104 
Guidance for Industry 
 
Content and Format of Effectiveness and Target Animal Safety 
 Technical Sections and Final Study Reports For Submission to the 
Division of Therapeutic Drugs for Non-Food Animals 
 
 
This guidance supercedes the guidance of September 1999.  (This document was revised to 
include the disclaimer in the paragraph below and to update the address to submit 
 
 
Guidance #85 entitled "Good Clinical Practices" became final on May 15, 2001.  Until the Center revises 
guidance #104, sponsors should follow the recommendations in guidance #85 when differences among 
the guidances occur.  For questions please contact Herman Schoenemann (HFV-100), Center for 
Veterinary Medicine, Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, (240) 
276-8302, e-mail:  Herman.Schoenemann@fda.hhs.gov 
 
This document is intended to provide guidance on the content and format of technical section submissions 
for effectiveness and target animal safety and final study reports in support of these technical sections.  
This guidance represents the Food and Drug Administrations (FDAs) current thinking on the content 
and format of effectiveness and safety technical sections and final study reports for submission solely to 
the Division of Therapeutic Drugs for Non-Food Animals.  
 
It does not create or confer any rights for or on any person and does not operate to bind FDA or the 
public.  An alternative approach may be used if such approach satisfies the requirements of the applicable 
statute, regulations or both. 
 
Comments and suggestions regarding this document should be submitted to Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD  
20852.   
 
For questions regarding this guidance document contact Amy Omer (HFV-110), Center for Veterinary 
Medicine, Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, (240) 276-8336, 
e-mail: amy.omer@fda.hhs.gov. 
 
    
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
July 10, 2001   Content/Format of Technical Sections & Final Study Reports  Page 1 of 29 
 
Table of Contents
 
 
I. FOREWORD______________________________________________________________________________4 
II.  GLOSSARY _____________________________________________________________________________5 
III.  EFFECTIVENESS_______________________________________________________________________7 
A.  CONTENT AND FORMAT OF THE TECHNICAL SECTION___________________________________________7 
 
1.  Cover letter __________________________________________________________________________7 
 
2.  Table of contents______________________________________________________________________8 
 
3.  Dosage justification and dose-response characterization______________________________________8 
 
4.  Summary of studies providing substantial evidence of effectiveness _____________________________8 
 
5.  Final study reports of studies providing substantial evidence of effectiveness______________________9 
 
6.  All information, other than substantial evidence, pertinent to effectiveness._______________________9 
 
7.  Foreign market experience______________________________________________________________9 
 
8.  Product labeling _____________________________________________________________________10 
 
9.  FOI summary _______________________________________________________________________10 
 
B.  CONTENT AND FORMAT OF AN EFFECTIVENESS FINAL STUDY REPORT _____________________________10 
 
1.  Title page___________________________________________________________________________10 
 
2.  Table of contents_____________________________________________________________________11 
 
3.  Summary___________________________________________________________________________11 
 
4.  Objective(s) _________________________________________________________________________11 
 
5.  Study schedule_______________________________________________________________________11 
 
6.  Study design_________________________________________________________________________11 
 
7.  Study procedures_____________________________________________________________________12 
 
7.1  Investigational new animal drug and control___________________________________________________ 12 
7.2  Investigational animals_____________________________________________________________________ 12 
7.3  Analytical methods ________________________________________________________________________ 13 
7.4  Study facilities ____________________________________________________________________________ 13 
  Content/Format of Technical Sections & Final Study Reports  Page 2 of 29 
7.5  Feed and Water ___________________________________________________________________________ 14 
7.6  Treatment administration___________________________________________________________________ 14 
7.7  Concomitant medications/therapies___________________________________________________________ 14 
7.8  Criteria for animal removal from a study______________________________________________________ 15 
7.9  Necropsy procedures_______________________________________________________________________ 15 
7.10  Animal and drug accountability and disposition _______________________________________________ 15 
 
8.  Study variables/observations____________________________________________________________15 
8.1  Variables measured for evaluating study objectives _____________________________________________ 15 
8.2  Other observations recorded during the study__________________________________________________ 15 
 
9.  Data calculations and statistical methodologies and analyses _________________________________16 
 
10.  Results____________________________________________________________________________16 
 
11.  Conclusions/discussion_______________________________________________________________16 
 
12.  Personnel__________________________________________________________________________17 
 
13.  Reports____________________________________________________________________________17 
 
14.  Accuracy and Completeness Statement __________________________________________________17 
 
15.  Location of specimens, raw data, and the final study report__________________________________17 
 
16.  Appendices_________________________________________________________________________17 
 
IV.  TARGET ANIMAL SAFETY_____________________________________________________________17 
A.  CONTENT AND FORMAT OF THE TECHNICAL SECTION__________________________________________17 
 
1.  Cover letter _________________________________________________________________________17 
 
2.  Table of contents_____________________________________________________________________18 
 
3.  Summary of target animal safety studies__________________________________________________18 
 
4.  Final study reports ___________________________________________________________________19 
 
5.  All other information pertinent to target animal safety_______________________________________19 
 
6.  Foreign market experience_____________________________________________________________20 
 
7.  Product labeling _____________________________________________________________________20 
 
8.  FOI summary _______________________________________________________________________20 
B.  CONTENT AND FORMAT OF A FINAL STUDY REPORT FOR A SAFETY STUDY__________________________20 
 
1.  Title page___________________________________________________________________________20 
 
  Content/Format of Technical Sections & Final Study Reports  Page 3 of 29 
2.  Table of contents_____________________________________________________________________21 
 
3.  Summary___________________________________________________________________________21 
 
4.  Objective(s) _________________________________________________________________________21 
 
5.  Study schedule_______________________________________________________________________21 
 
6.  Study design_________________________________________________________________________21 
6.1  Description of treatment groups/experimental design____________________________________________ 22 
6.2  Method of assignment to treatment group _____________________________________________________ 22 
6.3  Blinding__________________________________________________________________________________ 22 
 
