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July 6, 2010 

VETERINARY SERVICES MEMORANDUM NO. 800.207 

TO: VS Management Team (VSMT) 

 Directors, Center for Veterinary Biologics 

 Biologics Licensees, Permittees, and Applicants 

FROM: John R. Clifford /s/ Jere L. Dick, for 

Deputy Administrator 

 Veterinary Services 

SUBJECT: General Licensing Considerations: Target Animal Safety (TAS) Studies 

Prior to Product Licensure - VICH Guideline 44 

I. PURPOSE 

This document provides guidance to veterinary biologics licensees and permittees 

concerning the design and execution of safety studies to support an application for a 

U.S. Veterinary Biological Product License or U.S. Veterinary Biological Product Permit 

for Distribution and Sale according to Title 9, Code of Federal Regulations (9 CFR), 

Parts 102.5 and 104.5. The scope of this guideline is limited to prelicensing studies and 

applicable safety studies conducted to support new and/or revised label claims. 

Although this guideline represents current policy regarding TAS, it does not confer rights 

for, or on, any person and does not operate to bind APHIS or the public. An alternative 

approach may be used if such approach satisfies the requirements of the applicable 

statute, regulation, or both. 

II. BACKGROUND 

Target Animal Safety Studies are required for the issuance of a U.S. Veterinary 

Biological Product License or a U.S. Veterinary Biological Product Permit for 

Distribution and Sale. This document provides guidance to veterinary biologics licensees 

and permittees regarding the design and execution of such studies. In addition, we have 

appended another guideline (Topic GL- 44) that contains the recommendations of the 

International Cooperation on Harmonization of Technical Requirements for the 

Registration of Veterinary Medicinal Products (VICH) concerning target animal safety 

studies. 

VICH Topic GL- 44, Target Animal Safety Studies for Veterinary Live and Inactivated 

Vaccines, has been adopted as an international standard for conducting target animal 

safety studies for veterinary live and inactivated vaccines and represents current APHIS 

policy regarding the generation and submission of target animal safety data for veterinary 

United States 

Department of 

Agriculture

Animal and Plant 

Health Inspection 

Service 

Veterinary Services 

Washington, DC 

20250 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

 Page 2 

biologics. The recommendations contained herein are provided as an aid in preparing 

protocols for safety studies conducted under laboratory conditions and any related field 

safety studies. On a product-by-product basis, some recommended studies may be 

unnecessary and/or additional studies not described in this document may be needed to 

address specific safety concerns. Contact the Center for Veterinary Biologics–Policy, 

Evaluation, and Licensing if you have questions concerning the appropriateness of certain 

studies. 

Further detailed guidance specific to target animal backpassage and field safety studies 

can be found in Veterinary Services Memorandums (VSM) 800.201 and 800.204, 

respectively. 

III. GUIDELINES 

A. General 

1. The specific information required to demonstrate TAS of a biologic proposed 

for licensure depends on many factors, including the proposed usage regimen 

and dose, type of biologic, nature of adjuvants, excipients, claims, previous 

use history of similar products, species, class, and breed. 

2. Generally, the data from safety tests on combined vaccines may be used to 

demonstrate the safety of vaccines containing fewer antigen and/or adjuvant 

components provided the remaining components are identical in each case and 

it is only the number of antigens and/or adjuvant components that has 

decreased. 

3. Adverse events must be described and included in the final report and 

determination of causality for the adverse event attempted. 

4. TAS studies done under laboratory conditions should be performed and 

managed in accordance with the principles of Good Laboratory Practices. 

5. The animals should be appropriate for the purpose of the test with regard to 

species, age, weight/size, and class for which the proposed biological product 

will be used. Treated and control animals (when used) should be managed 

similarly. Housing and husbandry should be adequate for the purpose of the 

study and should conform to local animal welfare regulations. Reduction or 

elimination of suffering during the study is essential. Euthanasia and necropsy 

of moribund animals are recommended. 

6. In laboratory studies, the safety implications are best addressed by applying 

descriptive statistical methods to the data. 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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B. Laboratory Safety Tests 

1. VICH GL44 provides guidance regarding licensure of live vaccines shown to 

retain residual pathogenicity by induction of disease specific signs or lesions. 

