Guidance

Adverse event reporting

Updated 8 June 2022

Applies to England, Scotland and Wales

1. Introduction

The obligations of the Marketing Authorisation Holder (MAH) for recording and reporting adverse events associated with their veterinary medicines for which Marketing Authorisations (MAs) are held are defined in the VMR 2013 Schedule 1 Part 8 paragraph 57-59.

The term adverse event used in this guidance is as defined in VICH GL24: any observation in animals, whether or not considered to be product-related, that is unfavourable and unintended and that occurs after any use of a veterinary medicine, off-label and on-label uses. Included are events related to a suspected lack of expected efficacy according to approved labelling or noxious reactions in humans after being exposed to a veterinary medicine.

For authorised veterinary medicines, independent of the authorisation procedure, adverse events received from veterinarians, other health-care professionals and other sources should be reported, regardless of whether or not the product was used in accordance with the authorised SPC and/or any other conditions laid down for marketing of the product in accordance with applicable legal requirements. Adverse events identified from the worldwide-published peer reviewed scientific literature should also be reported.

Electronic reporting of adverse events is mandatory, save in exceptional circumstances.

The MAH is expected to validate all adverse events reported by veterinarians, other health-care professionals and the general public to ensure, prior to reporting to the VMD, that the minimum information required is included in the report. Reports should be followed-up to obtain additional information relevant to the case as necessary, and relevant follow-up information should be reported to the VMD. All available information relevant to the evaluation of the adverse event should be provided.

2. Requirements for expedited reporting

For all veterinary medicines, independent of the authorisation procedure, the MAH should report, on an expedited basis, all serious adverse events, human adverse reactions and unintended transmission of an infectious agent through a veterinary medicine occurring in the UK to the VMD.

All other adverse event reports may also be submitted to the VMD if MAHs would wish to use the same reporting systems as they will use for their EU MAs. In this case, adverse reports not qualifying as serious, human or unintended transmission of an infectious agent, are expected to be submitted within 30 days of the MAH becoming aware of them.

In veterinary medicine the diversity of animal species and husbandry conditions require a modified approach to the classification of a serious adverse event. For example, in intensive food animal production with species such as poultry, fish or bees, a certain level of mortality rate is considered as ‘normal’ or ‘expected’. These species are usually treated as a group/flock and only an increase of mortality rate, or severe signs, or animal production losses exceeding the rates normally expected should be considered as a serious adverse event. However, for food producing animals treated on an individual basis, an individual death or severe symptoms should be regarded as a serious adverse event. Similarly, for companion animal species, like dogs and cats, a single death or severe symptoms constitutes a serious adverse event.

2.1 Reporting of serious adverse events including human adverse reactions occurring in the UK

The MAH should record and report all serious adverse events in animals and all human reactions occurring in the UK which are brought to their attention, or of which they can reasonably be expected to have knowledge. These reports should be reported promptly, and no later than 15 calendar days from receipt, to the VMD. Receipt in this context means the MAH becoming aware of an adverse event. A serious adverse event is any adverse event which results in death, is life-threatening, results in persistent or significant disability/incapacity, or a congenital anomaly or birth defect as defined in VICH GL24. For animals managed as a group only an increased incidence of serious adverse events as defined above exceeding the rates normally expected in that particular group is considered a serious adverse event.

It should be noted that serious adverse events together with all other pharmacovigilance issues should also be included in the analysis of the benefit:risk balance in a Periodic Safety Update Report (PSUR).

Some marketing authorisation holders have distributors and/or other MAHs/entities with whom they have agreements regarding pharmacovigilance activities. In this situation MAHs should ensure that detailed and clear documented contractual agreements describing roles and responsibilities for meeting pharmacovigilance obligations are in place between MAHs and other persons or organisations involved in the fulfilment of pharmacovigilance obligations, including where appropriate the immediate transfer of adverse event reports and pharmacovigilance information to the ‘parent’ MAH. In cases of these agreements day 0 is considered the day that the distributor/other entity became aware of the adverse event.