7.  Study procedures_____________________________________________________________________22 
 
7.1  Test and control articles ____________________________________________________________________ 22 
7.2  Investigational animals_____________________________________________________________________ 23 
7.3  Analytical methods ________________________________________________________________________ 24 
7.4  Study facilities ____________________________________________________________________________ 24 
7.5  Feed and Water ___________________________________________________________________________ 24 
7.6  Treatment administration___________________________________________________________________ 25 
7.7  Concomitant medications/therapies___________________________________________________________ 25 
7.8  Criteria for animal removal from a study______________________________________________________ 25 
7.9  Necropsy procedures_______________________________________________________________________ 25 
7.10  Animal and drug accountability and disposition _______________________________________________ 25 
 
8.  Study variables/observations____________________________________________________________25 
8.1  Variables measured for evaluating study objectives _____________________________________________ 26 
8.2  Other observations recorded during the study__________________________________________________ 26 
 
9.  Data calculations and statistical methodologies and analyses _________________________________26 
 
10.  Results____________________________________________________________________________26 
 
11.  Conclusions/discussion_______________________________________________________________27 
 
12.  Personnel__________________________________________________________________________27 
 
13.  Reports____________________________________________________________________________27 
 
14.  QA Statement_______________________________________________________________________27 
 
15.  Location of specimens, raw data, and the final study report__________________________________27 
 
16.  Appendices_________________________________________________________________________28 
  Content/Format of Technical Sections & Final Study Reports  Page 4 of 29 
 
I.  Foreword 
 
This guidance document was prepared to enable sponsors to submit quality data submissions, 
which will allow for a more efficient review by CVM.  The scope of this document is limited to 
submissions to the Division of Therapeutic Drugs for Non-Food Animals (HFV-110). 
 
A complete New Animal Drug Application (NADA) must be composed of all the sections  
identified in 21 CFR 514.1 and as stated on the Form FDA 356V.  In order to facilitate the 
approval of NADAs, CVM now accepts major data submissions for individual sections of an 
NADA (technical sections) under the Investigational New Animal Drug (INAD) file. To the 
extent possible, CVM reviews each technical section independently.  When CVM finds that all 
the sections are complete the sponsor may file an administrative NADA.  This guidance 
document will focus exclusively on the effectiveness and the target animal safety technical 
sections reviewed by the Division of Therapeutic Drugs for Non-Food Animals. 
 
In CVMs efforts to find ways of improving its efficiency, it was discovered that reviewers often 
found it difficult to locate specific elements within a technical section and determine if all 
necessary elements of the technical section were present in the submission.  This document 
addresses that problem and is intended to provide guidance on the suggested content and format 
of technical section submissions.  Adherence to this guidance should assist CVM reviewers in 
locating and reviewing this information.  The information contained in this guidance applies 
whether effectiveness and target animal safety data are submitted as individual technical sections 
under an INAD or collectively as part of a complete NADA.  This document also provides 
guidance on the content and format of a final study report, which is a fundamental component of 
these technical sections. 
 
Other relevant documents (where appropriate, Office of Management and Budget (OMB) 
information control numbers are in parentheses following the title of the document) include: 21 
CFR Part 511  New Animal Drugs for Investigational Use (OMB 0910-0017), 21 CFR Part 514 
 New Animal Drug Applications (OMB 0910-0037), 21 CFR Part 58  Good Laboratory 
Practice for Nonclinical Laboratory Studies (GLPs) (OMB 0910-0119), 21 CFR Part 11  
Electronic Records; Electronic Signatures (OMB 0910-0303), Good Target Animal Study 
Practices: Clinical Investigators and Monitors (May 1997), Target Animal Safety Guidelines for 
New Animal Drugs (June 1989), Protocol Development Guideline for Clinical Effectiveness and 
Target Animal Safety Trials (November 1994), and CVMs Policy and Procedures Manual 
1240.3040.  References in this guidance to regulations in the Code of Federal Regulations are to 
chapter I of title 21, unless otherwise noted.  
 
These documents, or references to them, can be found on the Internet at 
http://fda.gov/FDAgov/AnimalVeterinary/default.htm.  Paper copies can be obtained from 
  Content/Format of Technical Sections & Final Study Reports  Page 5 of 29 
the Communications Staff (HFV-12), Center for Veterinary Medicine, 7519 Standish Place, 
Rockville, MD 20855. 
 
II.  Glossary 
 
Administrative New Animal Drug Application: The NADA submission that is filed for the 
purpose of seeking approval of the new animal drug for the tested claims after CVM has 
issued technical section complete letters for all technical sections. 
 
Adverse Drug Experience (ADE): Any adverse event associated with the use of an 
investigational or approved new animal drug, whether or not considered to be drug related. 
 
Animal Drug Availability Act of 1996 (ADAA): Legislation enacted October 9, 1996, to 
amend the Federal Food Drug and Cosmetic Act.  The purpose of the ADAA is to facilitate 
the approval and marketing of new animal drugs and medicated feeds.  Among other items, 
the ADAA revised the definition of substantial evidence, which is the standard for 
demonstrating effectiveness. 
 
Clinical Study: A single scientific experiment conducted to test at least one scientific 
hypothesis relevant to the proposed claim(s) made for a new animal drug.  
 
Dosage:  Dosage includes the dose or dose range, dosing frequency and dosing duration. 
 
Experimental Phase Completion Date (for clinical studies): The date on which collection 
of all raw data is complete. 
 
Experimental Phase Initiation Date (for clinical studies): The date on which animals are 
first identified with a treatment. 
 
Final Study Report: The comprehensive description of the study written after its 
conclusion. This report includes a description of the objective(s), experimental materials and 
methods, and a presentation and critical scientific evaluation of the results (including 
statistical analyses where appropriate). 
 
Good Laboratory Practices (GLPs): The regulations governing the conduct of nonclinical 
laboratory studies (21 CFR Part 58). 
 
Investigator:  An individual qualified by training and experience that is entrusted with the 
implementation of the study protocol, collecting study data, and the overall conduct of the 
clinical study. 
 
  Content/Format of Technical Sections & Final Study Reports  Page 6 of 29 
Monitor:  An individual qualified by training and experience who represents the sponsor in 
overseeing the investigators implementation of a protocol and progress of the clinical study 
and determines whether the clinical study is conducted in accordance with all applicable 
requirements. 
 
