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What this guidance covers

This guidance helps and encourages the reporting of problems with animal medicines, for the VMD to monitor their safety and effectiveness. This guidance is for animal owners, veterinary professionals, farmers and anyone else who uses or handles animal medicines.

It explains:

• what pharmacovigilance is, and why it matters
• how you can help by reporting a problem with a medicine
• what the VMD does with the reports it receives
• what actions the VMD can take
• what the VMD cannot help with

What the VMD cannot help with

Before reading further, it is worth knowing what falls outside the VMD’s role, as we receive many enquiries on these topics.

We do not give clinical advice. If you have concerns about an animal’s treatment or want advice on a specific medicine, contact the vet responsible for the animal’s care, or contact the pharmaceutical company responsible for the medicine (called the Marketing Authorisation Holder, or MAH). Their contact details can be found in the product packaging or on the VMD’s

We cannot deal with complaints about vets. If you have concerns about the conduct of a vet, including how they have treated an animal,

We do not comment on decisions made in other countries. Different countries follow their own regulations. The VMD can only make decisions about medicines authorised in the United Kingdom.

What is veterinary pharmacovigilance  

Veterinary pharmacovigilance is all about making sure that animal medicines continue to be safe and effective following their authorisation for use. No medicine is risk free, with adverse events identified during assessment and noted on the product packaging. Risks can be further reduced by post surveillance monitoring and taking action to prevent problems that might arise.

The has defined pharmacovigilance as the science and  activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem. This principle also applies to veterinary medicinal products.

This means that pharmacovigilance involves:

• monitoring the everyday use of medicines in the real world to identify problems, reactions or side effects (known as ‘adverse events’)
• analysing and assessing the benefits and risks of a medicine
• taking actions where needed to ensure the benefits of the medicine outweigh the risks
• monitoring the impact of these actions.

The VMD is responsible for veterinary pharmacovigilance in Great Britain.

Pharmaceutical companies (MAHs) are legally required to monitor the safety of their own medicines and report to us. Veterinary professionals, animal owners, farmers and others contribute by reporting problems they observe.

Why is pharmacovigilance important

When a veterinary medicine is first approved, the VMD makes an assessment using all available evidence. As the medicine has not yet been on the market, only data from clinical trials or from similar products is available. This means at the time of approval the product has often only been tested in a relatively small number of animals for a limited length of time. Therefore, post-marketing data and pharmacovigilance is essential in assuring the long-term safety and effectiveness of medicines.

Detailed information on what MAHs must do to apply for approval of a medicine can be found in Marketing authorisations for veterinary medicines - °Ç¸ç³Ô¹Ï.

At the time of approval, known adverse events are included in the product information, on the Summary of Product Characteristics (SPC) and the package labelling or leaflet which accompany the medicine.

Once a medicine is on the market, a much larger population of animals, and humans are exposed to the product compared to the number in clinical trials. Sometimes, adverse events that were not identified during the clinical trial are identified post-marketing. This is especially the case for rare or very rare adverse events or adverse events that take some time to develop.

Additionally, more information can also be gathered on known adverse events and particular risk factors such as age, breed, underlying disease and genetic predisposition that might make an animal more likely to experience an adverse event. To put this in context, at least 30,000 animals need to be treated with an animal medicine to be sure that you do not miss at least one patient with an adverse event which has an incidence of 1 in 10,000 exposed animals; described as a very rare event.

Further data can also be gathered as to whether the medicines are working as expected in a larger population.

Pharmacovigilance looks at a much larger amount of information than initial assessment data, which builds over time as more becomes known about the product.

For an animal medicine to be considered safe, its expected benefits should be greater than any associated risks of harmful reactions.

Medicines are needed to ensure the welfare of animals, but any medicine can cause reactions. However, most animals are administered medicines without suffering any serious side effects.

It is important that users of the medicine, in particular veterinary professionals, but also animal owners, are made aware of the risks so that they can make an informed decision regarding the use of the medicine in animals under their care.

Veterinary professionals should be able to discuss such information with animal owners, be vigilant in the detection of suspected adverse events and prompt in reporting them to marketing authorisation holders or the VMD.

Who is responsible for pharmacovigilance in the UK

In the United Kingdom, the VMD is the government body responsible for overseeing veterinary pharmacovigilance. They make sure that pharmaceutical companies responsible for animal medicines (MAHs) are actively monitoring their safety and effectiveness.

• MAHs are legally required to monitor and report adverse event data.
• VMD oversees the process, does their own analysis and makes regulatory decisions.
• Public and professionals (veterinary professionals, farmers, pet owners) contribute by reporting adverse events.

The VMD inspects MAHs to ensure that they have the personnel, systems, and facilities in place to comply with their pharmacovigilance obligations. Further information on the scope of inspections can be found at pharmacovigilance compliance and inspections.

