July 26, 2001

VETERINARY SERVICES MEMORANDUM NO. 800.301

Subject: Good Clinical Practice

To: Biologics Licensees, Permittees, and Applicants

Directors, Center for Veterinary Biologics

This guideline provides information and recommendations about the design and conduct of

all clinical studies of veterinary products in the target species. It is the result of a

collaborative initiative by regulatory authorities and industry associations known as

International Cooperation on Harmonization of Technical Requirements for the

Registration of Veterinary Medicinal Products (VICH). One objective of VICH is to

promote harmonization of regulatory requirements for veterinary medicinal products by

reducing the differences in technical requirements for such products among regulatory

agencies in different countries. As a VICH member, APHIS is committed to seeking

scientifically based harmonized technical requirements for veterinary biological products.

VICH has adopted this guideline as an international standard to ensure that clinical studies

are conducted and documented in accordance with the principles of Good Clinical Practice

(GCP).

APHIS will consider the guidance and recommendations in this guideline as a basis for

reviewing clinical study data that are submitted in support of applications for United States

Veterinary Biological Product Licenses or applications for United States Veterinary

Biological Product Permits for General Distribution and Sale. Although this guideline

represents the agency’s current thinking on the design and conduct of clinical studies of

veterinary products in the target species, 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, regulations, or both.

I. INTRODUCTION 

The objective of this document is to provide guidance on the design and conduct of all

clinical studies of veterinary products in the target species.

It is directed at all individuals and organizations involved in the design, conduct,

monitoring, recording, auditing, analysis, and reporting of clinical studies in target species

and is intended to ensure that such studies are conducted and documented in accordance

with the principles of Good Clinical Practice (GCP).

Good Clinical Practice is intended to be an international ethical and scientific quality

standard for designing, conducting, monitoring, recording, auditing, analyzing, and

reporting clinical studies evaluating veterinary products. Compliance with this standard 
Veterinary Services Memorandum No. 800.301 2

provides public assurance about the integrity of the clinical study data and that due regard

has been given to animal welfare and protection of the personnel involved in the study, the

environment, and the human and animal food chains.

This guidance has been developed under the principles of the International Cooperation on

Harmonization of Technical Requirements for Registration of Veterinary Medicinal

Products (VICH) and will provide a unified standard for the European Union (EU), Japan,

and the United States of America (USA) to facilitate the mutual acceptance of clinical data

by the relevant regulatory authorities. This guidance was developed with consideration of

the current practices in the EU, Japan, and the USA together with those of Australia and

New Zealand.

This guidance should be followed when developing clinical study data that are intended to

be submitted to regulatory authorities.

This guidance document represents the current best judgment of the relevant regulatory

authorities on good clinical practices. It does not create or confer rights for or on any

person and does not operate to bind the relevant regulatory authorities or the public. An

alternative approach may be used if such an approach satisfies the applicable regulatory

requirements. If a sponsor chooses to use alternative procedures or practices, discussion

with the regulatory authority is advised.

When a guidance document states a requirement imposed by the law, the requirement is

law and its force and effect are not changed in any way by virture of its inclusion in the

guidance document.

II. GLOSSARY (1)

1.1. Adverse Event (AE) 

Any observation in animals that is unfavorable and unintended and occurs after

the use of a veterinary product or investigational veterinary product, whether

or not considered to be product related. 

1.2. Applicable Regulatory Requirement(s)

Any law(s) and regulation(s) of the relevant regulatory authority addressing

the conduct of studies using investigational veterinary products.
Veterinary Services Memorandum No. 800.301 3

1.3. Audit

A systematic and independent examination of study related activities and

documentation to determine whether the study being evaluated is or was

properly conducted and whether the data are or were recorded, analyzed, and

accurately reported according to the study protocol, study related standard

operating procedures (SOPs), Good Clinical Practice (GCP), and the

applicable regulatory requirements.

1.4. Authenticated Copy

A copy, which is a complete reflection of an original document, that bears or

contains a statement, signed and dated by the idividual(s) making the copy,

certifying that such copy is complete and accurate.