2.2 Reporting of serious and unexpected adverse events, including human adverse reactions, and transmission of infectious agents occurring outside the UK

The MAH should keep a record of all adverse events in animals, all human adverse reactions and any suspected transmission of an infectious agent relating to the use of a veterinary medicine which have occurred outside the UK; that is non-UK reports, and which are brought to their attention or of which they can reasonably be expected to have knowledge. These should be not be routinely submitted to the VMD. The VMD may request these cases from a MAH on a case-by-case basis. Details of their submission and timelines will be provided at that time.

It should be noted that all adverse events occurring outside the UK should also be considered in the analysis in a Periodic Safety Update Report.

Where veterinary medicines are authorised under different names in non-UK reports to enable analysis of pharmacovigilance data, the MAH should identify the same or similar products and provide the corresponding product names and authorisation numbers to the VMD if requested to do so. The terms same or similar Veterinary Medicinal Product (VMP) are defined in VICH GL24.

English language shall be used for the reporting of all adverse events including those originating outside the UK.

2.3 Requirements for expedited reporting

Marketing Authorisation type	Source	Origin	Adverse event type	Target	Timeline
All authorised products in the UK	Any source	UK	All serious adverse events in animals, all human adverse reactions and any suspected transmission via a veterinary medicine of an infectious agent	To VMD	Within 15 days

2.4 Reporting of lack of expected efficacy

Lack of expected efficacy (LEE) is defined as the apparent inability of an authorised veterinary medicine to have the expected efficacy in an animal, according to the claims of the SPC and following use of the product in accordance with the SPC. It is important to identify if this is due to a possible batch quality problem. When such a problem is identified, this and any other product defect related issues must be reported to the VMD.

All reports of LEE, regardless of whether or not the product was used in accordance with the SPC, should be recorded by the person responsible for pharmacovigilance and reported to the VMD in the same way as for other adverse event reports.

The VICH definition of an adverse event includes LEE, therefore it follows that LEE reports which result in death, are life-threatening, or which result in persistent or significant disability/incapacity, or congenital anomalies or birth defects should be expedited to the VMD within 15 days.

If a case includes a LEE report then this should be VeDDRA coded with an appropriate LEE VeDDRA low level term, with a relevant death VeDDRA low level term added if required. No other clinical signs relating to the LEE should be coded using VeDDRA. In LEE reports following use of euthanasia products, these events should be coded using only the VeDDRA low level terms ‘lack of efficacy-NOS’ and ‘unrelated death’; as death was unrelated to the adverse event ‘lack of efficacy’. Such reports are considered serious adverse events and should be reported accordingly.

2.5 Reporting of adverse events following off-label use

Off-label use relates to situations where the veterinary medicinal product is used outside the terms of the marketing authorisation.

The MAH should collect any available information on adverse events following off-label use related to his veterinary medicines. Reports of adverse events arising from off-label use should be routinely followed up to ensure that information is as complete as possible regarding the clinical signs, treatment and outcome.

Reports of adverse events arising from off-label use may be obtained:

• after use of veterinary medicines outside the terms of the MA, for example use of a product in non-authorised species or for an unauthorised indication or use at doses differing from those set out in the SPC and package leaflet
• after use of veterinary medicines under the provisions of the Cascade

Such reports can provide useful information on the safety of the veterinary medicine and should be recorded by the person responsible for pharmacovigilance and reported to the VMD in the same way as other adverse events. For some products the ‘Target Species’ section of the Summary of Product Characteristics (SPC) indicates a given target species, and in other sections of the same SPC, such as indications, contraindications, special precautions for use, there is a restriction of use within this target species, for example restriction to a category of age, weight, physiological status, type of production etc.

Adverse events in animals belonging to the target species, but not the subgroup of animals to which use is restricted within the target species, should be considered as off label use in the target species. Consequently, the explanation for the “Use according to label” should mention “No” and the explanation should include “Unauthorised species/species subgroup”.

For a case where the product was prescribed by a veterinarian, but on purpose not according to label, the adverse event should be reported as ‘off label’ for the specific veterinary medicine.