Nonclinical Laboratory Study: In vivo or in vitro experiments in which test articles are 
studied prospectively in test systems under laboratory conditions to determine their safety.  
See 58.3 (d) for a more detailed definition. 
 
Protocol: A document signed and dated by the investigator for clinical studies (or study 
director for GLP studies) and the sponsor, that states the rationale and objectives of the study 
and all methods and conditions under which the study is to be performed and managed.  The 
term protocol includes all protocol amendments. 
 
Protocol Amendment: A change or modification of the protocol, effected prior to the 
implementation of the protocol or the execution of the changed or modified task, that is 
signed and dated by the investigator (or study director) and sponsor and incorporated into the 
protocol.   
 
Protocol Deviation: A departure from the procedures delineated in the protocol, after the 
protocol has been signed by the investigator (or study director) and sponsor. 
 
Raw Data (for clinical studies): Any worksheets, calibration data, records, memoranda and 
notes of original observations and activities of a study that are necessary for the 
reconstruction and evaluation of the study.  Raw data may include, but are not limited to, 
photographic materials, computer printouts, magnetic, electronic or optical media, 
information recorded from automated instruments, and hand recorded datasheets.  Facsimile 
transmissions and transcribed data are not considered raw data.  
 
Raw Data (for GLP studies): See 58.3 (k) for a complete definition.  
 
Report Amendment: Any addition, deletion or correction to the final study report.  A report 
amendment clearly identifies that part of the study report that is being added, deleted or 
corrected and the reasons for the addition, deletion, or correction, and is signed and dated by 
the authors. 
 
Study Director: The individual responsible for the overall conduct of a nonclinical 
laboratory study.   
 
Study Documentation: All records in any form (including documents, magnetic and optical 
records) describing methods and conduct of the study, factors affecting the study, and any 
  Content/Format of Technical Sections & Final Study Reports  Page 7 of 29 
actions taken.  These records include, but are not limited to: protocol, raw data, reports, 
standard operating procedures (SOPs), reference materials, and specimens. 
 
Study Initiation Date: The date the study protocol is signed by the investigator for clinical 
studies or is signed by the study director for GLP studies. 
 
Study Completion Date: The date the final study report is signed by all authors for clinical 
studies or is signed by the study director for GLP studies. 
 
Substantial Evidence: Evidence consisting of one or more adequate and well-controlled 
studies, such as, a study in a target species, a study in laboratory animals, a field 
investigation, a bioequivalence study, or an in vitro study, by experts qualified by scientific 
training and experience to evaluate the effectiveness of the drug involved, on the basis of 
which it could fairly and reasonably be concluded by such experts that the drug will have the 
effect it purports or is represented to have under the conditions of use prescribed, 
recommended, or suggested in the labeling or proposed labeling thereof.  
 
Technical Section: An organizational element of an NADA as defined in 514.1 and 
outlined in the Form FDA 356V.  Each technical section must support a condition of 
approval required by CVM.  All studies supporting a single technical section should be 
submitted as well as other relevant information such as referenced literature, foreign market 
experience, etc.  A technical section should also contain information on the proposed 
conditions of use and/or labeling, and the relevant portion(s) of the FOI Summary. 
 
 
III.  Effectiveness 
   
A.  Content and format of the technical section 
 
1.  Cover letter   
 
The content of the cover letter is administratively used to route the submission to the 
proper review personnel.  Therefore, it is essential to make the purpose of the submission 
explicit in this letter.  The following elements should be included in the cover letter: 
 
  INAD file number 
  Name, address, and telephone number of the sponsor 
  Drug name (include trade name and generic name) 
  Specific purpose of the submission 
  Proposed indications 
  Content/Format of Technical Sections & Final Study Reports  Page 8 of 29 
 
The cover letter and supporting information should be mailed to: Center for Veterinary 
Medicine, Document Control Unit, HFV-199, 7500 Standish Place, Rockville MD 20855. 
 
2.  Table of contents 
 
A general table of contents for the technical section is recommended.  Within a particular 
final study report or volume, a more detailed table of contents is also recommended. 
 
3.  Dosage justification and dose-response characterization 
 
Following the enactment of the ADAA, dosage justification and characterization of 
critical aspects of the dose-response relationship are no longer necessarily part of the 
determination of effectiveness by substantial evidence.  Dosage justification and dose-
response characterization may be supported by several means, including but not limited 
to, dose titration studies, pilot studies or literature (as opposed to dose confirmation).   
Confirmation of the effectiveness of the selected dose or dose range continues to require 
demonstration by substantial evidence.  If a dose range is selected, characterization of the 
dose-response relationship over the dose range selected will generally be needed.  A 
summary of the information used for the justification of dosage and characterization of 
dose-response relationship should be submitted.  Copies of literature and other studies 
should be included. 
 
4.  Summary of studies providing substantial evidence of effectiveness 
 
There are a variety of adequate and well-controlled studies (as defined by 514.117) that 
may be used to support the effectiveness of the new animal drug. The overall summary of 
effectiveness data should generally cover the developmental history of the technical 
section and summaries of all adequate and well-controlled studies.  The developmental 
history is a timeline that describes agreements and discussions between the sponsor and 
CVM and regulatory decisions made by CVM.  A summary of the adequate and well-
controlled studies should include the following information (at a minimum): 
 
  Number and identification of adequate and well-controlled effectiveness studies 
  Type of studies (clinical field, pharmacokinetic, in vitro, etc.) 
  Study Initiation Date, Experimental Phase Initiation/Completion Dates, Study 
Completion Date 
  Number of investigational (treated and control) animals per study 
  Formulation of drug used in each study (e.g., final market formulation, batch number, 
and other pertinent descriptors) 
  Brief description of results for each study 
  Content/Format of Technical Sections & Final Study Reports  Page 9 of 29 
  
A tabular format is suggested as an efficient way to summarize major aspects of studies.  
For example: 
 
Study  Study type:  Study Initiation  Exper. Phase  No. of  Drug 
no.  Effectiveness  & Completion  Initiation &  Animals  Formulation 
Dates  Completion   
Dates 
C030- Clinical field  3/10/95 - 6/10/95  4/11/95-5/11/95  240 adult  final market 
541-98  horses;  formulation 
120 
treated, 
120 
control 
C028- Pharmaco- 1/12/95-4/15/95  2/13/95-3/13/95  20 adult  batch #404 
551-98  kinetic  ponies 
 
More detailed tables may be used to describe effectiveness results.  Although tables are 
preferable, text summaries are also acceptable.  An overall summary of product 
effectiveness should also appear in this section.   
 