Animal medicines authorised for use in Northern Ireland under the Windsor Framework are subject to EU legislation and pharmacovigilance requirements. The VMD is still responsible for the oversight of veterinary pharmacovigilance for animal medicines on the Northern Irish market, and enforcement of the relevant EU legislation and requirements.

What is an adverse event

Adverse effects, or adverse events as they are more widely described in veterinary pharmacovigilance, are observations that are unfavourable and unintended that happen after giving a medicine to an animal or after an animal or human are exposed to a medicine.

Adverse events might include:

• an unexpected side effect such as vomiting or a skin reaction
• a medicine not working as well as expected (known as a suspected lack of efficacy)
• a risk to a person handling a medicine
• an environmental impact, for example, contamination

Adverse events can occur following:

• use of a medicine intended to treat an animal
• off-label use of a medicine (using in a way not specified on the label – for example, under the prescribing cascade)
• use of an unauthorised product
• use of extemporaneous preparations (or ‘specials’)
• accidental or intentional exposure of an animal to a human or veterinary medicines (whether authorised for use in the UK or not)
• use of any other medicine to which an animal has been exposed accidentally or otherwise, and the animal has been adversely affected

If you are unsure whether what you observed counts as an adverse event, it is better to report anyway. We would rather receive a report that turns out not to be related to the medicine than miss something important .

Once a product is first marketed, it is monitored for the rest of its time on the market so we can assure it remains safe and effective.

What is a ‘serious’ adverse event

Adverse event reports are sometimes categorised by seriousness, to aid in prioritisation of assessment.

In pharmacovigilance, a serious adverse event is one which that:

• results in death
• is life-threatening
• results in persistent or significant disability/incapacity
• cause a congenital anomaly or birth defect

For animals managed and treated as a group, such as a herd or flock, a serious adverse event is an increased rate of serious adverse events exceeding the rates normally expected in that particular group.

It is important to note we take all reports of adverse events seriously, regardless of classification. When we assess adverse events, an adverse event report that is individually categorised as serious is not necessarily prioritised above one that is categorised as non-serious. When we perform an in-depth assessment, we look at all reports involving the event in question, whether those reports have been categorised as serious or not.

What is a suspected lack of efficacy

Where a product is not working as expected, this is known as lack of efficacy. It is very important to monitor lack of efficacy, as it may mean that the benefits of the medicine no longer outweigh its risks as it is not having the required effect. It may mean that changes need to be made in the way the product is used. This information may also be used to drive development of new, more effective products.

Who can report an adverse event

Anyone can report an adverse event. You do not need to be a vet or have specialist knowledge. This includes:

• vets and vet nurses
• Suitably Qualified Persons (SQPs)
• pet owners, farmers and animal keepers 
• anyone who accidentally comes into contact with an animal medicine

The current Veterinary Medicines Regulations do not require veterinary professionals to report adverse events. The Royal College of Veterinary Surgeons has a which describes how vets have a moral and professional obligation to report any observations after the use of veterinary medicinal products to the MAH. Vets must also be up to date with the safety profile of the products they prescribe and administer and discuss that information with the animal owner.

How do I report an adverse event

For most authorised veterinary medicines, you can report to either:

• the MAH (the pharmaceutical company responsible for the medicine), or
• the VMD directly

You do not need to report to both the MAH and VMD. Doing so may result in duplicate reporting, which can slow down our work and affect the evidence we base decisions on.

MAHs have a legal obligation to report all adverse event reports they receive to the VMD within 30 days of awareness.

For help on using the VMD’s online reporting form please visit our detailed guide ‘How to report a problem with an animal medicine online’ [LINK]

Northern Ireland

Northern Ireland authorisations fall under European Union legislation:

How can I create a high-quality report

The reporting of adverse events is critical to increasing the volume of data available for ongoing monitoring to protect animal health, public health and the environment. The VMD makes decisions based upon the evidence available to it, so providing a high-quality report is essential to build evidence. 

When reporting provide as much information as possible about the:

• animal(s) affected
• human(s) affected
• product(s) administered
• event(s) that occurred

For specific details on what to include within your report to make it as useful as possible visit our guidance on ’How to report a problem with an animal medicine online’

Occasionally, it may be necessary to obtain further information or clarification from the reporter, so that the report can be properly evaluated.

Adverse event reports received to the VMD

The VMD currently receives around 25,000 adverse event reports a year and monitors over 6,000 authorised veterinary medicinal products (VMPs).

All reports enter our database and are evaluated.

We constantly review adverse event report data to ensure that the overall benefits of each product approved in the United Kingdom outweigh the risks posed by their potential adverse events.

What happens to an adverse event report when it is received by the VMD

Step 1: Validation

When an adverse event report is received by the VMD, it enters our main pharmacovigilance database.

