The European Agency for the Evaluation of Medicinal Products

Veterinary Medicines and Inspections

EMEA/CVMP/183/96- Rev.1-CONSULTATION

COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS

GUIDELINE ON

PHARMACOVIGILANCE FOR VETERINARY MEDICINAL PRODUCTS

– GUIDANCE ON PROCEDURES FOR MARKETING AUTHORISATION HOLDERS

ADOPTION BY CVMP 15-17 July 1997

DATE FOR COMING INTO OPERATION 1 January 1998

REVISED BY PHARMACOVIGILANCE WORKING PARTY 12-13 January 2004

ADOPTION BY CVMP FOR RELEASE FOR CONSULTATION 17 March 2004

START OF CONSULTATION 18 March 2004

END OF CONSULTATION 17 September 2004

Public 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK

Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 84 47
E-mail: [email protected] http://www.emea.eu.int

EMEA 2004 Reproduction and/or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged
 GUIDELINE ON PHARMACOVIGILANCE FOR VETERINARY
MEDICINAL PRODUCTS – GUIDANCE ON PROCEDURES FOR MARKETING
AUTHORISATION HOLDERS

1. LEGAL BASIS AND PURPOSE

The legal framework for pharmacovigilance of veterinary medicinal products in the Community is
given in Council Regulation (EEC) No 2309/93 (Title III, Chapter 3), Commission Regulation (EC)
No 540/95 and Directive 2001/82/EC of the European Parliament and of the Council (Title VII).

Pharmacovigilance activities come within the scope of the criteria of quality, safety and efficacy, as
new information is accumulated on the veterinary medicinal product under field conditions of use in
the marketing situation. Pharmacovigilance obligations apply to all authorised veterinary medicinal
products.

Council Regulation (EEC) No 2309/93 (Articles 41 to 44), Commission Regulation (EC) No 540/95
and Directive 2001/82/EC (Title 1 Definitions, Article 1 and Title VII Pharmacovigilance, Articles 72
to 79) describe the respective obligations of the person responsible for placing the veterinary
medicinal product on the market (the Marketing Authorisation Holder, MAH), and of the competent
authorities to set up a system for pharmacovigilance in order to collect, evaluate and collate
information about suspected adverse reactions. All relevant information should be shared between the
competent authorities and the MAH, in order to allow the partners in pharmacovigilance activities to
assume their obligations and responsibilities. This requires an exchange of information between the
EMEA, hereafter referred to as the Agency, the competent authorities of the Member States, and the
MAH, as well as procedures to avoid duplications, maintain confidentiality and ensure the quality of
the systems.

Norway, Iceland and Liechtenstein are part of the EEA (European Economic Area) together with the
Member States of the European Union. The EFTA (European Free Trade Association) States Norway,
Iceland and Liechtenstein have, through the EEA-agreement, adopted the complete Community acquis
on medicinal products and are consequently parties to the Community procedures.

Where in this Guideline reference is made to Member States of the Community, this should therefore
be read to include these EFTA states.

The only exemption from this is that legally binding acts from the Community (e.g. Commission
decisions) do not directly confer rights and obligations but have first to be transposed into legally
binding acts in these EFTA states. According to Decision No 74/1999 of the EEA Joint Committee
when decisions on approval of medicinal products are taken by the Community, these EFTA states
will take corresponding decisions on the basis of relevant acts. Consequently, these EFTA states are
concerned by the single European market for medicinal products.

In accordance with Article 46 of the Regulation and Article 77 of the Directive, guidance on the
implementation and practical procedures involved in complying with the above legislation, in the
interests of protecting public and animal health, shall be prepared and published by the European
Commission, in Volume 9 of The Rules Governing Medicinal Products in the European Union, based
on guidelines drafted by the CVMP and any other international harmonisation work carried out in the
field of pharmacovigilance.

The areas covered are set out in the paragraphs that follow:

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2 SCOPE

The scope of veterinary pharmacovigilance as defined in Article 73 of Directive 2001/82/EC covers

not only safety aspects in animals and in humans related to veterinary medicinal products, but also
other aspects of post-authorisation surveillance. The system also takes into account any available
information arising from the use of veterinary medicinal products, such as:
• lack of expected efficacy of a veterinary medicinal products;
• adverse reaction reports related to off-label use;
• reported violations of approved residue limits, possibly leading to investigations of the
validity of the withdrawal period;
• potential environmental problems;

For veterinary medicinal products authorised in the Community (whether through the centralised or
national procedures, including mutual recognition):
all suspected adverse reactions (serious or otherwise) should be reported when received from
veterinarians, other animal health professionals, animal owners or users of the veterinary medicinal
product. For the accuracy and usefulness of the information reported, it is recommended for animal
owners and users to seek veterinary advice prior to reporting. Suspected adverse reactions should be
reported even if the MAH does not agree with the reporter’s assessment of a possible causal
association. These include spontaneously reported suspected adverse reactions and suspected adverse
reactions from post-authorisation surveillance studies.

In the following this guideline will not include the word ‘suspected’ when making reference to adverse
reactions, serious adverse reactions, human adverse reactions, or lack of expected efficacy, however
these terms should be understood to address suspected adverse reactions or events. When making
reference to adverse reactions by acronym this guideline will use ‘SAR’ as in ‘Suspected Adverse
Reaction’, in preference to the previously used acronym ‘ADR’ (adverse drug reaction).

2.1 Reporting of human adverse reactions to veterinary medicinal products

All adverse reactions occurring in humans following use of veterinary medicinal products whether
occurring in conjunction with the treatment of animals, the handling of a veterinary medicinal product
or following exposure through the environment should be reported immediately by the MAH, and in
no case later than 15 calendar days following receipt, to the competent authorities of the Member State
in whose territory the incident occurred (see section 7 for details of what to report).

2.2 Reporting of lack of expected efficacy

Directive 2001/82/EC cites the lack of efficacy as a reason for refusal or revocation of authorisation.

It may be defined as the apparent inability of an authorised product to have the recognised efficacy in
an animal, according to the claims of the SPC and following use of the product in accordance with the
SPC. Report of lack of expected efficacy should not normally be expedited (i.e. report within 15 days
after receipt), but should be discussed in the relevant Periodic Safety Update Report (PSUR) (see
section 6). However, in certain specific circumstances, e.g. where a change to a condition of use of a
marketing authorisation might be necessary in order to safeguard the continuing efficacy of the
product, reports of lack of expected efficacy of veterinary medicinal product may be recorded and
reported promptly to the competent authorities. The “European Veterinary Pharmacovigilance
reporting form” attached in Table A should be completed, as appropriate (see section 5.3.10).

It is also important to identify if the lack of expected efficacy is a due to a possible quality batch
problem. However, quality-related issues must be reported according to the relevant requirements (see
Revised Compilation of Community Procedures on Administrative Collaboration and Harmonisation

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of Inspections, Procedure for Handling Rapid Alerts and Recalls Arising from Quality Defects
(http://www.emea.eu.int/Inspections/docs/335103en.pdf).