 
 
5.  Final study reports of studies providing substantial evidence of effectiveness 
 
The content and format of a final study report is described later in this document.  Each 
study providing substantial evidence of effectiveness should be individually summarized 
in a final study report format with associated appendices.  
 
6.  All information, other than substantial evidence, pertinent to effectiveness.  
 
This section should contain any other information that may be pertinent to evaluating 
effectiveness of the product.  Under 514.1(b)(8)(iv), CVM may refuse an application if 
it does not contain all information pertinent to the evaluation of the safety and 
effectiveness of the new animal drug and related new animal drugs.  Information such as 
reports in the scientific literature, other studies conducted with the product outside the 
U.S., or any evaluations made by the sponsors veterinary consultants or staff should be 
included.  Summaries of this information are acceptable. 
 
7.  Foreign market experience 
 
  Content/Format of Technical Sections & Final Study Reports  Page 10 of 29 
This section includes any adverse drug events (ADEs) or items such as a report on the 
approximate number of units of the product sold outside of the U.S.  Inclusion of the 
foreign approved product package insert (with English translation) is recommended. 
 
8.  Product labeling 
 
Draft product labeling should be submitted at the time the technical section is submitted.  
Emphasis should be placed on sections of product labeling which relate to product 
effectiveness, e.g., indications, dosage and administration, clinical effectiveness, 
cautions, and warnings.  Submission of product labeling on an appropriate electronic 
medium is recommended. 
 
9.  FOI summary 
 
All sections of the FOI (Freedom of Information) summary that pertain to product 
effectiveness should be submitted with the technical section.  Submission of the FOI 
summary information on an appropriate electronic medium is recommended. 
 
B.  Content and format of an effectiveness final study report 
 
One or more adequate and well-controlled studies are required to establish, by substantial 
evidence, that a new animal drug is effective.  The required characteristics of an adequate 
and well-controlled study are described in 514.117(b).  The preparation of a final study 
report (FSR) is a required component of an adequate and well-controlled study.  The FSR 
should be a comprehensive, stand-alone document that provides a clear explanation of the 
study objective(s), experimental materials and methods and a presentation and critical 
scientific evaluation of the results.  The FSR should be written when collection of all raw 
data is complete.  The effectiveness technical section should contain FSRs for each adequate 
and well-controlled study and reports/abstracts of corroborating studies conducted in support 
of a determination of effectiveness. 
 
A study is not considered complete until a FSR is signed by the authors (all individuals 
involved in the preparation of the FSR).  The authors should sign and date and include in the 
FSR a brief statement of their contributions to the FSR.  Any corrections or additions to the 
FSR should be in the form of an amendment by the authors.  The amendment should clearly 
identify that part of the FSR that is being added or corrected and the reason for the correction 
or addition, and should be signed and dated by the authors. 
 
The FSR should contain the following elements:  
 
1.  Title page 
  Content/Format of Technical Sections & Final Study Reports  Page 11 of 29 
 
The title page should contain the following information: 
 
  Title of protocol/study 
  Protocol version and study number (this should also appear on each page of the 
report) 
  Investigational new animal drug generic and trade name 
  Proposed indication(s) 
  Sponsor name and address 
  Investigator(s) name and address 
  Study site(s) name and address 
  Study initiation and completion dates 
  Experimental initiation and completion dates  
  Signature of report author(s), date signed, title of author(s) 
 
 
2.  Table of contents 
 
The table of contents should be comprehensive, identifying each section and subsection 
(and associated page number) of the report.  The insertion of tabs is recommended for the 
principal sections. 
 
3.  Summary 
 
A brief summary of the materials and methods and results of the study should be 
provided. It should describe the critical features of the study, e.g., target population, 
primary parameters, and adverse reactions, and any guidance or regulations that were 
followed during the conduct.  The summary may include text, tables, and graphs. 
 
4.  Objective(s) 
 
A statement under this heading should describe the overall objective(s) of the study as 
stated in the study protocol. 
 
5.  Study schedule 
 
A chronological representation of key events of the study and the dates on which they 
occurred, including the study initiation and completion dates and the experimental 
initiation and completion dates. 
 
6.  Study design 
  Content/Format of Technical Sections & Final Study Reports  Page 12 of 29 
 
The rationale and description of the chosen experimental design of the study should be 
provided.  The number of animals per treatment and a description of each treatment 
should be included.  The nature of the control group should be discussed.  The 
experimental unit should be defined.  An explanation of how the animals were housed 
should be provided.  The randomization procedures, variables used, e.g., weight, gender, 
and age, and statistical programs for randomization should be described completely.  The 
practical arrangements to be followed to allocate animals to treatment groups and 
treatment groups to experimental units should be discussed.  If blinding was appropriate 
to the study design, detail the extent of blinding, how the blinding was accomplished, and 
the circumstances under which the treatment code may be revealed. 
 
 
7.  Study procedures 
 
This section should include all details necessary to reconstruct and understand the 
experimental materials and methods used to conduct the study.  Deviations from the 
protocol should be discussed. 
 
7.1  Investigational new animal drug and control 
 
7.1.1  Description 
 
The description of the investigational new animal drug and control should permit 
an unambiguous determination of the specific formulation.  Characteristics such 
as lot or batch number, trade name, formulation, dosage form, or manufacturing 
site may prove useful. 
 
7.1.2  Storage conditions 
 
The storage conditions of the investigational new animal drug and control during 
the conduct of the study should be described. 
 
7.1.3  Material Safety Data Sheet (MSDS) 
 
The MSDS may be attached as an appendix to this report. 
 
7.2  Investigational animals 
 
7.2.1  Description 
 
  Content/Format of Technical Sections & Final Study Reports  Page 13 of 29 
A complete description of the investigational (control and treated) animals should 
be included.  This description should include, where appropriate, the number of 
treated and control animals, species/breed, age, gender, body weight range, source 
of supply, and procedures used for identification, e.g., neckband and tattoo.  The 
physiological status, e.g., lactating, pregnant, or prepubertal, of the animals 
should also be described. 
 