If there were mistakes in prescribing, storing, the preparation or the administration of a product, the event should be reported as ‘off label’ for the specific veterinary medicinal product and the VeDDRA low level term ‘medication error’ added to the report.

3. Requirements for reporting other pharmacovigilance issues

3.1 Reporting on investigation of the validity of the withdrawal period

Reports of such cases may arise from different sources including:

• farmers or veterinarians detecting residues of veterinary medicines when testing bulk milk for antibiotics
• analytical laboratories or food producers who routinely monitor foodstuffs for residues, for example in slaughterhouses or dairies
• state or regional authorities conducting residue surveillance on food from food producing animals

Where levels of veterinary medicine residues in tissues or food products of treated food producing animals are above the established maximum residue levels while the recommended withdrawal period of the given medicine has been respected, this information may cast doubt on the validity of the withdrawal period and consequently should be investigated and reported to the VMD. If the case meets the minimum information required for adverse event reports, then it should be recorded and reported even if the information about whether the recommended withdrawal period has been respected is unknown.

In circumstances where these reports cast important doubt on the appropriateness of the recommended withdrawal period of the given veterinary medicine, the reports should be recorded and may be reported within 30 days after receipt to the VMD.

The report should contain details about:

• the source of the report
• the veterinary medicine, including active ingredients
• MA number and batch number if available
• the route of administration
• the withdrawal period applied
• date of use
• date of detection of the residues
• the level of residues detected
• the location of the case
• the species
• the analytical method used to determine the residues
• any other information necessary for a detailed evaluation of the case
• the steps taken by the MAH to investigate the matter

3.2 Reporting on environmental incidents

A potential environmental incident is a situation where an ecosystem is adversely affected through exposure to a veterinary medicinal product. Such incidents may involve animals of non-target species or presence of active substances in soil or water at levels considered harmful for the ecosystem affected.

Any suspected environmental incident related to veterinary medicine exposure should be recorded by the MAH as soon as it comes to his knowledge.

The minimum requirements for any potential environmental incident to be recorded by the MAH and reported to the VMD are:

• the location
• the ecosystem, animal or plant involved, as appropriate
• the nature of the suspected environmental incident
• the suspected products

Reports of potential environmental incidents arising from the use of a veterinary medicine may be submitted to the VMD within 30 days after receipt and should be evaluated in the relevant PSUR.

4. Guidance on particular types of reports

4.1 Adverse events involving more than one species

If more than one species is involved in the same adverse event, separate reports should be submitted for each species, although it should be indicated that the reports are linked. This applies when more than one animal species is involved, or when an animal and a human being are involved.

4.2 Adverse events involving an untreated animal exposed to a veterinary medicine via a treated animal

If an adverse event has occurred in an untreated animal exposed to a treated animal, even if of a different species, a single report should be submitted relating only to the animal which experienced the adverse event. In this case a short explanation should be included in the dose details to clearly indicate which animal, or animal species, was treated. In addition, the administration route details should reflect the route by which the affected animal was exposed, such as oral route if the contact was by licking or grooming, cutaneous route if there was dermal contact between the treated and untreated animal.

4.3 Adverse events in offspring exposed through a parent

Abortion

Abortion: A report should be submitted relating to the parent. The animal details should be those of the mother. The number recorded should relate to the parent. The number of aborted animals should only be stated in the case narrative and should not be counted as number of animals died.

Stillbirth

A report should be submitted relating to the parent. The animal details should be those of the mother. The number of stillbirth offspring should be counted as the number of animals died.

Adverse events in offspring only

The number of animals treated should be the parent. The number of animals affected should be recorded in the relevant mandatory field.

If appropriate, record the number of offspring in the litter which reacted. A short explanation should be included in the narrative to indicate which parent was treated.

Adverse events in parent and offspring

In cases where the parent and offspring experienced one or more adverse events following the administration of a veterinary medicine to the parent during pregnancy resulting in in utero exposure of the foetus/foetuses, or during lactation, a single report should be submitted relating to both parent and offspring. The animal details to be recorded should be those of the parent. The number of parent and offspring affected should be recorded in the relevant mandatory field and the fact that their exposure occurred in utero if appropriate, should be recorded in the case narrative. The clinical terms used to describe the adverse event should include the clinical signs observed in the offspring as well as those experienced by the parent. If the parent or any offspring died, the report should be sent as an expedited report.

