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With the entry into force of the new Law of Ukraine “On Veterinary Medicine and Animal Welfare” No. 1206-IX of 4 February 2021, Ukraine is introducing a modern system of veterinary pharmacovigilance. The system provides for continuous monitoring of the safety and efficacy of veterinary medicinal products after they are placed on the market and involves marketing authorisation holders, veterinary practitioners and competent public authorities.

For Ukraine, this system is relatively new. In the European Union, however, pharmacovigilance has for many years been an integral part of the regulatory framework for veterinary medicinal products. The current EU system is based, in particular, on Regulation (EU) 2019/6 on veterinary medicinal products and the good pharmacovigilance practice requirements laid down in Implementing Regulation (EU) 2021/1281.

As Ukraine begins to develop its own pharmacovigilance practice, it is therefore important to understand how the system operates in the European Union, what role manufacturers and marketing authorisation holders play, what is expected from veterinary practitioners, and how an individual report of a suspected adverse event may ultimately affect the conditions of use of a veterinary medicinal product in the EU.

This article focuses specifically on the experience of the European Union.

What is pharmacovigilance?

The safety monitoring of a veterinary medicinal product does not end once the product has been authorised and placed on the market.

Even after all the required studies have been conducted, it is impossible to identify in advance every possible reaction that may occur when a product is used under real-life conditions – in different animal species and breeds, in animals with concurrent diseases, together with other medicines, or across very large animal populations.

This is why veterinary pharmacovigilance exists: a system for the continuous collection, analysis and assessment of information concerning the safety and efficacy of veterinary medicinal products after they have entered the market.

In the European Union, pharmacovigilance goes far beyond recording conventional adverse reactions. The system also covers information concerning adverse events in animals, lack of expected efficacy, adverse events in humans exposed to veterinary medicines, possible environmental effects, residue-related issues in food of animal origin, and suspected transmission of infectious agents through veterinary medicinal products.

Put simply, pharmacovigilance continuously seeks to answer two main questions:

Does the product remain safe and effective under real-world conditions, and has any new information emerged since its market entry that requires action?

Pharmacovigilance is a shared system

An effective pharmacovigilance system cannot be built by a public regulator or a pharmaceutical company alone. It operates as a chain in which every participant has a specific role.

A veterinary practitioner directly observes the animal and the outcome of treatment. A manufacturer or marketing authorisation holder collects information from different sources and analyses it at the level of the individual medicinal product. The competent authority, in turn, receives information from different companies and professionals and can assess developments across the wider market.

This means that even a single report from a veterinary practitioner can become part of a much larger picture.

For example, one veterinarian may report an unusual reaction following administration of a medicinal product. That individual case does not in itself prove that the medicine caused the reaction. However, if similar reports are received from different veterinarians, regions or countries, the pharmacovigilance system may identify a signal that requires further investigation.

Under EU rules, a signal is information arising from one or several sources that suggests a potentially new causal association, or a new aspect of a known association, between a medicinal product and an adverse event and which requires further investigation.

What is the role of veterinary pharmaceutical companies?

The primary responsibility for the continuous monitoring of a specific veterinary medicinal product lies with its marketing authorisation holder.

In the European Union, the marketing authorisation holder must establish and maintain a pharmacovigilance system capable of collecting, recording and evaluating information on suspected adverse events associated with its products.

This system includes quality management, risk management, continuous benefit-risk monitoring, signal management, and procedures for communication with regulatory authorities and other relevant stakeholders.

In other words, a company’s responsibility does not end when a marketing authorisation is granted.

The pharmacovigilance system must enable the company to receive information about events occurring in practice, analyse the data, compare it with other reports, and determine whether a new signal may be emerging.

In the EU, the marketing authorisation holder must also have a qualified person responsible for pharmacovigilance, while the overall pharmacovigilance system is described in a Pharmacovigilance System Master File – PSMF.

Pharmacovigilance for a pharmaceutical company is therefore not a one-off reporting obligation to the authorities. It is a continuous process of monitoring a medicinal product throughout its entire life on the market.

What is the role of the veterinary practitioner?

While the pharmaceutical company establishes and operates the pharmacovigilance system, veterinary practitioners are among the most important sources of information for that system.

Veterinarians are often the first to encounter situations where:

- an unusual or adverse reaction occurs;
- a medicinal product does not demonstrate the expected efficacy;
- a reaction appears more severe or different from what was expected;
- an adverse event occurs following use outside the authorised conditions;
- an adverse reaction occurs in a person exposed to the veterinary medicinal product;
- other circumstances arise that may indicate a safety or efficacy issue.

