Contains Non-Binding Recommendations 

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117 

Guidance for Industry 

Pharmacovigilance of Veterinary Medicinal Products: 

Management of Adverse Event Reports (AER's) - 

VICH GL24 

DRAFT GUIDANCE 

This guidance document is being distributed for comments only 

This draft guidance document describes a system for the management of adverse drug event reports 

following the use of marketed veterinary medicinal products. 

Comments and suggestions regarding the document should be submitted to Division of Dockets 

Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 

20852. Submit electronic comments to http://www.regulations.gov. All comments should be identified 

with the Docket No. 2000D-1632. 

For further information regarding this document, contact Margarita Brown, Center for Veterinary 

Medicine, (HFV-240), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 

240-276-9048, e-mail: margarita.brown@fda.hhs.gov.

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Veterinary Medicine 

May 1, 2006
Contains Non-Binding Recommendations 

Draft—Not for Implementation 

 VICH GL 24 (PHARMACOVIGILANCE) 

November 2005 

For consultation at Step 4 

PHARMACOVIGILANCE OF VETERINARY MEDICINAL 

PRODUCTS – MANAGEMENT OF ADVERSE EVENT 

REPORTS 

Recommended for Consultation 

at Step 4 of the VICH Process 

on 2 November 2005 

by the VICH Steering Committee

This Guidance has been developed by the appropriate VICH Expert Working Group and is subject 

to consultation by the parties, in accordance with the VICH Process. At Step 7 of the Process the 

final draft will be recommended for adoption to the regulatory bodies of the 

European Union, Japan and USA. 

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PHARMACOVIGILANCE OF VETERINARY MEDICINAL PRODUCTS

Management of Adverse Event Reports 

I. Introduction ...............................................................................................................4 

II. Scope ..........................................................................................................................5 

III. Definitions..................................................................................................................6 

III.1 Veterinary Medicinal Product (VMP)...........................................................................6 

III.2 Adverse Event (AE)....................................................................................................6 

III.3 Serious Adverse Event ................................................................................................6 

III.4 Unexpected Adverse Event..........................................................................................7 

III.5 Adverse Event Report (AER).......................................................................................7 

III.6 Marketing Authorization Holder (MAH).......................................................................7 

III.7 Regulatory Authority (RA)..........................................................................................7 

III.8 Periodic Summary Update (PSU).................................................................................7 

III. 9 International Birth Date..............................................................................................7 

IV. The Pharmacovigilance Process....................................................................................7 

IV.1 Information Flow in the Pharmacovigilance System.......................................................8 

IV.2 Informational Unit .....................................................................................................8 

IV.3 Recording AERs ........................................................................................................8 

IV.4 Submitting AERs .......................................................................................................8 

IV.5 Expedited AER Submissions.......................................................................................8 

IV.6 Periodic AER Submissions.........................................................................................9 

IV.7 Reporting Source.......................................................................................................9 

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This draft guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s) 

current thinking on this topic. It does not create or confer any rights for or on any person and does not 

operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the 

requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, 

contact the FDA staff responsible for implementing this guidance. If you cannot identify the 

appropriate FDA staff, call the appropriate number listed on the title page of this guidance. 

I. 

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Introduction 

Pharmacovigilance of veterinary medicinal products (VMPs) can be defined as the detection and 

investigation of the effects of the use of these products, mainly aimed at safety and efficacy in animals and 

safety in people exposed to the products. This document will only deal with the spontaneous reporting 

system for identification of possible adverse events following the use of marketed VMPs. 

Within all regions involved in the VICH process there are certain legal obligations for the pharmaceutical 

industry, the commercial party responsible for the products, with regard to adverse events reported to them. 

Those legal obligations relate to the acceptance of adverse event reports and the storage and submission of 

those reports to the authorities. 

It is of importance for all parties, the Marketing Authorization Holders (MAHs), the Regulatory Authorities 

(RA) and the users of VMPs to develop harmonized and common systems, common definitions and 

standardized terminology within pharmacovigilance. Harmonization of those elements between the regions 

facilitates the reporting responsibilities for the MAHs, many with worldwide activities. At the same time 

harmonization of systems and requirements facilitates the inter-regional comparison of data and exchange of 

information, thereby increasing the general knowledge of a product`s general performance and safety 

profile. 