5. Required information for adverse event reports

5.1 Minimum information for adverse event reports

For a recordable case MAHs are expected to record all data relevant for the evaluation and provided by the sender or obtained in the context of the case, and at least the minimum criteria. If relevant for the evaluation, the MAH is expected to follow-up the adverse event with reasonable effort, to obtain further pertinent information. It is essential for MAHs to provide details as completely as possible, including all relevant clinical information and results of appropriate diagnostic tests, in order to facilitate assessment. The original words and/or phrases used by the reporter should be provided even if they are also coded using the VeDDRA List of Clinical Terms for reporting adverse events in animals and humans.

The use of internationally agreed standard terminology lists is a crucial factor in harmonising the exchange of pharmacovigilance information, and VeDDRA terminology is the most important of the standard lists. It is required that the MAH shall use VeDDRA terminology and the latest version should be used in line with specified implementation dates if possible. The VeDDRA lists are revised regularly and are available on the EMA website.

Follow-up reports to incomplete adverse event reports should be submitted by the MAH to VMD, in particular in cases where only the minimum information was submitted initially or when the investigation of the adverse event is completed.

A report will be considered an acceptable and reportable adverse event report provided that at least the minimum information outlined below is available. These details should be recorded by the MAH for any adverse event, whether non-serious or serious, whether occurring in animals or in human beings, whether occurring in the UK or outside the UK, and must be reported to the VMD as appropriate.

Minimum information for adverse event reports:

• an identifiable source or primary reporter. Wherever possible this should include the name and address of the primary reporter. Initials, geographic location or other unique identifier should be provided to allow the collection of further information and to avoid any duplication of reports whilst fully complying with relevant data protection laws, for example the General Data Protection Regulation (GDPR) and privacy legislation
• animal details: Species, sex, age or Patient details: Sex, age or adult/child. For both animal and human reports, it should be stated if sex and/or age are not known
• veterinary medicine concerned: name and marketing authorisation number
• it is recommended to record in the case narrative the opinion of the primary reporter and attending veterinarian identifying which products or active substances are considered suspected where available
• adverse event details

Electronic reporting has additional data fields marked as mandatory.

Additional criteria to enable electronic reporting:

• Unique Adverse Event Report Identification Number (AERID)
• receiver identifier
• date of the reaction. If this is not known, the closest approximation in terms of year and month if known should be substituted
• the number exposed/affected. If the number exposed is not known, the number affected should be substituted. If neither the numbers exposed nor affected are known, a notional figure should be used, which should be justified. If the exact numbers of animals exposed are not known, an estimation should always be provided. It is not acceptable to omit this information

These details allow for the management and electronic distribution of adverse event reports and assist in the detection of duplicate reports.

For adverse events for which deadlines for reporting apply, the reference point for deadlines for submission of reports is the time of receipt of the minimum information.

It should be emphasised that these are minimum requirements and the MAH should try to include as much information as possible, described below in order to facilitate a full evaluation.

MAH details and original reporter’s details:

• the name of the sender employed by the MAH
• address, telephone and fax number of the sender
• MAH report reference number
• date of receipt of report by MAH: applies to any personnel of the MAH or an organisation having a contractual arrangement with the MAH
• source of report, for example, spontaneous, post-authorisation safety studies, literature report or clinical studies • details of the original reporter - initials, first 2 digits of postcode, profession and speciality, if available • reporting country: country where the incident occurred • purchase country: where suspect product was purchased if different from that above

Animal Details:

• number exposed
• characteristics of animals showing signs:
• species
• breed
• sex
• age in days/weeks/months/years
• weight in kilograms

Suspect veterinary medicine details:

• product names/brand names
• approved scientific names: INN - International Non-proprietary Name
• marketing authorisation number
• ATCvet code
• pharmaceutical form
• batch number
• expiry date of batch - if relevant
• storage details - if relevant