Importantly, the veterinary practitioner does not have to prove that the medicinal product caused the adverse event.

For pharmacovigilance purposes, a reasonable suspicion is sufficient. Assessing the causal relationship is subsequently the responsibility of the pharmacovigilance system, the marketing authorisation holder and, where necessary, the competent authority.

Why are reports from veterinary practitioners so important?

Clinical studies are conducted on a limited number of animals and under defined conditions. Once a medicinal product enters the market, however, it may be used in tens or hundreds of thousands of animals.

At that stage, rare reactions or patterns may become visible that could not have been identified during pre-authorisation studies.

A report of a suspected adverse reaction should therefore not be viewed as a statement that a product is “bad” or as automatic evidence of a quality problem.

It is data.

The purpose of pharmacovigilance is to collect enough of this data, analyse it and determine whether individual cases form part of a broader pattern.

What should be reported? Some practical examples

Pharmacovigilance is much broader than reporting a conventional adverse reaction to a medicinal product.

Below are several hypothetical examples.

Example 1. An adverse reaction following treatment

A veterinary practitioner prescribes a veterinary medicinal product for a dog in accordance with the approved product information. Several hours after administration, the animal develops symptoms that the veterinarian believes may potentially be associated with the medicine.

Even if the veterinarian cannot prove the causal relationship, the case is relevant to pharmacovigilance.

Example 2. A vaccine does not provide the expected protection

A poultry farm vaccinates its flock in accordance with the recommended vaccination schedule. Nevertheless, an outbreak subsequently occurs of the disease against which the vaccine was intended to provide protection.

This does not automatically mean that the vaccine was defective.

Possible explanations may include storage or transport conditions, the vaccination procedure, the health status of the animals, characteristics of the circulating pathogen, or other factors.

Nevertheless, suspected lack of expected efficacy is also pharmacovigilance information and should be recorded and assessed.

Example 3. An adverse reaction in a person

During administration of a veterinary medicinal product, a veterinarian or farm worker is accidentally exposed to the product – for example, through skin or eye contact or accidental self-injection.

The person subsequently develops an adverse reaction.

Such cases also fall within the scope of the EU veterinary pharmacovigilance system.

Example 4. Use outside the authorised conditions

A veterinarian uses a medicinal product in circumstances that differ from its authorised conditions – for example, in another animal species or at a different dosage – and an adverse event subsequently occurs.

Such a case may also be relevant for pharmacovigilance.

Example 5. Residue-related concerns

Following treatment of food-producing animals with a veterinary medicinal product, residues of a pharmacologically active substance are detected in food of animal origin above the established level, even though the required withdrawal period was respected.

EU legislation explicitly includes such cases within the scope of pharmacovigilance information.

Example 6. Potential environmental impact

Following use of a veterinary medicinal product, concerns arise about possible negative effects on the environment.

Such environmental incidents may also fall within the scope of EU veterinary pharmacovigilance.

Example 7. Suspected transmission of an infectious agent

If there is a suspicion that an infectious agent may have been transmitted through a veterinary medicinal product, this information must also be collected and assessed within the pharmacovigilance system.

The underlying principle in all these situations is the same: the veterinary practitioner reports a suspicion rather than establishing the final causal relationship.

How does the veterinary pharmacovigilance system work in the European Union?

The modern EU veterinary pharmacovigilance system is largely shaped by Regulation (EU) 2019/6 on veterinary medicinal products, which has applied since 28 January 2022.

Detailed rules on good pharmacovigilance practice are laid down, in particular, in Implementing Regulation (EU) 2021/1281.

In simplified terms, the system can be described as follows:

veterinarian / animal owner → report → company or competent authority → EU database → analysis → signal → risk assessment → regulatory action, where necessary.

1. A suspected adverse event occurs

The process often starts with an observation made by a veterinary practitioner.

The veterinarian observes an event following use of a veterinary medicinal product and considers that there may be a relationship between the product and the event.

A complete investigation or definitive proof of causality is not required before a report is submitted.

2. The information enters the pharmacovigilance system

Reports may be submitted to the marketing authorisation holder or to the competent authority.

Relevant data are then recorded in the Union Pharmacovigilance Database, the EU pharmacovigilance database established by the European Medicines Agency in cooperation with the Member States.

The database facilitates the exchange of pharmacovigilance data between Member States, EMA, the European Commission and marketing authorisation holders and makes it possible to use accumulated information for risk assessment.

Marketing authorisation holders are required to record received reports of suspected adverse events in the database within the prescribed timeframe – generally no later than 30 days after receiving the information.

As a result, reports from different countries do not remain isolated.