2.3 Off-label use

Off-label use: the use of a veterinary medicinal product that is not in accordance with the
summary of the product characteristics, including the misuse and serious abuse of the product1

Reports of adverse reactions may be obtained;

- on products used outside the terms of the marketing authorisation e.g. use of a product in non-
authorised species/indications, use at doses differing from those set out in the summary of product
characteristics (SPC) and package insert (Products with national authorisations should follow the
national SPC and products with Community authorisations should follow the unique EU SPC.)
- on products used outside the terms of the marketing authorisation but in conformity with the
provisions of Article 10 of Directive 2001/82/EC.

Such reports can provide useful information on the safety of the given medicinal product and should
be recorded by the person responsible for pharmacovigilance and reported to the competent authorities
in the same way as for all adverse reactions. The “European Veterinary Pharmacovigilance reporting
form” attached in Table A should be used, as appropriate (see section 5.3.10).

2.4 Premixes for medicated feedingstuffs2

When premixes which have been incorporated in the medicated feedingstuffs are suspected of causing
an adverse reaction in animals or humans, both the premix and the medicated feedingstuffs should be
investigated without delay.

Among the factors that have to be examined and reported, if appropriate, are the composition of the
medicated feedingstuffs, the inclusion levels of active substances of the premix, the operation of the
milling process(es) and, when possible, the estimated dosage administered to individual target
animals.

2.5 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 medicinal product when testing bulk milk
for antibiotics
- Analytical laboratories or food producers who routinely monitor foodstuffs for residues for
instance in slaughterhouses or dairies
- State or regional veterinary authorities conducting statutory or other residue surveillance on food
for food producing animals.

The report should contain details about the source of the report, the veterinary medicinal product and
active substance, including marketing authorisation number and batch number if available, date of use
and date of detection of the residues, the location of the case, the species and details of the residues
detected. The report should also contain details about the steps taken by the MAH. The “European
Veterinary Pharmacovigilance reporting form” attached in Table A should be completed as
appropriate (see section 5.3.10).
Where veterinary medicinal product residues in tissues or food products of treated food producing
animals cast doubt on the validity of the withdrawal period of the given veterinary medicinal product,

1 as defined in Article 1(16) of Dir. 2001/82/EC

2 as defined in Article 1(5) of Dir. 2001/82/EC

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this information should be reported to the relevant competent authority responsible for authorisation of
the veterinary medicinal product concerned. Reports which cast doubts on the validity of withdrawal
periods should not normally be expedited (i.e. reported within 15 days after receipt), but should be
discussed in the relevant PSUR (section 6). However, in certain specific circumstances, reports
regarding the validity of the withdrawal period of the veterinary medicinal product should be recorded
and reported promptly to the competent authorities.

2.6 Potential environmental problems

A potential environmental problem is a situation where animals (non-target), humans or plants may be
adversely affected through exposure to a veterinary medicinal product present in the environment.

Any suspected environmental problem related to its veterinary medicinal products should be recorded
by the MAH as soon as it comes to his knowledge. The minimum requirements for any potential
environmental problem to be recorded by the MAH and reported to the concerned competent
authorities are: the location, the animal species involved, the nature of the suspected environmental
problem and the suspected product(s). The “European Veterinary Pharmacovigilance reporting form”
attached in Table A should be completed as appropriate (see section 5.3.10) and used for reporting to
the competent authorities.

Reports of potential environmental problems should not normally be expedited (i.e. report within 15
days after receipt), but should be discussed in the relevant PSUR (section 6). However, in certain
specific circumstances, in order to limit further environmental damage, reports of potential
environmental problems related to the veterinary medicinal product, should be recorded and reported
promptly to the competent authorities.

3. Responsibilities of Marketing Authorisation Holders

The responsibilities of the qualified person responsible for pharmacovigilance are as follows:

3.1 the establishment and maintenance of a system which ensures that information about all
adverse reactions which are reported to the personnel of the MAH, including representatives, is
collected and collated so that it may be accessed at least one point within the Community, as indicated
by the MAH;

3.2 the preparation and submission of the following documents for Agency and/or competent
authorities of Member States where the veterinary medicinal product is authorised as referred to in the
Regulation and Directive and further detailed in this document:
• Serious adverse reaction reports in animals

• Reports of adverse reactions in humans

• Periodic safety update reports (PSURs) to include:

- risk/benefit evaluation during the post-authorisation period, covered by the PSUR;
- all (serious and non-serious) spontaneous adverse reaction reports in animals
- all adverse reactions reports in humans
- any available information on;
- lack of expected efficacy
- adverse reactions reports related to off-label use
- potential environmental problems
- investigations of the validity of the withdrawal period due to reported violations of

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 approved Maximum Residue Limits (laid down in Council Regulation (EEC) No
2377/90 as amended).

3.3 Ensuring that any request from the competent authorities in any of the Member States of the
EU, for the provision of additional information necessary for the evaluation of the benefits and risks
afforded by a veterinary medicinal product, is answered fully and promptly. This includes the
provision of information about the volume of sales of the veterinary medicinal product concerned;

3.4 Products authorised under Article 13(1)(a)(i) of Directive 2001/82/EC:

The MAHs for both the original reference product (Product A) and the essentially similar product
(Product B, authorised according to Article 13(1)(a)(i) of Directive 2001/82/EC) assume full
responsibility for the pharmacovigilance relating to their respective veterinary medicinal products.

Nevertheless they should maintain close liaison, and in particular adverse reactions to Product B must
be communicated to the MAH for Product A. Where identical products are co-marketed by more than
one company any report of a serious adverse reaction must be communicated by one company to the
other one. Any regulatory action resulting from pharmacovigilance information related to the products
involved in the above scenarios would need to be applied as appropriate to both products.

3.5 If the MAH is aware that a reporter has reported an adverse reaction to one of its products
directly to the competent authority of a Member State, the MAH should still report the adverse
reaction, informing the competent authority that the report is likely to be a duplicate of a previous
report. In this situation it is essential for the MAH to provide all the available details, including any
reference number provided to the reporter by the authority, in order to aid identification of the
duplicate.

4. Adverse Reaction Reporting

Adverse Reaction3: A reaction which is harmful and unintended and which occurs at doses
normally used in animals for the prophylaxis, diagnosis or treatment of disease or the
modification of physiological function.

4.1 The MAH is responsible for reporting adverse reactions to the competent authorities of the
Member States and EMEA for their veterinary medicinal products authorised under the centralised
procedures and to the appropriate competent authorities of the Member States for their medicinal
products authorised through the national procedures (for details of the reporting requirements see
sections 5 to 7).