Administration details:

• the person who administered the veterinary medicine, for example, animal owner, veterinary surgeon
• reason for use of the product, including diagnosis
• dose, and frequency, if relevant, of product given
• route of administration
• start date
• stop date and/or duration
• time between administration and adverse event
• action taken after adverse event, for example withdrawal of product, dose reduction
• previous adverse events to the veterinary medicine if occurred/reported; re-challenge information to include:
  • approximate date when animals were previously administered the product
  • description of adverse events
  • outcome including any treatment given

5.2 Other products used concurrently

All medicinal products preceding the adverse event should be provided when available. This should also include non-prescription medicines, extemporaneous preparations and medicated feeding stuffs if applicable. In the case of extemporaneous preparations, details of individual constituents of the formula should be indicated.

For each medication:

• product name/brand name: where a specific veterinary medicine cannot be identified, the names of the active substances should be reported
• approved scientific names: INN - International Non-proprietary Name
• MA number
• ATCvet code
• pharmaceutical form
• batch number if relevant
• expiry date of batch - if relevant
• storage details - if relevant

Administration details for other products used concurrently:

• the person who administered the veterinary medicine: for example animal owner, veterinary surgeon
• dose, and frequency if relevant, of product given
• route of administration
• start date
• stop date and/or duration
• other relevant information

5.3 Details of the animal adverse event

The case narrative is very important and should contain all known relevant clinical and related information, including animal, exposure or treatment details not otherwise reported, course of adverse event and description of the adverse event including the outcome, diagnosis, and any other information that supports or negates an association between a product and an adverse event. The narrative should serve as a complete and comprehensive case report, presented in a logical time sequence, in chronological order. The use of abbreviations and acronyms should be avoided:

• description of adverse event including site and severity, or intensity, of the adverse event, and clinical signs
• start date or onset of adverse event
• stop date or duration of adverse event
• specific treatments adopted against the observed adverse event
• number of animals showing signs
• number of animals that died or were euthanised
• de-challenge information; such as any obvious effect of removal of the product
• if available, the following information should be provided:
  • number of animals alive with sequelae
  • number of animals recovered

5.4 Other information

Any other relevant information available to facilitate assessment of the case should be provided, such as disposition to allergy, changes in feeding habits, or effects on production parameters.

When pre-mixes, which have been incorporated in medicated feeding stuffs, related to an adverse event in animals or human beings, both the pre-mix and the medicated feeding stuffs should be investigated without delay.

In addition to the standard reporting details, additional factors may need to be examined and reported. Additional important information includes the composition of the medicated feeding stuffs; with a particular focus on other medicated pre-mixes, the inclusion levels of active substances of the pre-mix, the operation of the milling process, the possibility of cross contamination and, when possible, the estimated dosage administered to individual target animals. In addition, information on feed additives may be important, when available.

5.5 Investigation

In the event of a fatal outcome the cause of death should be provided if available and its relationship to the serious adverse event commented upon. Post-mortem examination findings and laboratory results should be provided if such tests were carried out. The nature of the MAH investigation should be described, and a summary of any analysis of product samples should be provided, if relevant.

5.6 Human adverse reactions

Information about any human adverse reactions to veterinary medicines, whether occurring in conjunction with the treatment of animals, the handling of a veterinary medicine or following exposure through the environment, should be reported electronically to the VMD. The minimum information required for a human adverse reaction report is outlined in Minimum information for adverse event reports above. There should be one report per human involved in the adverse event.

The MAH should try to include, for each human adverse reaction, information on the items below in order to facilitate a full evaluation. Asymptomatic human events should be recorded but not transmitted to the VMD.

The case narrative is very important and should contain all known relevant information not otherwise reported, including how the exposure occurred, for example accidental or routine use, the degree of exposure, the volume injected or splashed, the course of events, medical diagnosis, and any other information that supports or negates an association between a veterinary medicine and an adverse event. The narrative should serve as a complete and comprehensive case report, presented in a logical time sequence in chronological order. The use of abbreviations and acronyms should be avoided.