FDA’s guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and 

should be viewed only as recommendations, unless specific regulatory or statutory 

requirements are cited. The use of the word “should” in Agency guidances means that 

something is suggested or recommended, but not required.*

II. Scope 

The scope of pharmacovigilance in this VICH document is defined as the management of the detection and 

investigation of the clinical effects of marketed VMPs mainly concerned with the safety and efficacy in 

animals and the safety in people exposed to these products. While pharmacovigilance in its broadest sense 

may entail a wide range of activities, this document only deals with the spontaneous reporting system for the 

identification of possible adverse events following the use of marketed VMPs. 

* Under 21 CFR 10.115(i)(3), when issuing draft guidance documents that are the product of international 

negotiations, FDA need not apply 21 CFR 10.115(i)(2), which states that guidance documents must not include 

mandatory language such as "shall," "must," "required," or "requirement," unless FDA is using these words to describe 

a statutory or regulatory requirement. However, any final guidance document issued according to 21 CFR 10.115(i) 

must contain the elements in 21 CFR 10.115(i)(2). In this draft guidance, any language that is mandatory under U.S. 

laws and/or regulations is followed by a citation to the appropriate statutory or regulatory provision. In accordance 

with 21 CFR 10.115(i)(3), any mandatory language in this draft guidance that does not describe a statutory or 

regulatory requirement will be revised in the final guidance document to comply with 21 CFR 10.115(i)(2). 

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III. Definitions 

The terms and definitions in this document are intended to harmonize other previously used terms referring 

to similar concepts. Within the scope of this document the following definitions of items or actions have 

been developed. 

III.1 Veterinary Medicinal Product (VMP) 

Any medicinal product with approved claim(s) to having a protective, therapeutic or diagnostic effect or 

to alter physiological functions when administered to or applied to an animal. The term applies to 

therapeutics, biologicals, diagnostics and modifiers of physiological function. (For the definitions of 

"drug" and "new animal drug" in the U.S., see 21 U.S.C. 321(g)(1) and (v).) 

The “same biological VMP” is defined as originating from the same MAH being responsible for 

pharmacovigilance of this/these VMPs with same manufacturing specifications. 

 

The “same pharmaceutical VMP” is defined as originating from the same MAH being responsible for 

pharmacovigilance of this/these VMPs with same formulations. 

A “similar pharmaceutical VMP” is defined as: 

• originating from the same MAH being responsible for pharmacovigilance of this/these VMPs, 

• the same active ingredients, 

•major excipients with the same or similar pharmaceutical function, 

• at least one common registered species. 

III.2 Adverse Event (AE) 

An adverse event is any observation in animals, whether or not considered to be product-related, that is 

unfavorable and unintended and that occurs after any use of VMP (off-label and on-label uses). 

Included are events related to a suspected lack of expected efficacy according to approved labeling or 

noxious reactions in humans after being exposed to VMP(s). (See 21 C.F.R. 514.3 for the definition of 

an adverse drug experience in the U.S.) 

An AE may at some point be concluded by a RA to be an adverse reaction when there is at least a 

reasonable possibility (i.e., relationship cannot be ruled out) that harmful and unintended observations 

were a response to a VMP administered at doses normally used in animals for prophylaxis, diagnosis or 

therapy of disease or for modification of physiological function. 

III.3 Serious 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. (See 21 C.F.R. 

514.3 for the definition of a serious adverse drug experience in the U.S.) 

For animals managed and treated 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. 

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III.4 Unexpected Adverse Event 

An unexpected adverse event is an adverse event of which the nature, severity or outcome is not 

consistent with approved labeling or approved documents describing expected adverse events for a 

VMP. (See 21 C.F.R. 514.3 for the definition of an unexpected adverse drug experience in the U.S.) 

III.5 Adverse Event Report (AER) 

An adverse event report is a direct communication from an identifiable first-hand reporter (see IV.7) 

that includes at least the following information: 

• an identifiable reporter 

• an identifiable animal(s) or human(s) 

• an identifiable VMP 

• one or more adverse events 

One animal or one human being, or a medically appropriate group exhibiting similar clinical signs 

should be included in a single report. 