The guidance included in VICH GL44 regarding overdose testing of these live 

vaccines pertains to prelicensing studies. Note that host animal overdose 

safety tests defined in 9 CFR 113.39, 113.40, 113.41, 113.44, and 113.45 

describe testing performed on final products for serial release. In most 

circumstances, these tests, when conducted with prelicense serials, will satisfy 

overdose safety tests for cats, dogs, cattle, swine, and sheep for products 

intended for distribution in the U.S. 

2. VICH GL44 also describes one dose and repeat dose tests in the target animal 

species. In most circumstances, the successful completion of the field safety 

study will satisfy this requirement for products intended for distribution in the 

U.S. 

C. Reproductive Safety Tests 

1. VICH GL44 provides guidance regarding prelicense safety tests of products 

for use in breeding animals. If the reproductive safety studies are not 

performed, an exclusion statement must be included on the label, unless a 

scientific justification for absence of risk in the breeding animal is provided. 

2. Further guidance related to modified live bovine vaccines that contain 

infectious bovine rhinotracheitis and/or bovine viral diarrhea virus may be 

reviewed in VSM 800.110. 

D. Field Safety Tests 

1. VICH GL44 provides guidance regarding prelicensing field safety studies. 

When disease and husbandry are similar between regions participating in the 

VICH, international data may be used to support field safety, as long as a 

minimum proportion of the data, acceptable to the regional authorities, is 

generated within the region where approval is being sought. For products 

intended for distribution in the U.S., data generated in VICH-participating 

regions will be considered for substitution of one U.S. geographical site, 

provided that husbandry conditions are determined to be comparable to those 

in the U.S. 

2. Further guidance related to field safety studies may be reviewed in 

VSM 800.204. 

Attachment 

Attachment 1 – Appendix I 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

Page 1 

Appendix I 

 

Target Animal Safety for Veterinary 

Live and Inactivated Vaccines 

Adopted at Step 7 of the VICH Process 

by the VICH Steering Committee 

in July 2008 

for implementation in July 2009

THIS GUIDELINE HAS BEEN DEVELOPED BY THE APPROPRIATE VICH EXPERT WORKING GROUP AND 

HAS BEEN SUBJECT TO CONSULTATION BY THE PARTIES, IN ACCORDANCE WITH THE VICH PROCESS. 

AT STEP 7 OF THE PROCESS THE FINAL DRAFT IS RECOMMENDED FOR ADOPTION TO THE REGULATORY 

BODIES OF THE EUROPEAN UNION, JAPAN AND USA. 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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Table of Contents 

1. INTRODUCTION 

1.1. Objective 

1.2. Background 

1.3. Scope 

1.4. General Principles 

1.4.1. Standards 

1.4.2. Animals 

1.4.3. IVV and Route of Administration 

1.4.4. Study Design 

1.4.5. Statistical Analysis 

2. GUIDELINES 

2.1. Laboratory Safety Tests 

2.1.1. Overdose Test for Live Vaccines 

2.1.2. One Dose and Repeat Dose Test 

2.1.3. Data Collection 

2.2. Reproductive Safety Test 

2.3. Field Safety Test 

2.3.1. Animals 

2.3.2. Study Sites and Treatment 

2.3.3. Data Collection 

3. GLOSSARY 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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1. INTRODUCTION 

Submission of target animal safety (TAS) data is a requirement for the registration or 

licensure of veterinary live and inactivated vaccines in the regions participating in the 

VICH. International harmonization will minimize the need to perform separate studies for 

regulatory authorities of different countries. Appropriate international standards will 

reduce research and development costs by avoiding, when possible, duplication of TAS 

studies. Animal welfare will benefit because fewer animals will be needed by eliminating 

repetition of similar studies in each region. 

This guideline has been developed under the principle of VICH and will provide a unified 

standard for government regulatory bodies to facilitate the mutual acceptance of TAS 

data by the relevant authorities. The use of this VICH guideline to support registration of 

a product for local distribution only is strongly encouraged but is up to the discretion of 

the local regulatory authority. Furthermore, it is not always necessary to follow this 

guideline when there are scientifically justifiable reasons for using alternative 

approaches. 