7.2.2  Owner Consent Forms 
 
The owner consent forms should be attached as an appendix to this report. 
 
 
7.2.3  Inclusion/exclusion criteria 
 
The objective selection criteria used to admit animals to the study should be 
described, including any diagnostic requirements, e.g., physical examination, 
body temperature, or reproductive status.  The rationale for and description of the 
inclusion and exclusion criteria (which prevent an animal from entering the study) 
should be included.  If any animal is used in the study that failed to meet the 
inclusion criteria, the reason should be provided. 
 
7.2.4  Acclimation of investigational animals 
 
An acclimation period allows animals to adapt to the study environment, e.g., 
housing, handling, and feeding practices.  The final study report should describe 
the location of the animals during the acclimation period, the length of the 
acclimation period, any medication(s) and/or vaccines administered during this 
period, and any baseline data collected prior to dose administration. 
 
7.3  Analytical methods 
 
For each analytical method used in the conduct of this study, include, at a minimum, 
a description of the method, a brief methodology (including sample collection, 
preparation and storage; validation; quality control procedures; and supportive 
relevant scientific references), and objective criteria and procedures to assess the 
analytical results.  A certification that all method validations were performed before 
the initiation of the study should be included.  If validations were not performed 
before the start of the study a statement describing the mitigating reasons should be 
included. 
 
7.4  Study facilities 
  Content/Format of Technical Sections & Final Study Reports  Page 14 of 29 
 
7.4.1  Identification and description 
 
The name, address, and complete description of the study facilities should be 
provided.  Such a description could include a general description of the housing 
unit(s) including dimensions of the pertinent areas used during any phase of the 
study.  Diagrams may prove useful to convey this information.   
 
7.4.2  Management procedures 
 
General management procedures, e.g., equipment maintenance and environmental 
control (temperature, humidity, airflow), may have bearing on the study outcome 
and welfare of the animals and should be described.  Where appropriate, the type, 
frequency and duration of exercise provided to the animals should be described. 
 
7.5  Feed and Water 
 
7.5.1  Diets 
 
The diets fed to the investigational animals should meet the nutritional 
requirements of the animals.  When necessary, a qualitative and quantitative 
description of the dietary ingredients should be provided.  The frequency of 
feedings and the quantities of feed offered and refused should be described.  
When the test article is administered in feed, drug feed assays should be 
discussed, especially in terms of proper drug administration.  Discuss differences, 
if any, in the dietary feed intake between the treated and control animals. 
 
7.5.2  Water 
 
The quality and availability of water offered to the animals and water delivery 
systems should be described. 
 
7.6  Treatment administration  
 
A justification for and description of the selected dosage, dosage regimen, route of 
administration, and duration should be included.  Any problems encountered with 
dosing should be discussed as well as observations regarding palatability (if 
applicable). 
 
7.7  Concomitant medications/therapies 
 
  Content/Format of Technical Sections & Final Study Reports  Page 15 of 29 
The type, quantity and duration of concomitant medications/therapies should be 
discussed in this section.  The rationale for use and impact of the 
medications/therapies on the study outcome, e.g., drug interaction or effect on a study 
parameter, should be discussed. 
 
7.8  Criteria for animal removal from a study 
 
It is sometimes necessary to remove an animal from study due to sickness, injury or 
other reasons.  The specific criteria for removal should be detailed as well as the 
procedure for removal and, if appropriate, replacement. 
 
7.9  Necropsy procedures  
 
Details of the gross necropsy performed on dead or moribund animals to determine 
cause of death should be included. 
 
7.10  Animal and drug accountability and disposition 
 
The final disposition of all investigational animals and the investigational new animal 
drug and control article should be described. 
 
8.  Study variables/observations 
 
8.1  Variables measured for evaluating study objectives 
 
Observations include any inspection or examination of investigational animals.  The 
rationale for the variables selected to test the objective of the study should be 
discussed in detail.  In addition, the methods used in assessing the variable should be 
explained or referenced.  The frequency of assessment and the criteria used to 
characterize the measurement of the variable should be stated.  If measurement of a 
variable is derived, the calculations used in the derivation should be provided. 
 
For example, in the evaluation of an anti-inflammatory drug for horses, lameness is 
graded on a scale of 1-5.  The definition of each of the grades should be provided and 
the scale referenced.  In addition, a reason why lameness is an acceptable variable to 
test effectiveness of an anti-inflammatory drug should be provided.  The frequency of 
lameness assessment should be stated and the procedure used to grade the lameness 
discussed. 
 
8.2  Other observations recorded during the study 
 
  Content/Format of Technical Sections & Final Study Reports  Page 16 of 29 
All other types of observations should be discussed such as animal care observations, 
food consumption observations, etc. 
 
9.  Data calculations and statistical methodologies and analyses 
 
A description of all transformations, calculations, or operations performed on the data 
and the statistical methods employed for analyzing the data should be included.  The 
statistical portion of the report is not a printout of the data analysis (which should be 
included as an appendix) but rather, is a description of the data and procedures.  Identify 
the differences that exist, if any, between the data set subjected to statistical analyses and 
the complete raw data.   Define the experimental unit and the number of replicates per 
treatment.  The statistical methodology should be described including the hypotheses 
tested, any estimated parameters or assumptions and any specific statistical model used.  
If any data transformations were performed, a rationale for the choice of transformation 
as well as the impact on treatment effects should be discussed.  Define how the results 
were used to draw conclusions about the study's objective(s) and the appropriateness of 
the choice of statistical method.  Where the actual transformations, calculations, or 
operations performed on the data or the actual statistical methods employed to analyze 
the data differ from that stated in the protocol, a rationale for such deviation should be 
included. 
 
10.  Results 
 
All data collected during the study should be summarized and analyzed.  A description of 
how the results for each protocol-defined parameter support effectiveness should be 
included.  Results should be presented as text, tables or graphs.  The exact location 
(appendix page numbers) of the supporting raw data should be referenced.  Tables and 
graphs should be concise and user-friendly, since individual data will be located in the 
appendices. 
 