1.5. Blinding (Masking)

A procedure to reduce potential study bias in which designated study

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

1.6. Case Report Forms/Data Capture Forms/Record Sheets

Printed, optical, electronic, or magnetic documents specifically designed to

record study protocol-required and other observations of study animals or

laboratory results.

1.7. Clinical Study

A single scientific experiment conducted in a target species to test at least one

hypothesis relevant to the proposed effectiveness claim(s) or to in-use safety in

the target animal for a veterinary product under investigation. For the purpose

of this guidance, the term clinical study and study are synonymous.

1.8. Compliance (in relation to studies)

Adherence to the study protocol, relevant SOPs, Good Clinical Practice, and

the applicable regulatory requirements.
Veterinary Services Memorandum No. 800.301 4

1.9. Control Product

Any approved product used according to label directions, or any placebo, used

as a reference in a clinical study for comparison with the investigational

veterinary product under evaluation.

1.10. Contract Research Organization (CRO)

An individual or organization contracted by the sponsor or investigator to

perform one or more of the obligations of the sponsor or investigator.

1.11. Disposal of Investigational Veterinary Products

The fate of investigational veterinary and control products during or following

completion of the study. For example, after complying with any restrictions to

minimize public health concerns, the products may be returned to the sponsor,

incinerated, or disposed of by other approved methods.

1.12. Disposal of Study Animals

The fate of the study animals or their edible products during or following

completion of the study. For example, after complying with any restrictions to

minimize public health concerns, animals may be slaughtered, returned to the

herd, sold or returned to their owner.

1.13. Final Study Report (FSR)

A comprehensive description of a study of an investigational veterinary

product that is written after the collection of all raw data is complete or the

study is discontinued and that completely describes the objectives and

experimental materials and methods (including statistical analyses), presents

the study results and contains a critical evaluation of the study results.

1.14. Good Clinical Practice (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 the 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.
Veterinary Services Memorandum No. 800.301 5

1.15. Informed Consent

A documented process by which an owner or owner’s agent voluntarily

confirms the owner’s willingness to allow their animal(s) to participate in a

particular study, after having been informed of all aspects of the study that are

relevant to the decision to participate. 

1.16. Inspection

The act by a relevant regulatory authority of conducting, in accordance with its

legal authority, an official review of study documentation, facilities,

equipment, finished and unfinished materials (and associated documentation),

labeling, and any other resources related to the registration of an

investigational veterinary product and that may be located at any site related to

the study.

1.17. Investigational Veterinary Product

Any biological or pharmaceutical form of, or any animal feed containing one

or more active substances being evaluated in a clinical study, to investigate

any protective, therapeutic, diagnostic, or physiological effect when

administered or applied to an animal.

1.18. Investigator

An individual responsible for all aspects of the conduct of a study at a study

site. If a study is conducted by a group of individuals at a study site, the

investigator is the leader of the group.

1.19. Monitor

An individual responsible for overseeing a clinical study and ensuring that it is

conducted, recorded, and reported in accordance with the study protocol,

Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and

the applicable regulatory requirements.

1.20. Multicenter Study

A study conducted according to a single study protocol at more than one site.
Veterinary Services Memorandum No. 800.301 6

1.21. Quality Assurance (QA)

A planned and systematic process established to ensure that a study is

performed and the data are collected, documented (recorded) and reported in

compliance with this guidance and the applicable regulatory requirements.

1.22. Quality Control (QC)

The operational techniques and activities undertaken within the quality

assurance system to verify that the requirements for quality of the study-related

activities have been fulfilled.

1.23. Randomization

The process of assigning study animals (or groups of study animals) to

treatment or control groups using an element of chance to determine the

assignments in order to reduce bias.

1.24. Raw Data

Any original worksheets, calibration data, records, memoranda and notes of

firsthand 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, magnetic, electronic or optical media,

information recorded from automated instruments, and hand recorded

datasheets. Facsimile transmissions and transcribed data are not considered

raw data.

1.25. Regulatory Authorities

Bodies having the statutory power to regulate. In this guidance, the expression

‘regulatory authorities’ includes the authorities that review submitted clinical

data and conduct inspections.