1.1. Objective 

This guideline establishes agreed criteria and recommendations for the conduct of studies 

that evaluate the safety of final formulation of veterinary live and inactivated vaccines 

(investigational veterinary vaccines, IVVs) to be marketed for use in target animals. 

1.2. Background 

The VICH TAS Working Group was formed to develop an internationally harmonized 

guideline outlining recommendations for meeting regulatory requirements for the 

registration of IVVs in the regions participating in the initiative. By their nature, 

guidelines address most, but not all possibilities. General principles are included in this 

guideline to aid in the development of TAS study protocols. 

It is important to emphasize that the international acceptance of data remains a 

fundamental principle for VICH. 

1.3. Scope 

This guideline is intended to cover safety studies of IVVs including genetically 

engineered products used in the following species: bovine, ovine, caprine, feline, canine, 

porcine, equine and poultry (chickens and turkeys). This document does not cover TAS 

studies conducted as part of post-approval batch release requirements. Products for use in 

minor species or minor uses may be exempted from this requirement for local 

registration. The guideline will not provide information for the design of TAS studies in 

other species including aquatic animals. For other species, TAS studies should be 

designed following national or regional guidance. Additional requirements may apply to 

genetically engineered products according to the region in which authorization is sought. 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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Immune modulators are not considered in this guideline. During development, animal 

safety shall be evaluated in the target animal. The purpose of the evaluation is to 

determine the safety of the dose of the vaccine proposed for registration. The guideline is 

therefore limited to the health and welfare of the target animals. It does not include 

evaluation of food safety or environmental safety including impact on human health. 

The guideline is a contribution towards international harmonization and standardization 

of methods used for evaluation of target animal safety of IVVs. The guideline is provided 

to aid sponsors in preparing protocols for TAS studies conducted under laboratory 

conditions and in related field studies (which use a larger number of animals). All studies 

may not be needed. Additional studies not specified in this document and necessary to 

investigate specific safety concerns of the vaccine in the target animal may be necessary 

for certain IVVs. Therefore, specific additional information not specified in this 

document may be determined by communication between the sponsor and the regulatory 

authority. 

Reversion to virulence is dealt with in a separate VICH guideline (GL 41). 

1.4. General Principles 

The specific information required to demonstrate target animal safety of an IVV depends 

upon factors such as proposed usage regimen and dose, type of IVV, nature of adjuvants, 

excipients, claims, previous use history of similar product, species, class, and breed. 

Generally, the data from safety tests on combined vaccines may be used to demonstrate 

the safety of vaccines containing fewer antigen and/or adjuvant components provided the 

remaining components are identical in each case and it is only the number of antigens 

and/or adjuvant which has decreased. In some regions, this approach may not apply to 

field safety studies. In this case, each combination of antigens/adjuvant in the final 

formulation intended to be registered has to be tested. 

Adverse events must be described and included in the final report and determination of 

causality for the adverse event attempted. 

1.4.1. Standards 

TAS studies done under laboratory conditions should be performed and managed in 

accordance with the principles of Good Laboratory Practices (GLP), for example the 

Organization for Economic Co-operation and Development (OECD), and field safety 

studies should be conducted in conformity with the principles of VICH Good Clinical 

Practices (GCP). 

1.4.2. Animals 

The animals should be appropriate for the purpose of the test with regard to species, age 

and class for which the IVV will be used. Treated and control animals (when used) are 

managed similarly. The environmental conditions of the groups should be as similar as 

possible. Housing and husbandry should be adequate for the purpose of the study and 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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conform to local animal welfare regulations. Animals should be appropriately 

acclimatized to the study conditions. Appropriate prophylactic treatment should be 

completed before initiation of the study. Reduction or elimination of suffering during the 

study is essential. Euthanasia and necropsy of moribund animals is recommended. 

1.4.3. IVV and Route of Administration 

The IVV and the routes and methods of administration should be appropriate for each 

type of study as described later in this document. 

1.4.4. Study Design 

Where studies performed by a sponsor differ from those specified in this document, the 

sponsor may conduct a literature search and combine these findings with the results of 

any preliminary experiments to justify any alternative TAS study designs. Essential 

parameters to be evaluated for the safety of a vaccine are local and systemic reactions to 

vaccination, including application site reactions and their resolution and clinical 

observation of the animals. The reproductive effects of the vaccine shall be evaluated 

where applicable. 