We first validate all reports received directly to the VMD, by confirming that they include: an identifiable reporter, an identifiable patient, one or more products and one or more adverse events that occurred following administration of the product(s).

We check that the information provided is not duplicate information, for example if the report has been submitted to both the VMD and the MAH.

We check the information in the report is reflected in our database and we write a short summary of the report, known as a ‘narrative’. We also code the events reported using the This is a standardised list used by many countries to translate descriptions of events into data that can be analysed. Once anonymised, we share information  with the MAH so that both the VMD and the company can monitor the product(s) effectively.

Step 2: Analysis

All reports in our main pharmacovigilance database are included within a monthly analysis. We run calculations to statistically analyse the data. These highlight changes in the data and allows us to identify products and events that differ from or appear to be forming a pattern against background data.

We prioritise results based on risk. Higher risks  include those which involve the most medically important events or where there have been many adverse event reports received. We then investigate the product-event pairs to see whether it is likely that the event is caused by the product. Where there are many adverse event cases, or we want to further investigate a particular area, we may perform an additional more in-depth analysis of the data.

Step 3: Assessment

The results of our analysis are then reviewed at monthly Signal Detection meetings and subsequently with other teams at the VMD at regular Benefit-Risk meetings. This allows us to assess the most appropriate course of action.

At this stage, actions may be taken, or we may determine that there is insufficient or inadequate quality data make a decision as to whether corrective actions are required. We may then ask the MAH to closely monitor the product, which involves more regular and in-depth analysis than usual, or we may similarly monitor the product, independently. We routinely monitor new products more regularly, which include new ingredients that have never or rarely been used in veterinary medicine.

The pharmacovigilance activities are presented at the quarterly Veterinary Products Committee (VPC). This VPC is a scientific non-departmental public body sponsored by the Department for Environment, Food & Rural Affairs to provide advice on veterinary medicinal products and animal feed additives.   

How do we assess pharmacovigilance data

Assessment of pharmacovigilance data is a highly complex process which is undertaken by veterinary surgeons alongside toxicologists and scientists at the VMD, who have expertise in assessing the benefits and risks of medicines. This assessment involves both quantitative (statistical) and qualitative methods.

The fact that adverse events have occurred following administration of a product, does not necessarily mean that those adverse events were caused by the product. For example:

• there may have been multiple products administered and the adverse events may have been caused by only one product
• the animal may have, for example, eaten a poisonous food or had an accident around the time the product was administered, and the signs seen may be more likely to be caused by the poisoning or accident
• the product may have been used incorrectly or as directed by the veterinarian, outside of the recommendations on the label

The following list contains some of the factors considered during assessment:

• total number of cases (excluding duplicates)
• whether reports are increasing (incidence)
• clinical relevance (seriousness, severity, outcome, reversibility, relationship to features of the patient, such as, species, age)
• dose-adverse event relationship
• interactions with other medicines
• the consistency between reports (timing, pattern of events, outcome, dosages involved)
• plausibility of a pharmacological or biological explanation linking the product and event, or a lack of alternative causes
• whether the event goes away when product administration is stopped and/or returns when administration is restarted
• supportive relevant investigation or laboratory findings
• clinically similar events occurring in additional reports
• other potentially impacting clinical variables such as concurrently administered products, medical history
• potential for over-reporting, for example due to increased media attention, or a known increase in sales volumes

We always consider the likelihood of underreporting when assessing any concerns, however decisions made are made on the evidence available.

The VMD’s pharmacovigilance team assists with the assessment of initial authorisations (approvals) and post-approval updates to the product information.   

What is signal detection

A signal is information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. Signals are generated from several sources such as spontaneous adverse event reports, clinical studies and the scientific literature.

The presence of a safety signal does not directly mean that a medicine has caused the reported adverse event. An illness or another medicine administered to the patient could also be the cause. The assessment of safety signals aims to establish whether there is a causal relationship between the medicine and the reported adverse event.  

MAHs must perform continuous signal detection. The VMD independently reviews or assesses the content of these signal notifications alongside data in our database, and we either agree or disagree with the proposal. Where the MAH wishes to update the information that accompanies the product, they will apply to do so, and this may then be assessed via a specific pathway.

Where we disagree with a proposal, we will request an alternative action is performed.

What actions we might take and when

We consider many factors when deciding whether to take actions related to a medicine’s safety. Therefore, there is no specific threshold for regulatory actions to be triggered.

Potential actions that may be taken include:

• updating the product information, for example, by listing additional adverse events on the label so that veterinary professionals and animal owners are aware of these risks
• requiring that MAHs issue important safety information to veterinary professionals and animal owners. The VMD will also issue similar communications
• conducting close monitoring if there is not yet enough information to determine whether there is a link between the product and the event
• commissioning a post-marketing study to try and build more evidence to support a decision
• suspension or withdrawal of the product. This would happen if the overall risks outweighed the benefits of the product (or a particular batch) and proposed risk minimisation measures were considered inadequate

Changes to product information are published on the VMD’s . We also publish urgent safety updates and, for products of particular significance, detailed assessment findings.