They can be analysed collectively, allowing patterns to be identified that might not be visible at the level of a single veterinary practitioner, company or even an individual country.

3. The company continuously analyses information about its products

The role of the marketing authorisation holder is not limited to entering individual reports into a database.

The company must continuously monitor the benefit-risk balance of its medicinal products using all available information, including reports from veterinarians and other professionals, data from competent authorities, information available in the Union Pharmacovigilance Database, scientific literature and other relevant sources.

This is an important distinction.

Modern EU pharmacovigilance is not simply about collecting reports. Companies must actively analyse the data and look for patterns.

4. The system looks for signals

Suppose one veterinarian reports an unusual reaction.

That is an individual case.

A similar report is then received from another country.

Later, several more comparable cases appear.

At this point, a signal may emerge — information suggesting a possible new risk or a new characteristic of an already known risk.

A signal, however, does not mean that causality has been proven.

This is why the process of signal management begins.

Under EU rules, signal management includes at least the following stages:

signal detection → prioritisation → validation → assessment → documentation of the outcome.

Signal detection

Reports and other available data are analysed to identify a potentially new issue.

Prioritisation

The potential seriousness of the signal is assessed, together with how urgently it needs to be evaluated.

Validation

The available information is reviewed to determine whether there is sufficient evidence for the signal to warrant further investigation.

Assessment

The possible causal relationship and the potential impact of the new information on the benefit-risk balance of the product are assessed in greater detail.

Decision

Following the assessment, the signal may be refuted, kept under further monitoring, or recognised as a new risk requiring action.

5. Signal analysis is a regular responsibility of the company

EU rules require marketing authorisation holders to perform at least one signal detection analysis per year for each relevant active substance or veterinary medicinal product in the Union Pharmacovigilance Database.

Monitoring must follow a risk-based approach. The frequency and depth of the analysis may depend on factors such as the type of product, how long it has been on the market, the stability of its safety profile and known or potential risks.

In addition, the marketing authorisation holder records an annual conclusion concerning the benefit-risk balance of the medicinal product and confirms that signal management activities have been performed.

6. What happens if a new risk is identified?

The purpose of pharmacovigilance is not to automatically prohibit a medicinal product whenever an adverse reaction is reported.

The key question is:

Has the benefit-risk balance of the medicinal product changed?

If, during signal management, the marketing authorisation holder identifies a new risk or a change in the benefit-risk balance, it must notify the competent authority or EMA without delay and no later than within 30 days, and take the necessary action.

Depending on the nature of the risk, possible measures may include:

- updating the product information;
- adding new warnings;
- revising contraindications;
- changing recommendations for use;
- introducing additional risk-minimisation measures;
- conducting additional monitoring or studies;
- modifying the terms of the marketing authorisation.

In exceptional circumstances, where the benefit-risk balance becomes unfavourable, regulators may take more substantial measures.

7. Who is responsible for the system at EU level?

Veterinary pharmacovigilance in the European Union is based on shared responsibility.

Veterinary practitioners and other professionals observe the effects of medicines under real-world conditions and are an important source of information on suspected adverse events.

Marketing authorisation holders establish pharmacovigilance systems, collect and analyse information, conduct signal management activities and continuously assess the benefit-risk balance of their products.

National competent authorities of the EU Member States perform oversight, analyse information and participate in regulatory decision-making.

The European Medicines Agency – EMA supports the EU-wide pharmacovigilance infrastructure and coordinates relevant activities at Union level.

The EU system can therefore be understood as a continuous cycle:

use of the medicinal product → observation → reporting → accumulation of data → analysis → signal detection → risk assessment → regulatory decision → safer use of the medicinal product.

The cycle then starts again.

This is why a report by a single veterinary practitioner, which may initially appear to be only an isolated clinical case, can potentially become part of a much broader system assessing the safety of a veterinary medicinal product across the entire European Union.

What does this mean for Ukraine?

The introduction of a veterinary pharmacovigilance system under the Law of Ukraine “On Veterinary Medicine and Animal Welfare” is an important element in aligning Ukraine’s regulatory framework for veterinary medicinal products with the European model.

However, establishing such a system is not merely a matter of adopting regulatory requirements.

Its effectiveness will largely depend on how understandable the system is for veterinary practitioners, how easy it is to report suspected adverse events, how effectively information is exchanged between companies and public authorities, and whether the Ukrainian model will in the future be able to interact efficiently with the EU pharmacovigilance system.

In our next article, we will take a closer look at how the pharmacovigilance system is organised in Ukraine, what obligations apply to veterinary practitioners and marketing authorisation holders, and how closely the current Ukrainian rules correspond to the European model.