Special tests may be required, such as hematology, blood chemistry, necropsy or 

histological examination. Where these tests are conducted in a subset of animals, these 

animals should be randomly selected with adequate sampling rate before study initiation 

to avoid bias, unless otherwise justified. In case of unexpected reactions or results, 

samples should be selected appropriately in order to identify the cause of the problem 

observed, if possible. 

 

Whenever possible, the personnel collecting data in the studies should be masked 

(blinded) to treatment identification to minimize bias. Pathologists are not required to be 

masked to the type of IVV and the possible clinical effects but should be masked to the 

treatment groups. Histopathology data should be evaluated by recognized procedures 

(e.g., Crissman et al., Toxicologic Pathology, 32 (1), 126-131, 2004).

1.4.5. Statistical Analysis 

In laboratory studies the safety implications are best addressed by applying descriptive 

statistical methods to the data. Tables and descriptive text are common methods of data 

summarization; however, it may also be valuable to make use of graphical presentations 

in which patterns of adverse events are displayed both within treatments and within 

individual animals. In field studies, if applicable, selection of the general form for a 

statistical model and the factors to be included in the model will depend on the nature of 

the response variable being analyzed and the study design. Regardless of the methods 

chosen, the process and steps used to conduct any statistical evaluations should be 

described. The outcomes of the data analysis should be clearly presented to facilitate 

evaluation of potential safety concerns. The terminology and methods of presentation 

should be chosen to clarify the results and expedite interpretation. 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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Although there may be interest in the null hypothesis of no difference between 

treatments, study design constraints limit the statistical power and discriminatory ability 

of these studies. Under these conditions, statistical analysis alone may not detect 

potential adverse effects and thus provide assurance of safety. A statistically significant 

test does not necessarily indicate the presence of a safety concern. Similarly, a nonsignificant test does not necessarily indicate the absence of a safety concern. Results 

should therefore be evaluated based on statistical principles but interpretation should be 

subject to veterinary medical considerations. 

2. GUIDELINES 

Target animal safety for IVV is determined using laboratory and field studies. For both 

live and inactivated vaccines, any data collected which could be related to the safety of 

IVV should be reported from studies conducted during development phase of the IVV. 

These data may be utilized to support TAS laboratory study design and to identify critical 

parameters to be examined. 

Laboratory safety studies are designed to be the first step in evaluating target animal 

safety and provide basic information before initiating the field studies. The design of 

laboratory safety studies will vary with the type of product and intended use of the 

product being tested. 

2.1. Laboratory Safety Tests 

2.1.1. Overdose Test for Live Vaccines 

For live vaccines shown to retain residual pathogenicity by induction of disease specific 

signs or lesions, overdose testing of the live vaccine component should be conducted as 

part of the risk analyses for the acceptability of the micro-organism as vaccine strain. The 

study should be conducted using either a pilot or production batch. A 10X dose based on 

the maximum release titer for which the application is submitted shall be administered. In 

the case where the maximum release titer to be licensed is not specified, the study should 

be conducted with a justifiable multiple of the minimum release titer, taking into account 

the need to ensure an appropriate safety margin. Exceptions need to be scientifically 

justified. Generally eight animals per group should be used unless otherwise justified. If 

adjuvant or other components are contained in a diluent for the live vaccine, the amount 

and concentration in a dose administered should be as proposed and justified in the draft 

registration dossier. If a 10X titer of antigen cannot be dissolved in 1X dose volume, then 

a double dose or other minimum volume of diluent sufficient to achieve dissolution 

should be used. The inoculum may be administered using multiple injection sites if 

justified by the required dose volume or the target species. 

In general other vaccines do not require overdose testing. 

Generally, for each target species, the most sensitive class, age and sex proposed on the 

label should be used. Seronegative animals should be used. In cases where seronegative 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

Page 7 

animals are not reasonably available, alternatives should be justified. If multiple routes 

and methods of administration are specified for the product concerned, administration by 

all routes is recommended. If one route of administration has been shown to cause the 

most severe effects, this single route may be selected as the only one for use in the study. 

Where applicable, the titer or potency of the batches used for safety testing, particularly 

the overdose studies, will form the basis for establishing the maximum release titer or 

potency for batch release. 