4.2 Minimum requirements for any adverse reaction (serious/non-serious/human) report to

be recorded by the MAH, and reported to the competent authorities in the Member State and/or the
Agency as appropriate, see event charts in Annex I for details:

A case report will be considered as an adverse reaction report provided that at least the following data
are available:
(i) an identifiable source, wherever possible this should include name and address of the reporter
(e.g. veterinarian, pharmacist, animal owner)
(ii) animal details: species, sex, age / human details: sex, age or adult/child
(iii) veterinary medicinal product concerned - (name and marketing authorisation number)

3 Also referred to as suspected adverse reaction (SAR)

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(iv) adverse reaction details

The reference point for deadlines for submission of reports is the time of receipt of the minimum
information. It should be stressed that these are minimum requirements and that companies should
endeavour to provide all the information necessary for a full evaluation. (See sections 5.3 and 6.3 for
details of information required). Follow-up reports on incomplete adverse reaction reports should be
submitted by the MAH, in particular in cases where only the minimum information was submitted
within 15 days, however in general whenever relevant further information becomes available, or at
least when the investigation of the adverse reaction is completed.

4.3 Reports from post-authorisation studies

During the post-authorisation period the veterinary medicinal product will be used in a different
setting from clinical trials and larger populations are likely to be exposed. Much new information will
be generated which may impact on the risk/benefit ratio and an evaluation of this needs to be an on-
going process, both within pharmaceutical companies and regulatory authorities.

Compared to human medicine, the tolerance of veterinary medicinal products is more predictable since
it is studied in the target species at supra-therapeutic doses, which allows for the evaluation of a
margin of safety. Therefore the need for post authorisation surveillance studies is certainly not so
stringent in the veterinary field. Spontaneous reporting schemes are expected to provide the
complementary information concerning adverse reactions, especially those that are unexpected.
However, for specific cases concerning adverse reactions occurring for products used on a large scale
such as post-vaccinal adverse reactions, post authorisation studies should be encouraged.

The methodology for such studies is obviously quite specific to the veterinary field and should be
considered as an area for investigation in veterinary pharmacovigilance, and will be the subject of
further guidelines. Serious adverse reactions from post-authorisation studies should be reported to all
Member States where the product is authorised (see section 5 for reporting requirements). Non-serious
adverse reactions should be reported in summary at the end of each post-authorisation study and
included in the PSUR (see section 6).

5. Serious Adverse Reaction Reporting Requirements

Serious Adverse Reaction: An adverse reaction which results in death, is life-threatening, results
in significant disability or incapacity, is a congenital anomaly/birth defect or which results in
permanent or prolonged signs in the animals treated.

In veterinary medicine the existence of a large diversity of animal species and husbandry conditions
require a modified approach to the classification of a ‘serious adverse reaction’ (‘serious SAR’). For
example in intensive 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 and
only an increased of mortality rate, or severe signs, or variations of animal production levels
exceeding the rates normally expected should be considered as a ‘serious SAR’.

However, in species like dogs, cats or horses a single death constitutes a ‘serious SAR’. This also
applies to cases of individual deaths in cattle, sheep, pigs, goats and rabbits even if they are kept in
herds or flocks in intensive animal production because treatment is often performed on the individual
animal and therefore a single death or severe symptoms have to be considered on an individual basis.

Note: For all species if kept as an individual animal, a single death constitutes a ‘serious SAR’.

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5.1 Adverse reaction reports occurring in the EU

Article 44 of Council Regulation (EEC) No 2309/93 and Article 75 of Directive 2001/82/EC provide
the Community requirements for adverse reactions reporting.

The MAH should record and report all serious adverse reactions occurring within the Community,
which are brought to its attention. These should be reported immediately, and in no case later than 15
calendar days from receipt, to the Member State in whose territory the serious SAR occurred (see
section 5.3 for details of what information is required).

For centrally authorised products, the responsibility for ensuring that all serious adverse reactions to
such products occurring within their territory are further reported to the Agency, rests with the
Member States concerned. Such reports must be submitted to the Agency immediately and in no case
later than 15 days following receipt of the information

In addition, serious adverse reactions together with all other adverse reactions should be reported as
line listings in the PSUR (see section 6).

5.2 Adverse Reaction reports occurring outside the EU

Article 44 of Council Regulation (EEC) No 2309/93 and Article 75 of Directive 2001/82/EC provide
the Community requirements for adverse reactions reporting.

The MAH should report all serious and unexpected4 adverse reactions occurring in the territory of a
third country and brought to its attention. These should be reported immediately, and in no case later
than 15 calendar days following receipt to the Agency and to all Member States for all centrally
authorised products, and to the concerned Member States for nationally authorised products.

In addition, all adverse reactions from third countries should be reported as line listings in the PSUR
(see section 6).

A general overview on the reporting of adverse reactions (Serious/non-serious/human;

Unexpected/expected) in relation to the type of authorisation (centrally or nationally authorised,
including mutually recognised) is presented in the Event Charts in Annex I.

5.3 Content/Required information for serious adverse reactions (single) reports

MAHs are expected to fully validate and follow-up all serious adverse reactions reported by them to
the authorities. It is essential for MAHs to provide as complete as possible details, including all
relevant clinical information for cases of serious adverse reactions in order to facilitate assessment.
The report of a serious adverse reaction should as far as possible include the information below. The
original words used by the reporter should be provided even if they are also classified or coded
according to MAH or competent authority accepted terminology.

5.3.1 Marketing Authorisation Holder (MAH) details and original reporter’s details
i) The name of the qualified person responsible for pharmacovigilance employed by the MAH.
ii) Address, telephone and fax number of the qualified person.
iii) MAH case reference number.

4 Unexpected Adverse Reaction: This means an adverse reaction the nature, severity or outcome of which is
not consistent with the summary of the product characteristics, as defined in Article 1.13. of Dir. 2001/82/EC

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iv) Date of receipt of report by MAH (in country of qualified person responsible for
pharmacovigilance).
v) Source of report e.g. spontaneous, clinical trial, post-authorisation study.
vi) Details of the original reporter - name (if acceptable under national law), address, profession
and speciality (if available).
vii) Reporting country (country where the incident occurred).
viii) Purchase country (where suspect product was purchased if different from that above).

5.3.2 Animal Details

i) Number treated
ii) Characteristics of animals showing signs:
• Species
• Breed
• Sex
• Age (in days/weeks/months/years)
• Weight (in kilograms)

5.3.3 Suspect veterinary medicinal product details

i) Product name(s)/brand names(s)
ii) Approved Scientific Name(s) (INN - International Non-proprietary Name)
iii) Marketing Authorisation Number
iv) ATCvet Code (Therapeutic Group)
v) Pharmaceutical form
vi) Batch number
vii) Expiry date of batch - if relevant
viii) Storage details - if relevant

5.3.4 Treatment details

i) The person who administered the veterinary medicinal product (e.g. animal owner, veterinary
surgeon etc.). Include identifier (name/initials) and relevant occupation/qualification of
person.
ii) Reason for treatment including diagnosis
iii) Dose (and frequency if relevant) of treatment given
iv) Route and site of administration used
v) Start date
vi) Stop date and/or duration of treatment
vii) Time between administration and adverse reaction to the product

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viii) Action taken after reaction (e.g. product withdrawn, dose reduced)
ix) Previous adverse reaction(s) to the product if occurred/reported, (re-challenge information) to
include:
• Approximate date animal(s) previously treated with product
• Description of adverse reaction including - were previous reaction signs similar to the
present reaction signs
• Outcome including any treatment given

5.3.5 Other products used concurrently

All medicinal treatment over at least a one-week period preceding the adverse reaction should be
provided when available. This should also include non-prescription medicines, magistral preparations5
and medicated feedingstuffs if applicable.