We would not add every reported event to a product’s information without first assessing whether the medicine is likely to have caused it. Adding unverified events to product labels would make it harder for veterinary professionals and animal owners to make informed decisions about treatment and could harm animal welfare.

There may be differences in the decisions made by and data that appears on product information in different jurisdictions. Each jurisdiction follows specific legislation and guidelines, which regulate the safety information to be included on the veterinary medicine label and information leaflet during the authorisation process and the procedures to change this label as necessary, once the medicine is placed on the market and following analysis of post-marketing pharmacovigilance data. The (Veterinary Medicines Regulations 2013) is similar to that of comparative European countries. The VMD cannot comment on the actions of other jurisdictions.

Where does pharmacovigilance data come from

The most important source of data is adverse event reports submitted by veterinary professionals, animal owners, farmers and others. These provide real-world evidence that is essential to our work. This is why we strongly encourage everyone to report.

We also use:

• post-marketing research studies
• data collected from veterinary or other databases such as veterinary practice systems or those held by other government organisations
• reports of product defects
• published scientific literature
• data from other regulatory agencies

Data from pharmaceutical companies

Marketing Authorisation Holders (pharmaceutical companies or MAHs) are legally required to continuously monitor the safety of their medicines.

In the UK, before submitting a request to obtain a marketing authorisation (gain approval) for a new product, MAHs must describe the pharmacovigilance system they have or will have in place to monitor that product.

Once a medicine is approved, MAHs are legally required to:

• collect adverse event reports and send them to the VMD within 30 days of becoming aware of them
• send signals which suggests a new risk or a change in the benefit-risk balance of the product to the VMD within 30 days
• send urgent signals, which are ones that require rapid implementation of risk minimisation/safety measures, to the VMD within 1-3 days
• submit a Benefit-Risk Report at least annually, including an assessment of whether the medicine’s benefits still outweigh its risks
• provide annual data on sales volumes and estimated use by species, so that the VMD can put the number of adverse event reports in context

We provide MAHs with detailed guidance on how to perform pharmacovigilance to the required standard, this guidance is available in: Pharmacovigilance of Veterinary Medicinal Products in Great Britain - °Ç¸ç³Ô¹Ï. We inspect MAHs to check they are meeting their legal obligations as set out in , and monitor this as part of our routine pharmacovigilance activities.

Data considerations  

The VMD processes large volumes of data for pharmacovigilance.

Some data, such as a sales data, is provided to us by the MAH and therefore cannot be independently verified in full, though our inspections and compliance activities help ensure accuracy

Evaluation of adverse event reports is dependent on the accuracy and quality of data received from veterinary professionals and animal owners. Rates of reporting can vary over time, for example when a product is newly launch or receives significant social media and press interest. We take these factors into account when assessing the data.

What other activities does the VMD Pharmacovigilance team perform

Inspections

We inspect Marketing Authorisation Holders to ensure that they have the personnel, systems, and facilities in place to comply with their pharmacovigilance obligations as described in the VMR Schedule 1 Part 8 paragraph 60A. Any Marketing Authorisation Holder with a product authorised in GB can be subject to a pharmacovigilance inspection by the VMD, which may also include any of their partners or service providers.

Further information on the scope of inspections can be found at pharmacovigilance compliance and inspections.

Communication

We perform a number of communication activities including

• updating the product literature with new safety warnings
• publishing urgent and clinically significant safety updates on gov.uk
• contributing to the publication of a of product information changes
• publishing news stories and in-depth assessment findings for products or ingredients of particular importance
• answering Freedom of Information requests and enquiries from animal owners, veterinary professionals and scientists, among others

International activities

• Collaboration with other regulators across the world
• Active participation in international groups such as (EU-Japan-USA programme aimed at harmonising technical veterinary product registration and monitoring requirements) and the , and attending pharmacovigilance conferences
• Providing training for regulatory agencies in other countries

Other activities

• Assessing pharmacovigilance data related to product defects
• Sharing data as required for use in activities performed by other teams within the VMD or within other government organisations
• Answering queries from MAHs and providing training to ensure that they can adequately comply with the law and guidance
• Continuous data cleansing and review to ensure the data we are basing our decisions on is as accurate as possible
• Continuous improvement of our systems and processes to ensure they are working as effectively and efficiently as they can
• Internal training, including pharmacovigilance, civil service and, for those veterinary surgeons in the team, veterinary professional development

Data and privacy

We want you to understand how we use the information you give us when you submit an adverse event report. Your privacy is important to us, and we handle all personal data in line with UK data protection law.

For full details, please read our Privacy notice.