Information facilitating a full evaluation:

• patient identification, as appropriate according to GDPR/privacy legislation. Initials or unique identifier should be provided to allow the collection of further information and to avoid any duplication of reports
• sex
• age, date of birth or adult/child
• occupation/person status, if relevant to exposure to veterinary medicine, for example veterinary surgeon, farm worker, pet owner
• date veterinary medicine used or date exposed to veterinary medicine
• date of human adverse reaction
• product details: Product/brand name, MA number, active substance and ATCvet code. This should be provided for each of the products to which the patient was exposed in the incident
• nature of exposure, including type of exposure, such as inhalation, injection, ingestion or dermal, and duration
• description of human adverse reaction including clinical signs and symptoms
• outcome of human adverse reaction, such as extent of recovery, specific treatment required
• initials and first 2 digits of postcode of medical doctor/physician, or Poison Centre, if consulted
• MAH conclusions/comments on the human adverse reaction
• animal and product administration data, for example method of administration, administration site, number and species of animals being administered the product
• status; for example veterinarian, pharmacist, other health-care professional, initials and first 2 digits of postcode of the person who reported the human adverse reaction to the MAH, if other than the patient

6. Reporting Time Frames

The MAH should transmit all adverse event reports requiring expedited reporting promptly and no later than 15 calendar days from receipt.

The date the MAH becomes aware of a report which fulfils the minimum information should be considered day 0.

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 conduct of pharmacovigilance.

All other adverse event reports may also be submitted to the VMD if MAHs would wish to use the same reporting systems as they will use for their EU MAs. In this case, adverse reports not qualifying as serious, human or unintended transmission of an infectious agent, are expected to be submitted within 30 days of the MAH becoming aware of them.

7. Reports Published in Peer-reviewed Worldwide Literature

Adverse event reports from worldwide literature are considered to be reports the MAH can reasonably be expected to be aware of. The MAH is therefore expected to monitor the scientific literature regularly to identify adverse events concerning their products that qualify for reporting.

The MAH should report to VMD published adverse events associated with the use of its veterinary medicines in accordance with the requirements for adverse event reporting described above.

Contractual arrangements may be made with a person or organisation to perform literature searches and/or report relevant individual cases to the VMD. If another person or organisation is performing these tasks, explicit procedures and detailed agreements should exist between the MAH and this person or organisation to ensure that the MAH is promptly made aware of any adverse events described in the worldwide scientific literature to ensure that the MAH can comply with their reporting obligations.

It is recommended that MAHs search the scientific literature regularly as part of their ongoing surveillance/signal detection procedures at least once a year. A risk-based approach is advised covering active substance, type of product, the stability in number and incidence of reports observed over time on the market and stability of the pharmacovigilance profile. Rather than performing a product specific search, it is recommended to begin literature searches based on the active substance which should then be narrowed down to the individual product. Search terms for ‘adverse events’ should not be too restrictive and other terms should be considered, for example adverse reaction, side effect, toxicity and idiosyncratic effect.

The MAH is expected to consider reports from other products than their own if the reaction of interest is related to the active substance and/or if the specific product cannot be identified.

The choice of databases and search criteria will be reviewed during pharmacovigilance inspections. It is preferable to ensure that a variety of databases and search engines are searched, including, for example CAB Abstracts, Google Scholar, Medline, PubMed and Scopus; the choice remains at the discretion of the MAH.

Data on resistance to a veterinary medicine from a literature search and/or other sources would be expected to be considered in the benefit:risk assessment of a product.

8. Information on Adverse Events from the Internet

MAHs should review any reports submitted through their websites and determine whether they should be reported in an expedited manner.

MAHs should consider utilising their websites to facilitate adverse event report collection, for example by providing adverse event forms for reporting or by providing appropriate contact details for direct communication.

8.1 Reports derived from the internet

Non-spontaneous adverse event reports and pharmacovigilance information may originate from an ever-increasing number of online resources. The main sources of such information that VMD is currently aware of are discussed below.

8.2 MAH hosted websites and social media accounts

Most MAHs have an active presence on the internet in the form of websites and social media accounts and many MAH hosted websites have ‘contact us’ forms.