11.  Conclusions/discussion 
 
An overall statement of the conclusions drawn from the analysis of the data should be 
included.  The assessment of effectiveness should compare and contrast the effects that 
were to be achieved and the clinical endpoints that were to be reached before 
effectiveness could be claimed with the actual study observations.  Furthermore, a 
description of all circumstances that may have affected the quality or integrity of the data 
should be included.  New or unexpected findings and their impact on the study outcome 
should be identified.  Adverse events and their potential impact and any results, which 
may be inconsistent with the overall study conclusions, should also be discussed in detail. 
 
  Content/Format of Technical Sections & Final Study Reports  Page 17 of 29 
12.  Personnel 
The name of the investigator and other personnel involved in the study should be 
included. 
 
13.  Reports 
 
The signed and dated reports of each scientist or other professional, e.g., pathologists and 
statisticians, involved in the study should be included.  Reports may be included in the 
appendices. 
 
14.  Accuracy and Completeness Statement 
 
A statement, signed and dated by the investigator, attesting to the accuracy and 
completeness of the FSR and stating whether the data were collected in compliance with 
the study protocol, applicable guidance documents, and regulatory requirements should 
be included. 
 
15.  Location of specimens, raw data, and the final study report 
 
The location where all study documentation is to be stored should be included. 
 
16.  Appendices 
 
All study documentation should appear in the appendices of the FSR.  For a definition of 
study documentation, see the glossary of this guidance. 
 
 
IV.  Target Animal Safety 
 
A.  Content and format of the technical section 
 
1.  Cover letter 
 
The content of the cover letter is administratively used to route the submission to the 
proper review personnel.  Therefore, it is essential to make the purpose of the submission 
explicit in this letter.  The following elements should be included in the cover letter: 
 
  INAD file number 
  Name, address, and telephone number of the sponsor 
  Drug name (include trade name and generic name) 
  Specific purpose of the submission 
  Content/Format of Technical Sections & Final Study Reports  Page 18 of 29 
  Proposed indications 
 
The cover letter and supporting information should be mailed to: Center for Veterinary 
Medicine, Document Control Unit, HFV-199, 7500 Standish Place, Rockville MD 20855 
 
2.  Table of contents 
 
A general table of contents for the technical section is recommended.  Within a particular 
final study report or volume, a more detailed table of contents is also recommended. 
 
3.  Summary of target animal safety studies 
 
The overall summary of target animal safety should cover the developmental history of 
the technical section and summaries of safety study results.  The developmental history is 
a timeline that describes agreements and discussions between the sponsor and CVM, and 
regulatory decisions made by CVM.  The safety summary should include the following 
information (at a minimum):  
 
  Number and identification of target animal safety studies 
  Type of studies (toxicity, tolerance, reproductive safety, etc.) 
  Study Initiation Date, Experimental Phase Initiation/Completion Dates, Study 
Completion Dates 
  Number of investigational animals (treated and control) per study 
  Formulation of drug used in each study (e.g., final market formulation, batch number, 
and other pertinent descriptors) 
  Brief description of results for each study 
 
  Content/Format of Technical Sections & Final Study Reports  Page 19 of 29 
A tabular format is suggested as an efficient way to summarize major aspects of studies.  
For example: 
 
Study  Study  Study  Exper. Phase  Number  Drug 
no.  type:  Initiation &  Initiation &  of  Formulation 
Safety  Completion  Completion  animals 
Dates  Dates 
C032- Toxicity  3/10/95 -  4/11/95-5/11/95  40 adult  final market 
542-97  (0,1,3,5X)  6/10/95  ponies; 10  formulation 
per 
treatment 
group 
C021- Tolerance  1/12/95- 2/13/95-3/13/95  10 adult  final market 
552-97  4/15/95  ponies  formulation 
 
More detailed tables may be used to elaborate upon specific target animal safety 
study results.  Although tables are preferable, text summaries are also acceptable.  
 
4.  Final study reports of target animal safety studies 
 
Non-clinical laboratory safety studies must be conducted in compliance with 21 CFR Part 
58.  If any of the safety studies are not conducted in compliance with 21 CFR Part 58, a 
brief statement as to the reason for noncompliance and why the deviations do not 
invalidate the study shall be included as required by 514.111(a)(11). 
 
Each safety study submitted in support of approval must be summarized in a final study 
report consistent with 58.185.  This guidance also provides a suggested format.  Target 
animal safety studies typically include toxicity, tolerance, and reproductive safety 
studies.  
See CVMs Target Animal Safety Guideline for New Animal Drugs (June 1989) for 
additional information on these safety studies. 
 
5.  All other information pertinent to target animal safety 
 
This section should contain any other information that may be pertinent to evaluating 
product safety.  Consistent with 514.1(b)(8)(iv), CVM may refuse an application if it 
does not contain all information pertinent to the evaluation of the target animal safety and 
effectiveness of the new animal drug and related new animal drugs.  Information such as 
reports in the scientific literature, other studies conducted with the product outside the 
U.S. or any evaluations made by the sponsors veterinary consultants or staff should be 
submitted.  Summaries of this information are acceptable. 
 
 
  Content/Format of Technical Sections & Final Study Reports  Page 20 of 29 
6.  Foreign market experience 
 
This section includes, among other items, the approximate number of units of the product 
sold outside of the United States as well as any adverse reaction reports.  Inclusion of the 
foreign approved product package insert (with English translation) is recommended.  
 
7.  Product labeling 
 
Draft product labeling should be submitted at the time the technical section is submitted.  
Emphasis should be placed on sections of product labeling that relate to target animal 
safety, e.g., contraindications, precautions, and toxicity.  Submission of product labeling 
on an appropriate electronic medium is recommended. 
 
8.  FOI summary 
The section of the FOI (Freedom of Information) summary that relates to target animal 
safety should be submitted at the time the technical section is submitted.  Submission of 
the FOI summary information on an appropriate electronic medium is recommended. 
 