2.1.2. One Dose and Repeat Dose Test 

For vaccines that require a single life time dose or primary vaccination series only, the 

primary vaccination regimen should be used. For vaccines that require a single dose or 

primary vaccination series followed by booster vaccination, the primary vaccination 

regimen plus an additional dose should be used. For convenience, the recommended 

intervals between administrations may be shortened to an interval of at least 14 days. 

Evaluation of the one/repeat dose testing should be conducted using either a pilot or 

production batch of IVV containing the maximum release potency or, in the case where 

maximum release potency to be licensed is not specified, then a justified multiple of the 

minimum release potency should be used. 

Generally, eight animals per group should be used unless otherwise justified. Generally, 

for each target species, the most sensitive class, age and sex proposed on the label should 

be used. Seronegative animals should be used for live vaccines. In cases where 

seronegative animals are not reasonably available, alternatives should be justified. 

If multiple routes and methods of administration are specified for the product concerned, 

administration by all routes is recommended. If one route of administration has been 

shown to cause the most severe effects, this single route may be selected as the only one 

for use in the study. 

2.1.3. Data Collection 

General clinical observations appropriate for the type of IVV and animal species should 

be made every day for 14 days after each administration. In addition, other relevant 

criteria such as rectal temperature (for mammals) or performance measurement are 

recorded within this observation period with appropriate frequency. All observations 

should be recorded for the entire period. Injection sites should be examined daily or at 

other justified intervals by inspection and palpation for a minimum of 14 days after each 

administration of the IVV. When injection site adverse reactions are present at the end of 

the 14 days observation, the observation period should be extended until clinically 

acceptable resolution of the lesion has occurred or, if appropriate, until the animal is 

euthanized and histopathological examination is performed. 

2.2. Reproductive Safety Test 

Examinations of reproductive performance of breeding animals must be considered when 

data suggest that the starting material from which the product is derived may be a risk 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

Page 8 

factor. The laboratory studies in concert with the field safety studies (detailed in 2.3.) are 

required to support use in breeding animals. If the reproductive safety studies are not 

performed, an exclusion statement must be included on the label, unless a scientific 

justification for absence of risk for use of the IVV in the breeding animal is provided. 

The design and extent of the laboratory and field safety studies will be based upon the 

type of organism(s) involved, the type of vaccine, timing and route of delivery, and the 

animal species involved. 

For examination of reproductive safety, animals appropriate for the purpose of the study 

will be vaccinated with at least the recommended dose according to the vaccination 

scheme indicated. If multiple routes and methods of administration are specified for the 

product concerned, administration by all routes is recommended. If one route of 

administration has been shown to cause the most severe effects, this single route may be 

selected as the only one for use in the study. Generally, eight animals per group should be 

used unless otherwise justified using either a pilot or production batch. The animals 

should be observed for a period appropriate to determine reproductive safety, including 

daily safety observations specified in 2.1.3. Exceptions should be justified. A control 

group should be included. 

Vaccines recommended for use in pregnant animals must be tested as described above in 

each of the specific periods of gestation recommended for use on the label. An exclusion 

statement will be required for those gestation periods not tested. The observation period 

must be extended to parturition, to examine any harmful effects during gestation or on 

progeny. Exceptions should be justified. 

When scientifically warranted, additional studies may be required to determine the 

effect(s) of IVV on semen, including shedding of the live organism in semen. The 

observation period should be appropriate for the purpose of the study. 

For IVVs recommended for use in future layers or laying hens, study design should 

include evaluation of parameters that are appropriate for the class of hens vaccinated. 

2.3. Field Safety Test 

Where disease and husbandry are similar between regions participating in the VICH, 

international data may be used for field studies, as long as a minimum proportion of the 

data, acceptable to the regional authorities, is generated within the region where approval 

is being sought. It is the responsibility of the sponsor to ensure that field studies should 

be conducted under animal husbandry conditions representative of those regions in which 

authorization is sought. Local authorizations must be obtained prior to conduct of the 

study. Consultation with regional regulatory authorities regarding study design prior to 

conduct of the studies is recommended. 

If a label indicates use in breeding animals, appropriate field safety studies need to be 

performed to show the safety of the IVV under field conditions. 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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2.3.1. Animals 

The animals should be in the age range/class intended for treatment as indicated in the 

proposed labeling. Serological status may be considered. Whenever possible either a 

negative or positive control group is included. 