Experience gained on pharmacovigilance inspections indicates that this route may be used to report adverse events. MAHs maintaining a presence on social media and/or the internet are encouraged to make use of these media to inform product users how to report adverse events, by providing relevant contact information and/or facilitating adverse event reporting by providing forms and the minimum information required to report an adverse event.

In any case all such potential adverse events identified via company websites or social media accounts should be followed up by MAHs, as is done for reports identified by any other means.

8.3 Groups of animal owners on the internet

Various breed organisations or associations of individuals and interest groups have fora on the internet often with discussion and chat rooms. For many animal owners their first reaction in the case of adverse events is to put a question on these for either as a warning or seeking advice.

MAHs would not be expected to trawl the internet to search for potential adverse event reports. However, if the MAH becomes aware of potential adverse events during active searches set up by the MAH, reasonable effort should be made to follow up on the reports to obtain at least the minimum reporting criteria so that the events can be channelled into the formal pharmacovigilance reporting system. In cases where the minimum criteria for a valid adverse event report have not been met after efforts to investigate the potential event, it is recommended that the MAH keeps a record of this data, for example reference to the concerned site, in line with the quality systems of the MAH.

For media sites which are hosted by the MAH or for active searches set up by the MAH, it is expected that MAHs review information from social media when made aware of a discussion of a potential safety problem to decide whether the information requires further action.

9. Reports from other sources

If a MAH becomes aware of an adverse event report from sources other than those mentioned above, for example the lay press or other media, reasonable attempts should be made to obtain the minimum information that constitutes an individual adverse event and to follow-up the report. The approach taken by the MAH for reports from other sources would be expected to be like the approach for reports identified on websites and in social media.

10. Method of Reporting

Electronic reporting of adverse events is mandatory, save in exceptional circumstances.

The electronic reporting solutions are available using the Veterinary Medicines Digital Service.

The VMD online reporting form can be used in exceptional circumstances and should be discussed directly with the VMD.

Where there are no appropriate fields in which to record specific details, the information should be provided in the case narrative as appropriate.

11. Signal Management

One of the aims of pharmacovigilance is the detection of safety signals in relation to the use of veterinary medicines. A signal is information that arises from one or multiple sources which suggests a potentially new causal association, or a new aspect of a known association, between an intervention and an event or set of related adverse events, that is judged likely to justify further investigation of possible causality. A signal should be considered as information reported on a possible causal relationship between an adverse event and a veterinary medicine, the relationship being unknown or previously incompletely documented.

The regular review and analysis of adverse events in a pre-defined time period might lead to the identification of potential signals when, for example:

• an increase in the number of adverse events in a short period is observed
• an increase in the frequency of a particular clinical sign is recorded, compared with the expected frequency for that sign
• new unidentified clinical signs are highlighted
• a potential impact on public or animal health is suspected

The MAH should have a system for continuous monitoring of the risk benefit balance of veterinary medicines via a signal management process including signal detection, prioritisation, validation, assessment, recommendation for action and documentation of outcome.

Signal management guidance will be expanded in due course.

12. Urgent Safety Restrictions

Urgent safety restrictions may be taken in the event of a risk to human or animal health or to the environment.

An urgent safety restriction is an interim change to the product information due to new information having a bearing on the safe use of the medicinal product, concerning in particular one or more of the following items in the SPC: therapeutic indications, posology, contraindications, warnings, target species, and withdrawal periods. An urgent safety restriction may be taken by the MAH to protect animal or human health. The MAH should inform the VMD immediately.

13. Reporting Following Suspension or Withdrawal of the Marketing Authorisation for Safety or Commercial Reasons

Reporting requirements remain following suspension of the MA of a veterinary medicine: see Adverse Event Reporting above and Requirements for Periodic Safety Update Reports.

Where an MA is withdrawn or revoked, the former MAH is encouraged to continue to report in line with this guidance to, for example, facilitate review of delayed onset adverse events and retrospectively notified cases. It may be appropriate to continue submission of PSURs after withdrawal or revocation of the marketing authorisation. This should be addressed and agreed on a case-by-case basis with the VMD.