For each medication:

i) Product name(s)/brand names(s)
ii) Approved Scientific Name(s) (INN - International Non-proprietary Name)
iii) Marketing Authorisation Number
iv) ATCvet Code (Therapeutic Group)
v) Pharmaceutical form
vi) Batch number if relevant
vii) Expiry date of batch - if relevant
viii) Storage details - if relevant

Treatment details for other product(s) used concurrently

ix) The person who administered the product (e.g. animal owner, veterinary surgeon etc.) Include
identifier (name/initials) and relevant occupation/qualification of person
x) Dose (and frequency if relevant) of treatment given
xi) Route and site of administration used
xii) Start date
xiii) Stop date and/or duration of treatment
xiv) Other relevant information

5.3.6 Details of the animal adverse reaction(s

i) Description of adverse reactions(s) including site and severity (intensity of the reaction). The
initial reporter’s words and/or phrases to be used where possible (with explanations if
appropriate).
ii) Start date or onset of reaction
iii) Stop date or duration of reaction

5 In the case of magistral products, details of individual constituents of the formula should be indicated.

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iv) Specific treatments adopted against the observed adverse reaction
v) Number of animals showing signs
vi) Number of animals dead
vii) De-challenge information (e.g. any obvious effect of removal of treatment)
viii) If available the following information should be provided:
- Number of treated animals alive with sequelae
- Number of treated animals recovered

Any previous adverse reactions to the given product should be recorded under 5.3.4 ix).

5.3.7 Other information

Any other relevant information available to facilitate assessment of the case should be provided, for
example: disposition to allergy or changes in feeding habits, and/or production rates.

5.3.8 Investigation

- In a case of fatal outcome the cause of death should be provided and its relationship to the
serious adverse reaction commented upon. Post-mortem examination findings or laboratory
findings, if carried out, should be provided.

- Summary of product sample investigation (if relevant)

- Nature of MAH investigation (if relevant)

5.3.9 Causality assessment

MAHs may comment on whether they consider there is a causal association between the suspected
veterinary medicinal product(s) and adverse reactions(s) reported and should provide the criteria on
which they have made the assessment.

The causality assessment should be done using the ABON-system if possible. According to this
system, four categories of causality can be made:

• category "A": probable

• category "B": possible

• category "O"6: unclassifiable/unassessable (cases where insufficient information was

available to draw any conclusion)

• category "N": unlikely to be drug related

In assessing causality the following factors should be taken into account:

i) associative connection, in time - including dechallenge and rechallenge following repeated
administration (in clinical history) - or in anatomic sites;

6 Where there is a possibility that an SAR could be related to treatment but present data is not enough to draw a
conclusion, it has proved to be useful to create working subcategories for O: O1 – inconclusive (cases where
other factors prevent a conclusion being drawn, but a product association cannot be discounted) and O-2
unclassified (cases where insufficient or unreliable information did not allow to draw any conclusion).

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ii) pharmacological explanation, blood levels, previous knowledge of the drug;
iii) presence of characteristic clinical or pathological phenomena;
iv) exclusion of other causes;
v) completeness and reliability of the data in the case reports;
vi) quantitative measurement of the degree of contribution of a drug to the development of a
reaction (dose-effect relationship).

For inclusion in category "A" (probable), it is recommended that all the following minimum
criteria should be complied with:
• There should be a reasonable association in time between the administration of the veterinary
medicinal product and onset and duration of the reported event.
• The description of the clinical phenomena should be consistent with, or at least plausible, given
the known pharmacology and toxicology of the product.
• There should be no other equally plausible explanation(s) of the case. (If such are suggested - are
they validated? What is their degree of certainty?) In particular, concurrent use of other products
(and possible interactions) or intercurrent disease should be taken into account in the assessment.

Where any of the above criteria cannot be satisfied (due to conflicting data or lack of information)
then such reports can only be classified as "B" (possible), "N" (unlikely) or "O"
(unclassifiable/unassessable).

For inclusion in category "B" (possible), it is recommended that this be applied when veterinary
medicinal product causality is one (of other) possible and plausible causes for the described event but
where the data does not meet the criteria for inclusion in category "A".

For inclusion in category "N" (unlikely), cases where sufficient information exists to establish
beyond reasonable doubt that veterinary medicinal product causality was not likely to be the cause of
the event.

For inclusion in category "O" (unclassifiable/unassessable), all cases where reliable data
concerning a SAR is unavailable or is insufficient to make an assessment of causality.

Further guidance on how to carry out causality assessment will be published in a separate guideline.

5.3.10 Reporting forms

For the reporting of adverse reaction (in animals or in humans) by the MAH to competent authorities
and for the reporting of any available information as lack of expected efficacy, adverse reactions
related to off-label use, investigations of the validity of the withdrawal period or potential
environmental issue, the “European Veterinary Pharmacovigilance reporting form” attached at Table
A should be used. Computer-generated forms are acceptable provided they are legible and follow the
accepted content and layout. Reports should be in the national language(s), or in English if this is
acceptable to the appropriate competent authorities.

The EudraVigilance Veterinary project, which is a system for electronic exchange of

pharmacovigilance data has been released for testing in July 2003 and will gradually replace the need
for paper reporting. MAHs are encouraged to register to EudraVigilance Veterinary (see
http://erstest.emea.eu.int/vet).

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6. Periodic Safety Update Reports (PSURs)

A Periodic Safety Update Report (PSUR) is intended to provide competent authorities with an update
of the world-wide safety experience of a veterinary medicinal product at defined times post-
authorisation. At these times MAHs are expected to provide succinct summary information together
with a critical evaluation of the risk/benefit of the product in the light of any new or changing post-
authorisation information. This is in order to ascertain whether further investigations need to be
carried out and/or whether changes should be made to the SPC, labelling or product promotion.

For centrally authorised veterinary medicinal products, PSURs should be submitted to all Member
States competent authorities and the Agency in accordance with Article 44 of Regulation (EEC) No
2309/93.

For other veterinary medicinal products;

- authorised within the scope of Directive 87/22/EEC (ex-concertation procedure) or;
- that have benefited from the mutual recognition procedure in accordance with Directive
2001/82/EC or;
- that have been subject to referrals under Article 36, 37 and 38 of Directive 2001/82/EC or;
- other nationally authorised,
PSURs should be submitted to the competent authorities of the concerned member states in
accordance with Article 75 of Directive 2001/82/EC.

The requirement for the submission of a PSUR applies irrespective of whether the veterinary
medicinal product is marketed or not.

6.1 Scope

In compliance with the requirements laid down in Directive 2001/82/EC holders of marketing
authorisations must include in the PSURs of all veterinary medicinal products, whether authorised
nationally or through the centralised procedure, details of all adverse reactions arising in the
Community or in a third country.

