1. The document management system referred to in Article 5 shall include a record management system for receiving, recording, collating and assessing information on adverse events and for recording safety information.
2. The description of the record management system for recording adverse events and safety information in Section D of the pharmacovigilance system master file shall include the following information:
(a)
type of record management system used for adverse event reports, including the name of the database used, if applicable;
(b)
location where the record management system is kept;
(c)
description of functionality of the record management system;
(d)
operational responsibility of the personnel responsible for the record management system;
(e)
summary of the assessment of its fitness for purpose.
3. Marketing authorisation holders may use the Union pharmacovigilance database as their electronic record management system for recording adverse events. In that case, Section D of the Pharmacovigilance system master file shall indicate that the record management system being used is the Union pharmacovigilance database.
Marketing authorisation holders shall collect and maintain detailed records of all suspected adverse events from all sources within or outside the Union in accordance with Article 77(1) of Regulation (EU) 2019/6. Those records shall include post-marketing surveillance studies and literature relating to their veterinary medicinal products, and suspected adverse events concerning use of their veterinary medicinal products outside the terms of the marketing authorisation.
1. Information concerning suspected adverse events shall be recorded and coded using internationally agreed standards. The latest version of the standards shall be used in line with the specified implementation dates.
2. Records of adverse events shall include at least the following:
(a)
an identifiable reporter or source (including the country code);
(b)
details of identifiable animals, humans or environment;
(c)
veterinary or human medicinal product names;
(d)
details on the adverse events.
3. Where the name of the product is not included in the initial report from the primary source, marketing authorisation holders shall make reasonable efforts to obtain the name or at least part of the trade name of the medicinal product concerned. If neither the name nor the trade names are known and cannot be obtained, the name of the active substances shall be recorded in the record management system.
4. Marketing authorisation holders shall make reasonable efforts to request further information, as necessary, to enable investigation of suspected adverse events, including the results of appropriate diagnostic tests, to ensure that adverse event data reported are complete.
Adverse event recording in the Union pharmacovigilance database
1. Marketing authorisation holders shall record adverse events in the Union Pharmacovigilance database.
2. A language customary in the field of medical science shall be used to record non-coded information in the Union pharmacovigilance database, including such information related to adverse events originating outside the Union.
3. Marketing authorisation holders shall regularly monitor the scientific literature to identify any adverse events concerning their veterinary medicinal products. The method for monitoring literature and the frequency with which monitoring is conducted shall take into account the risk-based approach. It shall at least cover the following topics: active substance, type of product, the stability in number and incidence of reports observed over time on the market and the stability of the pharmacovigilance profile.
1. To enable comprehensive analysis of adverse event reports from third countries, marketing authorisation holders shall record in the Union product database the corresponding product names and authorisation numbers for the same product or, if the same product is not authorised in the Union, for a similar product authorised in the Union, as defined in the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) Guideline 24 ( 3 ) . Marketing authorisation holders shall update the information when necessary.
2. The total number of animals displaying an adverse event during a defined period of time, multiplied by 100 and divided by an estimate of the number of animals treated during that period, shall provide the incidence of reported adverse events. To calculate the estimated number of animals treated from the information on volume of sales required under Article 58(12) of Regulation (EU) 2019/6, marketing authorisation holders shall identify and provide a factor to the Union product database for each of their veterinary medicinal products according to country, target species and pack size. According to the posology of the product, the factor will determine how many animals can be treated with one package of a given pack size, regardless of the formulation. To calculate the incidence for adverse event reports from third countries via the estimated number of animals treated, marketing authorisation holders shall provide information on volume of sales for each of their veterinary medicinal products, combined for all third countries according to target species, and in regard to the same or a comparable pack size.
3. The Agency shall publish guidance on the mathematical formula to calculate the factor. Marketing authorisation holders shall record their assumptions on distribution of sales per target species and treatment regimen per target species that they use for the calculation of the factor in the pharmacovigilance system master file. Marketing authorisation holders shall update the factor when necessary.
1. Post-marketing surveillance studies may be conducted by marketing authorisation holders on their own initiative or shall be conducted by marketing authorisation holders on request of a competent authority or the Agency in accordance with Article 76(3) and (4) of Regulation (EU) 2019/6.
2. Voluntary post-marketing surveillance studies shall be notified to the responsible competent authority or the Agency immediately after initiation. The marketing authorisation holder shall submit the protocol and the final report within one year after completion of the data collection to the competent authority or the Agency, as applicable.
3. For a requested post-marketing surveillance study, the marketing authorisation holder shall submit the draft study protocol to the competent authority or the Agency who requested the study, as applicable, for approval at the latest two months before the trial is conducted.
4. The marketing authorisation holder shall notify the competent authority of the territory in which the post-marketing surveillance study is conducted, where that competent authority did not request the study.
5. The marketing authorisation holder shall submit the study protocol, the summary of the final study report and the final study report after finalisation of the study to the competent authority or the Agency who requested the post-marketing surveillance study, as applicable, and to the competent authority of the territory in which the study was conducted.
