject to more frequent review (such as the list of products to which the contract is applicable).
- always be edited/signed by the responsible people from both parties, dated and reviewed in time in order to keep them up-to-date. The QPPV should have oversight of all contractual arrangements regarding the pharmacovigilance system (Volume 9B, Part 1 Section 1.2.1).
- clearly make reference to the legal framework of veterinary medicinal products.
Contracts are expected to contain at least the following information:
- clear description of all contracted-out activities (e.g. the role of the qualified person for pharmacovigilance (QPPV), communication of adverse events, managing of databases, archiving of information, signal detection, PSUR compilation, literature search, etc.), and, for each of them, of the relevant responsibilities (usually summarized in tabular form);
- timelines for conducting each of the subcontracted activities (where applicable), including timelines for data transfer (the clock for expedited reporting starts - day 0 - as soon as the minimum information, has been brought to the attention of any personnel of the MAH or an organisation having a contractual arrangement with the MAH concerning the conduct of pharmacovigilance - see Volume 9B, Part I, Section 4.5 “Required information for adverse event reports”);
- list of veterinary medicinal products covered by the contract (usually included as an appendix);
- provision that any activity subcontracted by the contract acceptor should be approved by the MAH;
- provision that the MAH is entitled to carry out audits of the contract acceptor and any other subcontractor;
- provisions linked to the termination of the contract (how to manage the contracted-out activities in this case);
- provisions linked to training (how and by whom training of the contracted-out activities is managed);
- in cases of contractual arrangements between MAHs in relation to co-marketing of separately authorised veterinary medicinal products, which are identical in all aspects except in their invented names, these arrangements should include measures to avoid the duplicate submission of adverse events toEudraVigilance Veterinary (Volume 9B, Part I, Section 1.3.).
Minimum expectations for the pharmacovigilance training of staff in veterinary pharmaceutical companies
Staff involved to any extent in pharmacovigilance activities should be trained at an appropriate level and on a continuous base in pharmacovigilance. Moreover, training should always be provided after any change which affects the pharmacovigilance system (organization, procedures, etc).
The process of training for all staff should be described in writing (e.g. in a standard operating procedure).
Qualified person for pharmacovigilance (QPPV)
An “appropriately qualified” QPPV should have a scientific background, best it would be a veterinarian with experience in the field of veterinary medicinal products (VMPs).
The QPPV is expected to have adequate knowledge in veterinary pharmacovigilance. This is normally achieved by attending a basic (initial) training followed by participation to (best external) training events on pharmacovigilance performed on a continuous base (the recommendation is at least once a year).
Documented evidence that the QPPV is keeping constantly updated on pharmacovigilance (legislation, procedures, guidelines, etc.) is also normally recognised appropriate as proof of the fulfilment of training requirements of the QPPV
Pharmacovigilance dedicated staff is expected to have adequate knowledge in veterinary Pharmacovigilance. This is normally achieved by attending a basic (initial) training followed by participation to (best external) continued events on pharmacovigilance performed on a continuous base (the recommendation is at least once a year).
Documented evidence that pharmacovigilance dedicated staff is keeping constantly updated on pharmacovigilance (legislation, procedures, guidelines, etc.) is also normally recognised as appropriate as proof of the fulfilment of training requirements of pharmacovigilance-dedicated staff.
Other MAH staff*
Initial training, followed by a periodic refresher training, is considered appropriate for all staff who could possibly come in contact with adverse events. The frequency of the periodic training should be evaluated on a case by case basis.
The above mentioned training has to include: (i) the recognition of adverse events including lack of efficacy, (ii) the collection of minimum information for adverse event reports and (iii) the importance of timely forwarding the information to the appropriate person.
*e.g. sales representatives, telephone operators, product managers, field trial/clinical research staff, other MAH staff who could first come in contact with adverse events.