The PSUR should include information on the following types of adverse reaction reports/case histories
received during the period of review:
• All adverse reactions in animals and in humans, sent spontaneously to the MAH
• All adverse reactions forwarded to the MAH by the Competent Authority.
• Serious and non-serious SAR reports from post-authorisation studies (see section 4.4).
• Any available information on investigation of insufficient withdrawal period, lack of expected
efficacy, adverse reactions related to off-label use or any potential environmental problems,
caused by the product under the normal conditions of use.

6.2 Frequency and timing of reports

Unless other requirements have been laid down as condition of the granting of authorisation, a PSUR
should be prepared for all authorised veterinary medicinal products at the following intervals:
- immediately upon request
- 6-monthly for the first 2 years after authorisation
- annually for the subsequent 2 years
- at the time of the first renewal (4.5 years after first authorisation)

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- thereafter 5-yearly at the time of further renewal.

If in accordance with Article 75(6) of Directive 2001/82/EC a MAH seeks to amend the frequency
with which PSURs for a veterinary medicinal product authorised in accordance with the directive are
submitted to the relevant Competent Authority(ies), such an application should be supported by
reasoned argument.

Each PSUR should cover the period of time since the last update report and should be submitted
within 60 days after the Data Lock Point (DLP)7.

Data lock points may be set according to the EU Birth Date (date of the first marketing authorisation
within the European Union) of a medicinal product or its International Birth Date.

Preparation of PSURs according to the International Birth Date:

Veterinary medicinal products, which are also authorised outside the EU, will have an International
Birth Date (IBD). This is the date of the first marketing authorisation for the product granted to the
MAH in any country in the world. For veterinary medicinal products first authorised in the EU, the
EU Birth Date is the IBD. For administrative convenience, if desired by the MAH, the IBD may be
designated as the last day of the same month.

In order to harmonise PSURs internationally, the MAH may use the IBD to determine the data-lock
points in the EU rather than the EU Birth Date. If the IBD is used, the first data lock point must be
within 6 months of the EU Marketing Authorisation Date, unless other requirements have been laid
down at the time of granting the authorisation. Regardless of whether the IBD or EU Birth Date is
used, the PSUR must always be submitted within the 60 days following the data lock point.

The MAH should submit the renewal application at least three months before the expiry date of the
marketing authorisation in the EU. This may be submitted earlier in order to facilitate co-ordination
with the regular cycle of the PSUR, but should not be more than 6 months before expiry of the
authorisation. At the time of the renewal application the MAH should submit a PSUR no more than 60
days after the data lock point, which should cover the intervening time period since the last PSUR. For
centrally authorised veterinary medicinal products further guidance is given in the CVMP Guideline
on the processing of renewals in the centralised procedure (EMEA/CVMP/695/01).

For the purpose of the PSUR the MAHs database should be frozen in relation to the product at the
DLPs. Up-to-date safety data, i.e. data that becomes known to the MAH after the DLP and which may
influence the evaluation should also be included in the report in the final section (see section 6.4.7).

For veterinary medicinal products authorised under the centralised procedure in accordance with
Council Regulation (EEC) No 2309/93 the PSUR should cover all authorised presentations covering
all pharmaceutical forms and target species, whether authorised with the original marketing
authorisation or at a later time point, e.g. through an extension of the marketing authorisation. For
each subsequent variation to the original marketing authorisation it will be decided on a case-by-case
basis whether the submission cycle for the PSUR needs to be changed. The data lock points remain
based on the date of the original marketing authorisation.

6.3 Content of Periodic Safety Update Reports

For a Community authorised product, the PSUR should be written in English. For nationally
authorised products, the PSUR should be written in the national language(s), or in English if this is
acceptable to the appropriate competent authorities.

7 Data Lock Point (DLP): The date designated as the cut-off date for data to be incorporated into a particular
PSUR. On this date the data available to the author of the PSUR is extracted for review and stored.

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For marketed products, PSUR should fulfil the following format and content:

6.3.1 Marketing Authorisation Holder (MAH) and product details

Each PSUR should include:

i) The name of the MAH
ii) The product name(s)
iii) The marketing authorisation number(s)
iv) The period covered by the PSUR

6.3.2 SPC (Articles 12 and 14 of Directive 2001/82/EC)

The latest version of the relevant SPC must be included for reference in the report.
• For products authorised through the Centralised or Mutual Recognition procedures, this will be
the centrally or mutually accepted SPC in English.
• For products authorised nationally, the specific national SPC in the language of the Member State
concerned should be included.

If no SPC is available, e.g. in cases of old non-reviewed/renewed products, an explanation should be

given and the package insert should be provided.

6.3.3 Narrative review of individual case histories

The report should include a narrative based on the MAHs analysis of the cases reported during the
period concerned by the PSUR. Information on the individual adverse reaction reports should be
presented as a line listing. The line listing should be provided as an appendix (see section 6.4.8).

It will be necessary, in a given report, to separate data relating to different formulations (dosage
form(s) and strength(s)). Within formulation, the safety data should be further differentiated based on
target species (if the veterinary medicinal product is authorised for use in more than one species),
reaction type (that is, serious, non-serious, human reaction, etc.), and then country where the report
originated.

6.3.4 Incidence of Adverse Reactions

A PSUR must address the relationship between the sales volume of a product and the numbers of
adverse reactions reported.

6.3.4.1 Sales volume

For nationally authorised products, each PSUR should contain the number of doses/amount of product
sold in the relevant Member State(s). For Community authorised products, each PSUR should contain
the number of doses/amount sold in each Member State. The sales information should be expressed in
an appropriate form.

The following forms are suggested:

• Vaccines to be expressed in numbers of doses;
• Liquid to be expressed in litres;
• Powder to be expressed in kilograms;

Public EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 Page 15/28

• Tablets to be expressed in numbers of tablets;
• Sprays to be expressed in litres or kilograms;
• Flea collars to be expressed in numbers of collars;
• Paste to be expressed in kilograms

6.3.4.2 Calculation of Incidence of adverse reactions

It is suggested that MAHs adopt a two-tier approach to calculation of incidence of adverse reactions.

STEP 1:
In the first instance, the ratio of the number of animals reacting during a period to the amount of
product sold during that period should be computed:
No of animals reacting during period : No of doses sold during period

This calculation is based on data that tends to be accurate and can be used reliably to monitor trends
from one PSUR to the next. Any increase in this ratio relative to previous PSURs may signal a
problem and the need for more detailed evaluation of the pharmacovigilance data. For PSURs
submitted with applications for product authorisation renewal (beginning with the second renewal),
sales volume should be broken down by calendar year and the ratio of the number of animals
adversely reacting to the amount of product sold should be computed for each of the years concerned
by the report.

STEP 2:
The incidence (%) of adverse reactions should be calculated by dividing the total number of animals
reacting during the period by an estimate of the number of animals treated during the period of the
report and multiplying by 100.
No of animals reacting during period x 100
% Incidence =
Estimated No of animals treated during the period

For both national and community authorised products, incidence should be calculated individually for
each country. In the first instance, it is expected that % incidence will be calculated based on the total
number of animals reacting during a period derived from all A, B and O coded reports. This
calculation may then be revised to exclude O coded reports (that is, this final calculation focuses on A-
probable- and B-possible- coded reports only).