B.  Content and format of a final study report for a safety study 
 
A nonclinical laboratory study, e.g., a target animal safety study, must be conducted in 
compliance with the Good Laboratory Practices regulations (21 CFR Part 58).  One aspect of 
that compliance is the preparation of a final study report (FSR).  An FSR must be prepared 
for each nonclinical laboratory study and must include the information required in 58.185.  
The FSR should be a comprehensive, stand-alone document that provides a clear explanation 
of the study objective(s), experimental materials and methods and a presentation and critical 
scientific evaluation of the results.  The FSR should be written when collection of all raw 
data is complete. The target animal safety technical section should contain FSRs for each 
study conducted in support of target animal safety.   
 
The FSR shall be signed and dated by the study director (58.185(b)).  Any corrections or 
additions to the FSR shall be in the form of an amendment by the study director.  The 
amendment shall clearly identify that part of the FSR that is being added or corrected and the 
reason of the correction or addition, and shall be signed and dated by the person responsible 
(58.185(c)). 
 
The FSR should contain the following elements: 
 
1.  Title page 
 
The title page should contain the following information: 
  Content/Format of Technical Sections & Final Study Reports  Page 21 of 29 
 
  Title of protocol/study 
  Protocol version and study number (this should also appear on each page of the 
report) 
  Investigational new animal drug generic and trade name 
  Proposed indication(s) 
  Sponsor name and  address 
  Testing facility name and address 
  Study director name and address 
  Quality assurance name and address 
  Study initiation and completion dates 
  Experimental initiation and completion dates  
  Study director signature and date 
  Report author(s) signature and date 
 
 
2.  Table of contents 
 
The table of contents should be comprehensive, identifying each section and subsection 
(and associated page number) of the report.  The insertion of tabs is recommended for the 
principal sections. 
 
3.  Summary 
 
A brief summary of the materials and methods, and results of the study should be 
provided. It should describe the critical features of the study, e.g., target population, 
primary parameters, and adverse reactions, and any guidance or regulations that were 
followed during the conduct.  The summary may include text, tables, and graphs. 
 
4.  Objective(s) 
 
A statement under this heading shall describe the overall objective(s) of the study as 
stated in the study protocol (58.185(a)(2)). 
 
5.  Study schedule 
 
A chronological representation of key events of the study and the dates on which they 
occurred, including the study initiation and completion dates and the experimental 
initiation and completion dates. 
 
6.  Study design 
  Content/Format of Technical Sections & Final Study Reports  Page 22 of 29 
 
6.1  Description of treatment groups/experimental design 
 
A rationale and description of the chosen experimental design, e.g., cross-over or 
Latin square, should be provided.  The number of animals per treatment group and a 
description of each treatment group are needed.  The nature of the control group 
should also be discussed  The experimental unit should be defined.  An explanation of 
how the animals were housed should be provided. 
 
6.2  Method of assignment to treatment group 
 
A complete description of the procedure and type (randomization or stratification) of 
the assignment method should be provided.  A discussion of the total number of 
animals and the variables used for randomization, e.g., weight, gender, and age, 
should be included.   
 
6.3  Blinding 
 
If blinding is appropriate to study design, detail the extent of blinding, how the 
blinding was accomplished, and the circumstances under which the treatment code 
may be revealed.   
 
7.  Study procedures 
 
The final study report must include the procedures stated in the protocol (58.185(a)(2)) 
and describe all methods used (58.185(a)(6)).  This section should include all details 
necessary to reconstruct and understand the experimental materials and methods used to 
conduct the study.  Deviations from the protocol should be discussed. 
 
7.1  Test and control articles 
 
7.1.1  Description 
 
A description of the test (investigational new animal drug) and control article(s) 
must be identified in the report by name, chemical abstracts number or code 
number, strength, purity, and composition or other appropriate characteristics 
(58.185(a)(4)).  Other identifying characteristics may include lot or batch 
number, trade name, formulation, dosage form, or manufacturing site. 
 
7.1.2  Storage conditions 
 
  Content/Format of Technical Sections & Final Study Reports  Page 23 of 29 
The storage conditions of the test and control articles during the conduct of the 
study should be described. 
 
7.1.3  Stability 
 
The stability of the test and control articles under the conditions of administration 
must be described (58.185(a)(5)). 
 
7.1.4  Material Safety Data Sheet (MSDS) 
 
The MSDS may be attached as an appendix to this report. 
 
7.2  Investigational animals 
 
7.2.1  Description 
 
A complete description of the investigational (control and treated) animals shall 
be included (58.185(a)(7)).  This description must include, where appropriate, 
the number of treated and control animals, species/breed, age, gender, body 
weight range, source of supply, and procedures used for identification, e.g., 
neckband and tattoo.  The physiological status, e.g., lactating, pregnant, or 
prepubertal, of the animals should also be described. 
 
7.2.2  Owner Consent Forms 
 
The owner consent forms (if appropriate) should be attached as an appendix to 
this report. 
 
7.2.3  Inclusion/exclusion criteria 
 
The selection criteria used to admit animals to the study should be described, 
including any diagnostic requirements, e.g., physical examination, body 
temperature, or reproductive status.  The rationale for and description of the 
inclusion and exclusion criteria should be included.  If any animal is used in the 
study that failed to meet the inclusion criteria, the reason should be provided.  
 
7.2.4  Acclimation of investigational animals 
 
An acclimation period allows animals to adapt to the study environment, e.g., 
housing, handling, and feeding practices.  The final study report should describe 
the location of the animals during the acclimation period, the length of the 
  Content/Format of Technical Sections & Final Study Reports  Page 24 of 29 
acclimation period, any medication(s) and/or vaccines administered during this 
period, and any baseline data collected prior to dose administration. 
 
7.3  Analytical methods 
 
For each analytical method used in the conduct of this study, include, at a minimum, 
a description of the method, a brief methodology (including sample collection, 
preparation and storage; validation; quality control procedures; and supportive 
relevant scientific references), and objective criteria and procedures to assess the 
analytical results.  A certification that all method validations were performed before 
the initiation of the study should be included.  If validations were not performed 
before the start of the study a statement describing the mitigating reasons should be 
included. 
 