14. Considerations on prioritisation of signals

This section provides a list of serious medical concepts at the level of VeDDRA Preferred Term. It is intended to be used as guidance for prioritisation and analysis of data during the signal management process, however absence of an event from this list does not exclude that event from analysis.

Preferred Terms	Species
All	Human
Abdominal pain	Horse
Abomasitis	Ruminant, Camelid
Abortion	All
Acute mastitis	Ruminant, Camelid, Horse
Aggression	All
Anaphylaxis	All
Anorexia	Horse
Apnoea	All
Ataxia	Horse
Bee systemic disorder NOS	Bee
Birth defect	All
Blindness	All
Bone marrow hypoplasia	All
Cardiac arrest	All
Cardiac insufficiency	All
Circulatory shock	All
Coagulopathy	All
Collapse NOS	All
Coma	All
Convulsion	All
Deafness	All
Death	All
Diabetes mellitus	All
Disseminated intravascular coagulation	All
Dyspnoea	All
Epileptic seizure	All
Fish asphyxia	Fish
Fish body deformity	Fish
Haemolytic anaemia	All
Haemorrhagic gastroenteritis	All
Heart block	All
Hepatic failure	All
Hypersensitivity reaction	All
Hypocalcaemic condition	Ruminant, Camelid
Hypomagnesaemic condition	Ruminant, Camelid
Impaired hearing	All
Impaired vision	All
Immune mediated thrombocytopenia	All
Increased coagulation time	All
Injection site sarcoma	All
Ketosis	Ruminant, Camelid
Laminitis	Horse
Loss of consciousness	All
Lying down	Horse, Ruminant, Pig, Camelid
Metastatic neoplasia	All
Metritis	All
Moribund	All
Multi-organ failure NOS	All
Myoglobinuria	Horse
Paralysis	All
Paresis	All
Perinatal mortality	All
Recumbency	Horse, Ruminant, Pig, Camelid
Renal insufficiency	All
Reticulitis	Ruminant, Camelid
Stillbirth	All
Suspected infectious agent transmission	All
Thrombocytopenia	All

14.1 Table of clinical signs of anaphylactic shock reactions in different species

Anaphylactic shock is an acute allergic, potentially life-threatening, Type 1 hypersensitivity reaction resulting from the generalised release of potent vasoactive substances from mast cells and basophils. The clinical signs of anaphylaxis can vary depending on the major so-called “shock organ” relevant to the species. The table below summarises the differences between species, however this list is not exhaustive.

Species	Major shock organ(s)	Pathology	Clinical signs
Dogs	Liver	Hepatic and intestinal engorgement, visceral haemorrhage	Initially excitement, urticaria, angioedema and pruritus, then vomiting and defecation. Finally collapse, dyspnoea and convulsions
Cats	Respiratory tract / Gastrointestinal tract	Bronchoconstriction, pulmonary haemorrhage, oedema and emphysema, oedema of the glottis	Initially angioedema and pruritus around the face, then salivation, dyspnoea, vomiting, incoordination and collapse
Rabbits	Respiratory tract / Cardiovascular system	Pulmonary artery vasoconstriction and right ventricular failure	Initially tachypnoea, dyspnoea and pallor, then collapse, defecation and urination, loss of consciousness or collapse and convulsions
Horses	Respiratory tract / Gastrointestinal tract	Pulmonary oedema and emphysema, intestinal oedema and haemorrhage	Initially shivering, sweating and incoordination. Possibly coughing, dyspnoea and diarrhoea. Finally collapse. Colic
Cattle and sheep	Respiratory tract	Pulmonary haemorrhage, oedema and emphysema	Initially urticaria, angioedema, pruritus and restlessness. Coughing, severe dyspnoea and cyanosis. Also, defecation, urination, bloat and collapse
Pigs	Respiratory tract / Gastrointestinal tract	Pulmonary oedema and emphysema, intestinal oedema and haemorrhage.	Dyspnoea, cyanosis, pruritus and collapse