The values included in the calculation of incidence must be justified. It is expected that the values
used for estimation of the number of animals treated would be representative of the conditions of use
of the veterinary medicinal product. When calculating the number of animals treated during a period,
the following points should be taken into consideration:
• For some veterinary medicinal products , the number of doses (individual units) sold is equivalent
to the number of animals treated (e.g. anthelmintic boli, flea collars). For veterinary medicinal
products formulated as pastes, aerosols, eye/ear preparations or other formulations where it is
likely that each unit of product (for example, syringe, single dose pipettes) will be dispensed for
the treatment of an individual animal, the number of individual units sold should be considered
equivalent to the number of animals treated.
• For the majority of pharmaceutical veterinary medicinal products, the number of animals treated
will be a function of:
Recommended treatment regimen (daily RTD (mg/kg) x duration of treatment (days)), as
detailed on the authorised SPC. Where a range for dose or duration of therapy is indicated on
the SPC, it is appropriate to calculate incidence based on a ‘worst case’ scenario (that is, use

Public EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 Page 16/28

 the upper limit of the dose range and/or duration of therapy). Following from the worst case
calculation, it is acceptable to propose alternative assessments of incidence based on known
conditions of use of the product. Any such alternative calculations should be justified.
Average weight of target population (kg).8
Amount of product sold
• For immunological veterinary medicinal products, the number of animals treated may be
considered equivalent to the total number of doses sold. Any calculations relating to lack of
expected efficacy should take into account the recommended treatment regimen (initial course
plus booster doses).

A proportion of veterinary medicines are indicated for more than one target animal species. Where this
situation pertains it is recognised that it is difficult to calculate individual species incidence of adverse
reactions. However, it is suggested that the ratio be computed for each species based on the estimated
conditions of use of the product (sales/species). This information is of importance to competent
authorities although the arbitrary nature of such theoretical calculation is recognised.

A number of PSURs will show no reports of adverse reactions. In these cases it is not possible to
calculate any incidence of adverse reactions.

6.3.5 Reports from other sources

A narrative overview of available data from other sources (e.g. post authorisation studies, published
adverse reaction reports) should be included in this section. Where appropriate, the MAH should
cross-refer to available safety information concerning related products (for example, for single active
products it would be considered appropriate to cross-refer to available safety information on a
combination product containing the same active substance(s).

Published reports relating to adverse reactions or other relevant safety information should be included
as an appendix (Appendix II).

6.3.6 Overall safety evaluation

The PSUR should include a concise critical analysis and opinion on the risk/benefit profile of the
product written by a suitably qualified expert for pharmacovigilance. This section should include:
• information on any previous action taken by either regulatory authorities or the MAH as a result
of safety issues, and
• any new important information on the following:
i) evidence of previously unidentified toxicity
ii) increased frequency of known toxicity
iii) drug interactions
iv) overdose and its treatment
v) adverse reactions associated with off-label use.
vi) adverse reactions in humans related to the use of the product.

For each of these points, lack of significant information should be reported.

8 The following ‘standard’ weights are proposed: horse – 550 kg; dog – 20 kg; cat – 5 kg; cow – 550 kg; beef
calf – 150 kg; newborn calf – 50 kg; sow/boar – 160 kg; finishing pig – 60 kg; weaner – 25 kg; sheep – 60 kg;
lamb – 10 kg. For other species, the weight used in the calculation should be justified.

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The evaluation should indicate in particular whether the safety data remain in line with the cumulative
experience to date and the SPC, and should specify any action recommended and the reasons why.

6.3.7 Important information received after data lock point

This section is for reporting any important new information received by the MAH since the database
was frozen for review. It may include significant new cases or follow-up data that affect the
interpretation or evaluation of existing reports. The impact of this information on the overall safety
evaluation should be discussed.

MAH are reminded that data relating to serious adverse reactions must also be reported to the relevant
Competent Authority as expedited reports, see section 5.3.

6.3.8 Individual case histories (PSUR line listings)

The minimum information constituting a reportable individual case is listed at section 4.2.

The individual case histories of all reports (A, B, O and N coded reports) should be presented as a line
listing. The line listing should be included as an appendix to the PSUR. It will be necessary, in a given
report, to separate data relating to different formulations (dosage form(s) and strength(s)). Within
formulation, the safety data should be further differentiated based on target species (if the veterinary
medicinal product is authorised for use in more than one species), reaction type (that is, serious, non-
serious, human reaction, etc.), and then country where the report originated.

For adverse reactions in animals, the standard information required in the PSUR, for an individual
case includes:
i) MAH case reference number (+ country where adverse reaction occurred if the PSUR relates
to more than one country)
ii) Competent Authority case reference number, if relevant
iii) Date(s) of treatment(s)/Date(s) of vaccination(s)
iv) Was the product used as recommended?
v) Date of reaction
iv) Number of animals treated
vii) Species
viii) Age(s)
ix) Number reacted (approximate)
x) Number dead
xi) Other products, including authorised medicated premixes, used concurrently (Trade name and
active substances)
xii) Presenting signs/diagnosis (to include VEDDRA terminology), including timing and duration
xiii) MA comments – brief, informative narrative
xiv) Causality assessment (A, B, O, N code)

All the individual case information listed above should be presented in the line-listing format given in
Table B(1).

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For adverse reactions in humans involving veterinary medicinal product, the standard information
required in the PSUR, for an individual case includes:
i) MAH case reference number (+ country where incident reaction occurred if the PSUR relates
to more than one country)
ii) Competent Authority case reference number, if relevant
iii) Date(s) of exposure
iv) Date(s) of reaction
v) Name(s) and region of address (for cross-reference to avoid duplication)
vi) Occupation
vii) Nature of accident/exposure
viii) Nature of reaction/symptoms
ix) Outcome of reaction) and medical consultation, if applicable
x) MAH comments – brief, informative narrative

Case information relating to adverse reactions to humans involving veterinary medicines should be
presented in the format given in Table B(2).

6.5 Content of Periodic Safety Update Reports – Non-marketed products

For authorised veterinary medicinal products that are not marketed or distributed anywhere and for
which no adverse reactions (either in animals of humans) were observed in any additional trial (e.g.
clinical trial, post authorisation study) abridged PSURs are considered sufficient, which must contain
the following elements only:
• trade name of the product
• marketing authorisation number(s) of the product,
• name and address of the MAH,
• a declaration of the MAH’s Qualified Person for pharmacovigilance, that as the veterinary
medicinal product was not marketed or distributed anywhere in the world during the reporting
period and as no adverse reaction (either in animals or in humans) was observed in any
additional trial (e.g. clinical trial, post authorisation study), the risk/benefit balance afforded
by the veterinary medicinal product has not changed since the date of the Marketing
Authorisation.