7.4  Study facilities 
 
7.4.1  Identification and description 
 
The name and address of the study facilities must be provided (58.185(a)(1)). A 
complete description of these facilities should be provided.  Such a description 
could include a general description of the housing unit(s) including dimensions of 
the pertinent areas used during any phase of the study.  Diagrams may prove 
useful to convey this information. 
 
7.4.2  Management procedures 
 
General management procedures, e.g., equipment maintenance and environmental 
control (temperature, humidity, airflow), may have bearing on the study outcome 
and welfare of the animals and should be described.  Where appropriate, the type, 
frequency and duration of exercise provided to the animals should be described. 
 
7.5.  Feed and Water 
 
7.5.1  Diets 
 
The diets fed to the investigational animals should meet the nutritional 
requirements of the animals.  When necessary, a qualitative and quantitative 
description of the dietary ingredients should be provided.  The frequency of 
feedings and the quantities of feed offered and refused should be described.  
When the test article is administered in feed, drug feed assays should be 
  Content/Format of Technical Sections & Final Study Reports  Page 25 of 29 
discussed, especially in terms of proper drug administration.  Discuss differences, 
if any, in the dietary feed intake between the treated and control animals. 
 
7.5.2  Water 
 
The quality and availability of water offered to the animals and water delivery 
systems should be described. 
 
7.6  Treatment administration  
 
A description of the dosage, dosage regimen, route of administration, and duration 
shall be included (58.185(a)(8)).  Any problems encountered with dosing should be 
discussed as well as observations regarding palatability (if applicable). 
 
7.7  Concomitant medications/therapies 
 
The type, quantity and duration of concomitant medications/therapies should be 
discussed in this section.  The rationale for use and impact of the 
medications/therapies on the study outcome (e.g., drug interaction or effect on a study 
parameter) should be discussed. 
 
7.8  Criteria for animal removal from a study 
 
It is sometimes necessary to remove an animal from study due to sickness, injury or 
other reasons.  The specific criteria for removal should be detailed as well as the 
procedure for removal and, if appropriate, replacement. 
 
7.9  Necropsy procedures  
 
Details of gross necropsy and histopathology should be included.  The number of 
animals, measurements obtained, e.g., clinical pathology parameters, and tissues 
examined and saved should be listed. 
 
7.10  Animal and drug accountability and disposition 
 
The final disposition of all investigational animals (number and procedure for 
disposal) and the investigational new animal drug and control article should also be 
described. 
 
8.  Study variables/observations 
 
  Content/Format of Technical Sections & Final Study Reports  Page 26 of 29 
8.1  Variables measured for evaluating study objectives 
 
Observations include any inspection or examination of investigational animals.  The 
rationale for the variables selected to test the objective of the study should be 
discussed in detail.  In addition, the methods used in assessing the variable should be 
explained or referenced.  The frequency of assessment and the criteria used to 
characterize the measurement of the variable should be stated.  If measurement of a 
variable is derived, the calculations used in the derivation should be provided. 
 
For example, in a safety study for an injectable product to be administered 
intramuscularly, injection site observations should record the presence and degree of 
heat, swelling, redness and pain.  These variables can be scored and used objectively 
to describe adverse effects associated with administration of the drug and/or the 
placebo.   
 
8.2  Other observations recorded during the study 
 
All other types of observations should be discussed such as animal care observations, 
food consumption observations, etc. 
 
9.  Data calculations and statistical methodologies and analyses 
 
A description of all transformations, calculations, or operations performed on the data 
(58.185(a)(11)) and the statistical methods employed for analyzing the data 
(58.185(a)(3)) must be included.  The statistical portion of the report is not a printout of 
the data analysis (which should be included as an appendix) but rather, is a description of 
the data and procedures.  The differences that exist, if any, between the data set subjected 
to statistical analyses and the complete raw data should be identified.   The experimental 
unit and the number of replicates per treatment should be defined.  The statistical 
methodology should be described including the hypotheses tested, any estimated 
parameters or assumptions and any specific statistical model used.  If any data 
transformations were performed, a rationale for the choice of transformation as well as 
the impact on treatment effects should be discussed.  A description of how the results 
were used to draw conclusions about the study's objective(s) and the appropriateness of 
the choice of statistical method should be provided.  Where the actual transformations, 
calculations, or operations performed on the data or the actual statistical methods 
employed to analyze the data differ from that stated in the protocol, a rationale for such 
deviation should be included. 
 
10.  Results 
 
  Content/Format of Technical Sections & Final Study Reports  Page 27 of 29 
All data collected during the study must be summarized and analyzed (58.185(a)(11)).  
The results for each protocol-defined variable used as evidence to support safety should 
be presented as text, tables or graphs (as appropriate).  The exact location (appendix page 
numbers) of the supporting raw data should be referenced.  Tables and graphs should be 
concise and user-friendly, since individual data will be located in the appendices. 
 
11.  Conclusions/discussion 
 
An overall statement of the conclusions drawn from the analysis of the data regarding the 
target animal safety of the product must be included (58.185(a)(11)).  Furthermore, a 
description of all circumstances that may have affected the quality or integrity of the data 
must be included (58.185(a)(9)).  New or unexpected findings and their impact on the 
study outcome should be identified.  Adverse events and their potential impact and any 
results, which may be inconsistent with the overall study conclusions, should also be 
discussed in detail. 
 
12.  Personnel 
 
The name of the study director, the names of other scientists or professionals, and the 
names of supervisory personnel involved in the study must be included (58.185(a)(10)). 
 
13.  Reports 
 
The signed and dated reports of each scientist or other professional, e.g., pathologists and 
statisticians, involved in the study must be included (58.185(a)(12)).  Reports may be 
included in the Appendix. 
 
14.  QA Statement 
 
A statement prepared and signed by the quality assurance unit as described in 
58.35(b)(7) must be included (58.185(a)(14)). 
 
15.  Location of specimens, raw data, and the final study report 
 
The location where all specimens, raw data, and the final study report are to be stored 
must be included (58.185(a)(13)). 
 
  Content/Format of Technical Sections & Final Study Reports  Page 28 of 29 
 
16.  Appendices 
 
All study documentation should be included in the Appendices of the FSR.  For a 
definition of study documentation, see the glossary of the guidance.  Raw data should be 
submitted for all studies unless otherwise agreed upon with CVM.