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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DRAFT GUIDANCE 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This draft guidance document describes a system for the management of adverse drug event reports 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 
DraftNot for Implementation 
 
     VICH GL 24 (PHARMACOVIGILANCE) 
November 2005 
For consultation at Step 4  
 
 
 
 
 
 
P V M
HARMACOVIGILANCE OF  ETERINARY  EDICINAL 
P  M A E
RODUCTS    ANAGEMENT OF  DVERSE  VENT 
R  
EPORTS
 
 
 
 
 
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 Administrations (FDAs) 
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.  
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys 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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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, where the reporter communicates with the RA and the RA notifies the MAH of AERs it has 
received. 
IV.2  Informational Unit 
 
The basic unit of information in the pharmacovigilance system covered by this document is the AER. 
 
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 nor implies any 
degree of causality.  See 21 C.F.R. 514.80 for recordkeeping requirements in the U.S. 
 
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 endorsement or agreement with 
its content, unless regional or national regulations require differently. 
 
IV.5  Expedited AER Submissions 
 
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Expedited submission of certain AERs may be required (see 21 CFR 514.80), related to the seriousness 
or unexpectedness of the reported event or because of the urgency of its implications regarding the 
safety of animals or man. 
 
Expedited submission to RAs in other VICH regions/observer countries will occur when: 
 
 an AER is an expedited submission in the country where the AER occurs and 
 the same VMP is approved in other VICH regions/observer countries and  
 the  species  of  animal  involved  in  the  AER  is  a  species  approved  in  the  other  VICH 
regions/observer countries or 
 there are serious implications regarding human safety  
 
The timeclock 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 
will occur when the investigation of the AER is completed by the MAH in the country where the AER 
occurred. 
 
If, based on these expedited submissions, the RA decides on a regulatory action, the MAH will 
immediately inform all VICH regions/observer country RAs where the same VMP is approved about 
this action.   
 
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 
approved to inform them of the MAH concerns and its likely actions. 
 
IV.6  Periodic AER Submissions 
 
At regular intervals, the MAH must submit all AERs not previously submitted.  See 21 C.F.R. 514.80 
for periodic drug experience report requirements in the U.S. 
 
 
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 MAH, 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. 
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