6.6 Urgent Safety Information

In accordance with Article 27(3) of Directive 2001/82/EC, any new or changing information that
becomes available which impacts on, or may influence the overall benefit/risk evaluation of a
veterinary medicinal product, should be communicated to all relevant competent authorities by the
MAH immediately upon receipt. A comprehensive report evaluating the issue and the risks in the
context of the benefits should be submitted at the earliest opportunity to all relevant competent
authorities.

7. HUMAN REACTIONS TO VETERINARY MEDICINAL PRODUCTS

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Information about any adverse reactions (serious or non-serious) in humans, as a result of
administering or exposure to veterinary medicinal products, should be given with the following
details:
i) Patient identification (as appropriate according to national laws). A name or unique identifier
shall be given to allow further information to be requested/collected and to avoid any
duplication of reports
ii) Sex
iii) Age, date of birth or adult/child
iv) Occupation - if relevant to exposure to product for example: veterinary surgeon, farm worker,
pet owner
v) Date product used or date exposed to veterinary medicinal product(s)
vi) Date of reaction
vii) Nature of exposure (Details of type of exposure e.g. inhalation, injection, ingestion or dermal,
how much exposure occurred e.g. volume injected or splashed etc and how it occurred e.g.
was it an accident or routine use? And how long did the exposure last (duration). See also xiv)
below for details of animals being treated.)
viii) Nature of reaction including signs and symptoms
ix) Outcome of reaction (e.g. extent of recovery, specific treatment required)
x) Name, address, telephone number of medical doctor/physician (or Poison Centre) if consulted
xi) Marketing Authorisation conclusions/comments on the adverse reaction

Additional information to be provided on the report form to the competent authority:

xii) Status (e.g. veterinarian, pharmacist, other…); name and contact details of the person who
reported the reaction to the MAH, if other than the patient, and if acceptable under national
law for follow-up /further information
xiv) If relevant to incident: Animal data (e.g. way of administration, administration site, number of
animals being treated, species and breed)
xv) Product details: trade name, MA number, active substance and ATCvet code(s). This should
be provided for each of the veterinary medicines that the ‘patient’ has been exposed to in this
incident

Any other information on human adverse reactions to veterinary medicinal products available to the
MAH should be reported if relevant to the case.

All adverse reactions in humans, to veterinary medicinal products, authorised nationally, mutually
recognised or centrally should be reported immediately, and in no case later than 15 days following
receipt, to the competent authorities of the Member State in whose territory the incident occurred.
Where not all the information is available at the time of sending the report the minimum information
may be sent (see section 4.2) with a follow-up report to be sent later.

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 ANNEX I

Event Chart of Industry Reporting Procedures

Serious Adverse Reactions in ANIMALS to Veterinary Medicinal Products

Where the serious Unexpected/

Type of Authorisation Where to report When to report
SAR occurred Expected
National including Unexpected and To MS where the reaction occurred Within 15 days of receipt
mutual recognition Expected To MS(s) where the product is authorised In the relevant PSUR
Unexpected and To MS where the reaction occurred Within 15 days of receipt
Community
Expected To EMEA and all MS In the relevant PSUR
In EU • Mutual recognition
• Products considered In addition to reporting within 15 days
In addition to reporting to the MS where the reaction
within the scope of and in the PSUR, submit reports at
Unexpected and occurred, ensure that serious SARs are reported in such a
Directive 87/22/EEC intervals and in format to be agreed
Expected way as to be accessible by the Reference Member State
(ex-concertation) with RMS or a competent authority
(RMS) or a competent authority designated as RMS
• Products that have been designated as RMS
subject to a referral
To EMEA and MS where the product is authorised Within 15 days of receipt
National including Unexpected
mutual recognition To MS(s) where the product is authorised In the relevant PSUR

Outside EU Expected To MS(s) where the product is authorised In the relevant PSUR
Within 15 days of receipt and later in
Unexpected To EMEA and to all MS
Community the relevant PSUR
Expected To EMEA and to all MS In the relevant PSUR

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 Event Chart of Industry Reporting Procedures

Non-Serious Adverse Reactions in ANIMALS to Veterinary Medicinal Products

Where the SAR Type of Unexpected/

Where to report When to report
occurred Authorisation Expected

National including Unexpected and

To MS(s) where authorised In the relevant PSUR
mutual recognition Expected
In EU
Unexpected and
Community To EMEA and to all MS In the relevant PSUR
Expected

National including Unexpected and

To MS(s) where authorised In the relevant PSUR
mutual recognition Expected
Outside EU
In the relevant PSUR in a distinct
Unexpected To EMEA and to all MS
Community and clearly identified section

Expected To EMEA and to all MS In the relevant PSUR

Public EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 22/28

 Event Chart of Industry Reporting Procedures
Adverse Reactions in HUMANS to Veterinary Medicinal Products

Where the Unexpected/

Type of Authorisation Where to report When to report
SAR occurred Expected
National including mutual Unexpected and To MS where the reaction occurred Within 15 days of receipt
recognition Expected To MS(s) where the product is authorised In the relevant PSUR
Unexpected and To MS where the reaction occurred Within 15 days of receipt
Community*
Expected To EMEA and all MS In the relevant PSUR
In EU
• Mutual recognition
In addition to reporting to the MS where the In addition to reporting within 15 days
• Products considered within
reaction occurred, ensure that serious SARs are and in the PSUR, submit reports at
the scope of Directive Unexpected and
reported in such a way as to be accessible by the intervals and in format to be agreed with
87/22/EEC (ex-concertation) Expected
Reference Member State (RMS) or a competent RMS or a competent authority designated
• Products that have been authority designated as RMS as RMS
subject to a referral
To EMEA and MS(s) where the product is
National including mutual Unexpected and Within 15 days of receipt
authorised
recognition Expected
Outside EU To MS(s) where the product is authorised In the relevant PSUR
Unexpected and Within 15 days of receipt and later in the
Community* To EMEA and to all MS
Expected relevant PSUR

* Directive 2001/82/EC specifically lays down requirements for the reporting of adverse reactions in human beings, which apply to nationally authorised and mutually recognised
veterinary medicinal products. The more dated Council Regulation (EEC) No 2309/93 does not yet make a distinction between adverse reactions to veterinary medicines in
human beings and in animals. However the guidance drafted in accordance with Article 46 of this Regulation defines that all adverse reactions in human beings should be
reported within 15 days (see sections 2.1.1 and 7 of this guideline) in addition to the required reporting in the relevant PSUR.

Public EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 23/28

 TABLE A
European Veterinary Pharmacovigilance Reporting Form for MAHs
Safety issues SENDER REPORT IDENTIFICATION – CASE REF. No: 1
in animals
in humans Reporting country:
Off label use
Lack of expected efficacy Purchase country:
Withdrawal period issues Report source:
Environmental problems
2.
1. NAME ANDOF
ADDRESS ADDRESS OF SENDER
COMPETENT AUTHORITY

Date complaint received by sender:

(dd/mm/yy)
Type of report: Initial Follow-up (date, case number)
Person who reported the reaction: veterinarian owner physician pharmacist other:
3. VETERINARIAN / PHYSICIAN / PHARMACIST 4. ANIMAL OWNER / HUMAN PATIENT
Name: Name (according to the confidentiality legislation in EU country):

Address: Address:

Telephone No. Telephone No.