6. The marketing authorisation holder shall submit all relevant documents in a language customary in the field of medical science, except for studies to be conducted for veterinary medicinal products that are authorised only in one Member State. For those studies, the marketing authorisation holder shall provide a translation of the title, the summary of the study protocol and a summary of the final report of the study in a language customary in the field of medical science.
7. The marketing authorisation holder shall ensure that all information concerning the study is handled and stored in such a way that it can be correctly reported, interpreted and verified. The marketing authorisation holder shall ensure that the analytical dataset and statistical programmes used to generate the data contained in the final report of the study are stored electronically and are available for audits and inspections upon request of the competent authority or the Agency, as applicable.
1. Marketing authorisation holders shall ensure that the pharmacovigilance system includes a risk management system to take appropriate action to minimise identified risks, when necessary.
2. The risk management system shall include a process for monitoring the benefit-risk balance of products and performing signal management. It shall also include a communication system in accordance with Article 20.
3. Marketing authorisation holders shall ensure continuous assessment and document the risk management measures and the outcome of risk minimisation measures in the pharmacovigilance system master file.
1. The signal management process shall consist of at least pharmacovigilance processes of signal detection, prioritisation, validation, assessment and documentation of outcome.
2. Where marketing authorisation holders are responsible for the same or a similar veterinary medicinal product as defined in the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) Guideline 24 ( 4 ) , authorised in different Member States through different authorisation procedures, the signal management process may be performed at active substance level for all the products combined.
3. Marketing authorisation holders shall perform signal management using a risk-based approach and monitor the data with a frequency proportionate to the identified risk. The risk-based approach shall take into account the following topics: type of product, length of time on the market and stability of the pharmacovigilance profile, identified and potential risks and the need for additional information. The risk-based approach shall be applied to determine the methodology, extent and frequency of the signal management process and the rationale shall be documented.
4. Signal assessment shall analyse and evaluate the potential impact of a signal on the benefit-risk balance of a product and shall allow for relative comparison between different products or product groups, including analysis at active substance level and stratified analyses.
5. The Agency shall publish guidance on best practice for signal management.
6. The outcome of the signal management process shall be recorded and the rationale shall be kept ready for inspection.
7. Marketing authorisation holders shall conduct at least one signal detection analysis per year for each of their active substances or products in the Union pharmacovigilance database.
8. Marketing authorisation holders using the Union pharmacovigilance database as their record management system for adverse event reports shall perform signal management in the Union pharmacovigilance database.
9. When marketing authorisation holders do not use the Union pharmacovigilance database for signal management, they shall ensure that their record management system for adverse event reports contain all adverse event reports for which they are responsible. In particular, they shall ensure that adverse event reports concerning their veterinary medicinal products reported to the Union pharmacovigilance database from other sources are recorded in their own database.
1. Marketing authorisation holders shall continuously monitor the benefit-risk balance of their products in light of all available information from veterinarians, other healthcare professionals, the general public, adverse event reports by other marketing authorisation holders or competent authorities recorded in the Union pharmacovigilance database, and scientific literature.
2. Marketing authorisation holders shall continuously monitor the benefit-risk balance and take necessary risk minimisation measures to optimise the safe use of their veterinary medicinal products.
3. Marketing authorisation holders shall consider the potential impact of each adverse event on the benefit-risk balance of their products, unless there is no causal link between their products and the adverse event.
1. Marketing authorisation holders shall annually record a conclusion on the benefit-risk balance for each of their products in the Union pharmacovigilance database and confirm that the signal management process has been conducted.
2. The outcome of the signal management process shall be included in the conclusion referred to in paragraph 1 if a new validated signal or signals related to medically important Veterinary Dictionary for Drug Regulatory Activities (VeDDRA) terms have been identified, even if no further action is considered necessary. The conclusion shall explain whether the benefit-risk balance is still considered as favourable and if any actions to improve the benefit-risk balance are deemed necessary.
3. When marketing authorisation holders identify a new risk or a change of the benefit-risk balance of one of their products, a summary of the analysis and a conclusion on the benefit-risk balance shall be recorded in the Union pharmacovigilance database. This shall be done in accordance with the timelines in Article 81(2) of Regulation (EU) 2019/6, notifying the competent authority or the Agency, as applicable.
1. Marketing authorisation holders shall have an overarching communication plan that identifies the relevant stakeholders in the Union, including veterinarians, other healthcare professionals, customers and the general public. In cases of urgent safety concerns, it shall outline the approach to be taken to communicate in a timely manner concerns arising from pharmacovigilance data or in relation to other relevant pharmacovigilance information.
2. The communication plan shall include information on how marketing authorisation holders:
(a)
identify the target audience;
(b)
identify effective means for communication with the intended target audience;
(c)
identify the specific objectives of the communication;
(d)
define a timetable for the communication;
(e)
ensure the relevance and clarity of the information for the intended target audience;
(f)
identify and coordinate all stakeholders involved in the communication;
(g)
give prior or simultaneous notification to the competent authority or the Agency, as applicable, of any public announcement on pharmacovigilance information, in accordance with Article 77(11) of Regulation (EU) 2019/6;
(h)
measure the effectiveness of the communication.
3. Marketing authorisation holders shall use the data-processing network of the Union pharmacovigilance database for communication of alerts related to pharmacovigilance data.