The above interpretation of training needs is based on the requirements identified in the following sections of Volume 9B:
- “Staff should be appropriately trained for performing pharmacovigilance related activities, taking into account their role within the company. This includes not only staff within the pharmacovigilance units but also staff who may receive or process safety reports, such as sales personnel, or field trial/clinical research staff.” (Volume 9B, Part I, Section 2.3.3 f)
- “The QPPV should be appropriately qualified with documented experience in all aspects of pharmacovigilance […]. If the QPPV is not a veterinarian, access to a person qualified in veterinary medicine should be available.” (Volume 9B, Part I, Section 1.2)
- “The QPPV should have oversight of […] training of personnel in relation to pharmacovigilance.” It has to be ensured, that ad hoc training for new information is performed. (Volume 9B, Part I, Section 1.2.1)
The MAHs should ensure this by including external staff in their internal training programs or by carrying out audits.
Relevant contracts should include the training requirements of external staff and the MAH's right to audit them.
According to Volume 9B:
- “If pharmacovigilance obligations are devolved, a contractual agreement has to be in place. The ultimate responsibility for the fulfilment of all pharmacovigilance obligations and the quality and integrity of this always resides with the MAH.” (Part I, Section 1.3.)
- “The MAH has to ensure, that the staff of the contractor is adequately trained and any party carrying out pharmacovigilance activities in whole or in part, on behalf of, or in conjunction with, the MAH may be inspected.” (Part I, Section 2.5.7)
Documents demonstrating the title, the date, the lecturer, the participants, and the content of the training (e.g. training lecture notes, presentations or scripts for the participants) should be archived. The relation to pharmacovigilance for veterinary medicinal products should be apparent in the documents.
Not only the occurrence of a training should be documented, but also its effectiveness. Effectiveness could be documented, for example, by a test taken after the training. The training test and its outcome should be archived.
A document signed by the trainers, stating that the relevant trained staff has attended the training and understood its contents, should be available.
This whole training process should be described in writing (e.g. in a standard operating procedure).
The MAH should ensure that employees absent during a training event will get the opportunity to attend the same training on another date (as soon as possible).
A system should be in place to keep track of pending training. Training effectiveness should be ensured as mentioned in question 3.
This process should be described in writing (e.g. in a standard oeprating procedure).
If a given training has not proven to be effective for one or more participants, they should be retrained and should be given the possibility to clarify any residual doubts. Misunderstandings should be explained, all clarifications should be documented and the effectiveness of the training should be verified again.
In the case of an initial training or a training on new job duties, the trainee can only start his activity when the training has been considered effective.
This process should be described in writing (e.g. in a standard operating procedure).
Archiving can be paper-based or electronic.
If a company chooses to archive paper documents electronically, they should put in place a quality control of the process.
For data security and safe archiving, the same rules as for other pharmacovigilance documents apply (Volume 9B, Part I, Section 2.3.3 c), f) & g)).
In the detailed description pharmacovigilance system (DDPS), a brief description of the locations of the different types of pharmacovigilance source documents, including archiving arrangements, should be provided. Archiving should be performed according to a written procedure that also indicates where training records, CVs and job descriptions are filed.
The required duration of archiving is usually determined by national rules.
The MAH should ensure that the following evidence is readily available for inspection in order to give proof that staff involved in pharmacovigilance activities is properly trained:
- standard operating procedures (SOPs);
- list of employees involved with pharmacovigilance;
- staff job descriptions and CVs (at least for key personnel);
- training matrix (stating who gets which training and how often);
- training plan for individual employees;
- documents demonstrating the title and the content of the training, e.g. examples of training lecture notes or scripts for the participants (the relation to pharmacovigilance for veterinary medicinal products should become apparent from the documents.);
- proof of training effectiveness (e.g. training tests, and its outcomes);
- certificates of participation to external trainings;
- documented evidence that relevant persons are keeping constantly updated on pharmacovigilance legislation, procedures, guidelines etc, please refer to question 1 of this Q&A.