5. ANIMAL DATA No. of animals treated: No. of animals showing signs: No. of animals died:

Animal characteristics (animal(s) showing signs):

Species: Breed/production type:
Sex/physiological status: female male pregnant neutered lactating other:
Weight (kilos): Age:
State of health at time of treatment: good fair poor critical unknown
Reason(s) for treatment (prevention against what disease(s) or initial diagnosis):

6. PRODUCT DATA # 1
Trade name (include dosage form and strength): M.A. number:

Active substance(s) (INN): ATC vet code(s):

Batch No.: Expiry date: Storage details:

Treatment details:
Dose/frequency: Route/site of administration:

Start date of treatment: Stop date or duration: Who administered the product:
veterinarian owner other
Use according to label: yes unknown no explain:

Action taken after reaction: drug withdrawn dose reduced other

Did reaction abate after stopping drug ? yes no not applicable

Did reaction reappear after reintroduction ? yes no not applicable
List all other relevant medications given to animal(s):
Give the list of the other veterinary medicinal products used concurrently and go to special field for
completion of details (page 3)

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 SENDER CASE REF. No: 2

7. REACTION DATA (applicable for all types of adverse reaction(s) Date of onset of signs:
reported following administration of veterinary product(s) Duration of reaction:
Describe the sequence or events including administration of product(s), all clinical signs, site of reaction, severity, pertinent lab
tests, necropsy results, possible contributing factors (if necessary use extra sheet): Include details of treatment given to address
this adverse reaction.

Were the signs treated?

No Yes

Outcome of reaction to date:

Killed/euthanised died under treatment alive with sequalae recovered unknown
No. of animals:
Date when:

8. ATTENDING VETERINARIAN’S LEVEL OF SUSPICION THAT PRODUCT #1 CAUSED REACTION

possible unlikely no attending vet

9. PREVIOUS EXPOSURE AND REACTION(S) TO PRODUCT #1

Previous exposure to this product? no yes Date(s):

Previous reaction to this product? no yes Describe:
De-challenge information:

10 DETAILS OF SUSPECTED ADVERSE REACTION(S) IN HUMANS

10.

Patient details Sex: Age/date of birth: Occupation (with relevance to exposure):

Date of exposure: Date of reaction:

Nature and duration of exposure, reaction details (including symptoms) and outcome:

11. CAUSALITY ASSESSMENT RELATED TO PRODUCT #1

Classification: A (probable) B (possible) O (unclassified) N (unlikely)

Reason for classification:

12. OVERALL CAUSALITY ASSESSMENT RELATED TO ALL SUSPECTED PRODUCTS

FOR COMPETENT AUTHORITY USE ONLY

Name and title of person responsible for the accuracy of the information Signature Date

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To replicate for each product used concurrently SENDER CASE REF. No: 3

6. DATA FOR PRODUCTS ADMINISTERED CONCURRENTLY – PRODUCT # <Enter sequential number; 2 or higher>

Trade name (include dosage form and strength): M.A. number:

Active substance(s) (INN):: ATC vet code(s):

Batch No.: Expiry date: Storage details:
Treatment details:
Dose/frequency: Route/site of administration:

Start date of treatment: Stop date or duration: Who administered the product:
veterinarian owner other
Use according to label: yes unknown no explain:

Action taken after reaction: drug withdrawn dose reduced other

Did reaction abate after stopping drug? yes no not applicable

Did reaction reappear after reintroduction? yes no not applicable

8. ATTENDING VETERINARIAN’S LEVEL OF SUSPICION THAT REACTION WAS CAUSED BY PRODUCT #

possible unlikely no attending vet

9. PREVIOUS EXPOSURE AND REACTION(S) TO PRODUCT #

Previous exposure to this product? no yes Date(s):

Previous reaction to this product? no yes Describe:
De-challenge information:

11. CAUSALITY ASSESSMENT RELATED TO PRODUCT #

Classification: A (probable) B (possible) O (unclassified) N (unlikely)

Reason for classification:

Pubic EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 26/28

 TABLE B(1)
IN CONFIDENCE

VETERINARY PHARMACOVIGILANCE SCHEME - PERIODIC SAFETY UPDATE REPORT

MARKETING AUTHORISATION HOLDER FORM FOR REPORTS OF ANIMAL ADVERSE REACTIONS
TO A VETERINARY MEDICINAL PRODUCT

MARKETING AUTHORISATION HOLDER:

PRODUCT: MARKETING AUTHORISATION NO:
PERIOD OF REPORT FROM .../.../... TO .../.../.... NO. OF DOSES SOLD IN THE EU DURING PERIOD OF REPORT= DOSE UNITS = % INCIDENCE =

MAH CA CASE DATE OF DATE OF NO. SPECIES NO. NO. WAS PRODUCT OTHER PRESENTING MAH ABON
CASE REF REF TREATMENT/ REACTION TREATED AND AGE REACTED DIED USED AS PRODUCTS USED SIGNS/ CONCLUSIONS CODE
VACCINATION (Juv/Adult) (a) (b) RECOMMENDED CONCURRENTLY DIAGNOSIS AND
YES/NO COMMENTS
EU (Please
REPORTS ensure that
this total is
(REF + put in) (Please ensure these
NAME & sections are completed)
COUNTRY)

OVERALL TOTAL OF ALL (EU) PAGES

Total no of (reports): Total no of animal reactions (a): Total no of animals died (b):
THIRD
COUNTRY
REPORTS

(REF +
COUNTRY)
OVERALL TOTAL OF ALL (3rd Country) PAGES
Total no of incidents (reports): Total no of animal reactions (a): Total no of animals died (b):

FOR COMPETENT AUTHORITY USE ONLY: REFERENCE: DATE OF RECEIPT:

Public EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 27/28

 TABLE B(2)
IN CONFIDENCE

VETERINARY PHARMACOVIGILANCE SCHEME – PERIODIC SAFETY UPDATE REPORT

MARKETING AUTHORISATION HOLDER FORM FOR REPORTS OF ADVERSE REACTIONS IN HUMANS INVOLVING A
VETERINARY MEDICINAL PRODUCT
MARKETING AUTHORISATION HOLDER
PRODUCT: MARKETING AUTHORISATION NO:
PERIOD OF REPORT FROM -----/-----/----- TO -----/-----/-----
MAH CASE CA CASE NAME(S) + REGION OF OCCUPATION DATE OF DATE OF NATURE OF NATURE OF DOCTOR MAH CONCLUSIONS AND
REF REF ADDRESS OF EXPOSURE REACTION ACCIDENT/ REACTION/ SYMPTOMS CONSULTED? & COMMENTS
‘PATIENT’/PERSON EXPOSURE OUTCOME OF
AFFECTED REACTION

(REF +
NAME &
COUNTRY)

FOR COMPETENT AUTHORITY USE ONLY

REFERENCE: DATE OF RECEIPT: NUMBER OF INCIDENTS:

Public EMEA/CVMP/183/96- Rev.1-CONSULTATION EMEA 2004 28/28