Treated and control animals are managed similarly. Housing and husbandry should be 

adequate for the purpose of the study and conform to local animal welfare regulations. 

2.3.2. Study Sites and Treatment 

Two or more different geographical sites are recommended. The recommended dosage(s) 

and route(s) for vaccination should be used. The studies should be conducted using 

representative batch(es) of the IVV. Some regions may require that the field safety study 

be performed using more than one batch of product.

2.3.3. Data Collection 

Observations should be made over a period of time appropriate for the IVV and adverse 

events should be documented and included in the final report. Reasonable attempts 

should be made to determine causality for the adverse event. 

3. GLOSSARY 

Adverse Effect: Adverse event suspected to be related to an IVV. 

Adverse Event: Any observation that is unfavorable and unintended and occurs after the 

use of an IVV, whether or not considered to be product related. 

Class: Subset of target animal species which is characterized by factors such as 

reproductive status and/or use (dairy vs. beef, broiler vs. layer). 

Dosage: The amount of the IVV dose including volume or potency of the vaccine given 

(mL), frequency and duration of administration. 

Field Safety Study: Clinical study conducted using the IVV under actual marketing 

conditions and following labeling indications to assess efficacy and/or safety. 

Good Clinical Practices (GCP): A standard for the design, conduct, monitoring, 

recording, auditing, analysis, and reporting of clinical studies. Adherence to the standard 

provides assurance that the data and reported results are complete, correct and accurate, 

that welfare of the study animals and the safety of the study personnel involved in the 

study are ensured, and that the environment and the human and animal food chains are 

protected. 

Good Laboratory Practices (GLP): A standard for the design, conduct, monitoring, 

recording, auditing, analysis, and reporting of non-clinical studies. Adherence to the 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

Page 10 

standard provides assurance that the data and reported results are complete, correct and 

accurate, that welfare of the study animals and the safety of the study personnel involved 

in the study are ensured, and that the environment and the human and animal food chains 

are protected. 

Investigational Veterinary Vaccine (IVV): Any live or killed vaccines being evaluated 

in a clinical or non-clinical study, to investigate any protective, therapeutic, diagnostic, or 

physiological effect when administered or applied to an animal. 

Masking/Blinding: A procedure to reduce potential study bias in which designated 

study personnel are kept uninformed of the treatment assignment(s). 

Maximum Release Potency: The expected maximum antigen content allowed at the 

time of release expressed in units appropriate for the IVV. 

Maximum Release Titer: The expected highest number of viable organisms allowed per 

dose in a vaccine at the time of release, verified by safety studies. 

Minimum Release Potency: The expected minimum antigen content allowed at the time 

of release expressed in units appropriate for the IVV. 

Minimum Release Titer: The expected lowest number of viable organisms required per 

dose in a vaccine at the time of release, verified by efficacy and stability studies. 

Negative Control: Healthy animals that are untreated or which receive a vehicle, 

placebo or sham treatment. 

Pilot Batch: A batch of an IVV manufactured by a procedure fully representative of and 

simulating that to be applied at commercial scale. The methods of cell expansion, harvest, 

and product purification should be identical except for the scale of production. 

Positive Control: Healthy animals that are given a similar vaccine, which is normally 

registered in the country in which the study is conducted. This product is chosen by the 

company (the sponsor), and it is indicated for the disease and the target species claimed 

for the tested IVV. 

Production Batch: A batch of an IVV manufactured in the intended production facility 

by the method described in the application. 

Protocol: A document that fully describes the objective(s), design, methodology, 

statistical considerations and organization of a study. The document is signed and dated 

by the investigator for clinical studies (or study director for GLP studies) and the sponsor. 

The protocol may also give the background and rationale for the study but these could be 

provided in other study protocol-referenced documents. The term includes all protocol 

amendments. 
VETERINARY SERVICES MEMORANDUM NO. 800.207 

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Residual Pathogenicity: The potential of viruses or bacteria which have been attenuated 

for specific target animal species and for specific routes of administration to induce 

clinical signs or lesions of disease or persistence/latency of the micro-organism in the 

body of vaccinated animals.