III.6 Marketing Authorization Holder (MAH) 

The Marketing Authorization Holder is the commercial party who, according to the RA is responsible 

for the pharmacovigilance of the VMP. (See 21 CFR 514.80 for requirements on establishing, 

maintaining, and reporting required information relating to experiences with a new animal drug, 

defined in 21 U.S.C 321(v).) 

III.7 Regulatory Authority (RA) 

The Regulatory Authority is the national or regional authority which, according to the legislation, is 

responsible for the issuing, adaptation or withdrawal of marketing authorizations/licences of VMPs and 

for pharmacovigilance activities. (See 21 U.S.C 360b.) 

III.8 Periodic Summary Update (PSU) 

The document submitted to the RA at set intervals to support the continued marketing and the adequacy 

of the approved labeling of the VMP and will include an analysis of all AERs received during the 

interval. (See 21 C.F.R. 514.80 for periodic drug experience report requirements in the U.S.) 

III.9 International Birth Date 

International Birth Date (IBD) is the date of the first marketing authorization for same or similar product 

granted in any VICH region. 

IV. The Pharmacovigilance Process 

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, where the reporter communicates with the RA and the RA notifies the MAH of AERs it has 

n the pharmacovigilance system covered by this document is the AER. 

 nor implies any 

.R. 514.80 for recordkeeping requirements in the U.S. 

ent or agreement with 

ons require differently.

IV.1 Information Flow in the Pharmacovigilance System. 

The flow of information is illustrated below: 

 

Information Flow in the Pharmacovigilance System. 

Data preferably flows as shown in the upper half of the figure, where the reporter communicates with 

the MAH and the MAH submits AERs it has received to the RA. An alternate path is shown in the 

lower half

received. 

IV.2 Informational Unit 

The basic unit of information i

IV.3 Recording AERs 

The MAH should record each AER received and store it in a manner which allows easy access to the 

data. The receipt, acknowledgement or recording of an AER by the MAH or the RA does not 

necessarily have any implication regarding the veracity or authenticity of the AER

degree of causality. See 21 C.F

IV.4 Submitting AERs 

The MAH must submit an AER to regional authorities as provided by relevant laws or legislation either 

as an expedited submission or as a periodic submission. See 21 C.F.R. 514.80 for reporting 

requirements. The submission of an AER does not necessarily imply an endorsem

its content, unless regional or national regulati

IV.5 Expedited AER Submissions 

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xpedited submission of certain AERs may be required (see 21 CFR 514.80), related to the seriousness 

regarding the 

afety of animals or man. 

r when: 

 where the AER occurs and 

rver countries and 

• the species of animal involved in the AER is a species approved in the other VICH 

lock for the expedited submission to RAs in other VICH regions/observer countries begins 

when the AER becomes the knowledge of the MAH within the other region. A follow-up submission 

, based on these expedited submissions, the RA decides on a regulatory action, the MAH will 

In addition, when the MAH determines that it is likely that actions will be implemented based on the 

AERs it has received, the MAH will contact all VICH regions/observer RAs where the same VMP is 

rns and its likely actions. 

t regular intervals, the MAH must submit all AERs not previously submitted. See 21 C.F.R. 514.80 

ort requirements in the U.S. 

AH, but the AER may also have been routed through an agent or the RA. A 

communication through an intermediate agent should be considered an AER only if the agent has been 

authorized by the reporter and provides sufficient information to allow direct contact between the 

reporter and the MAH.

E

or unexpectedness of the reported event or because of the urgency of its implications 

s

Expedited submission to RAs in other VICH regions/observer countries will occu

• an AER is an expedited submission in the country

• the same VMP is approved in other VICH regions/obse

regions/observer countries or 

• there are serious implications regarding human safety 

The timec

will occur when the investigation of the AER is completed by the MAH in the country where the AER 

occurred. 

If

immediately inform all VICH regions/observer country RAs where the same VMP is approved about 

this action. 

approved to inform them of the MAH conce

IV.6 Periodic AER Submissions 

A

for periodic drug experience rep

IV.7 Reporting Source 

Although reporting via the attending veterinarian is encouraged, an AER may be initiated by anyone 

directly involved with the purported adverse event. Preferably, an AER is communicated by the 

reporter directly to the M