1.26. Sponsor

An individual, company, institution or organization which takes responsibility

for the initiation, management, and financing of a clinical study for the

veterinary product under investigation.
Veterinary Services Memorandum No. 800.301 7

1.27. Standard Operating Procedure (SOP)

A detailed, written instruction to facilitate consistency in the performance of a

specific function.

1.28. Study Animal

Any animal that participates in a clinical study, either as a recipient of the

investigational veterinary product or as a control.

1.29. Study Protocol

A document signed and dated by the investigator and the sponsor that fully

describes the objective(s), design, methodology, statistical considerations, and

organization of a study. The study protocol may also give the background and

rationale for the study but these could be provided in other study

protocol-referenced documents. Throughout this guidance the term study

protocol includes all study protocol amendments.

1.30. Study Protocol Amendment

A written change or modification of the study protocol effected prior to the

implementation of the protocol or execution of the changed or modified task.

Study protocol amendments should be signed and dated by the investigator and

sponsor and incorporated into the study protocol.

1.31. Study Protocol Deviation

A departure from the procedures stated in the study protocol. Study protocol

deviations should be recorded as a statement signed and dated by the

investigator describing the deviation and the reason for its occurrence (if

identifiable).

1.32. Target Animal

The specific animal by species, class and breed identified as the animal for

which the investigational veterinary product is intended for use.

1.33. Veterinary Product

Any product with approved claims to having a protective, therapeutic or

diagnostic effect or to affect physiological functions when administered to or 
Veterinary Services Memorandum No. 800.301 8

applied to an animal. The term applies to therapeutics, biologicals,

diagnostics, and modifiers of physiological function.

III. THE PRINCIPLES OF VICH GCP (2)

2.1. The purpose of the VICH GCP is to establish guidance for the conduct of

clinical studies that ensures the accuracy, integrity, and correctness of data. Due regard

should be given to the welfare of the study animals, the effects on the environment and the

study personnel and to residues in the edible products derived from food-producing study

animals. 

2.2. Pre-established systematic written procedures for the organization, conduct,

data collection, documentation and verification of clinical studies are necessary to assure

the validity of data and to ensure the ethical, scientific and technical quality of studies.

Data collected from studies designed, conducted, monitored, recorded, audited, analyzed

and reported in accordance with this guidance can be expected to facilitate the review

process since the regulatory authorities can have confidence in the integrity of studies

which follow such pre-established written procedures.

2.3. By following such pre-established written procedures, it is likely that

sponsors can avoid unnecessary repetition of definitive studies. Any requirement for local

effectiveness studies to confirm the findings of the definitive studies is not affected by this

guidance document. In addition, other guidance may exist which define study design and

effectiveness criteria for specific veterinary product categories. These studies also should

be conducted according to GCP principles.

2.4. Each individual involved in conducting a clinical study should be qualified by

education, training, and expertise to perform their respective task(s). These individuals

should demonstrate, in a manner that is evident from the study documentation, the highest

possible degree of professionalism in the recording and reporting of study observations.

2.5. The relevant regulatory authority should provide procedures that

independently assure that the study animals and the human and animal food chains are

protected. The relevant regulatory authority should also assure that informed consent has

been obtained from the owner of the study animals.

2.6. Studies covered by Good Laboratory Practice (GLP), basic exploratory 

studies or other clinical studies not intended to be used for regulatory support are not

included in the scope of this guidance. However, data derived from safety and pre-clinical

studies may be required to be submitted to the relevant regulatory authority in order that

subsequent clinical studies may be properly authorized prior to commencement.
Veterinary Services Memorandum No. 800.301 9

2.7. Wherever possible, investigational veterinary products should be prepared,

handled and stored in accordance with the concepts of good manufacturing practice (GMP)

of the relevant regulatory authorities. Details of preparation, handling and storage of

investigational veterinary products should be documented and the products should be used

in accordance with the study protocol.

2.8. The assurance of quality of every aspect of the study is a fundamental

component of sound scientific practices. The principles of GCP support the use of quality

assurance (QA) procedures for clinical studies. It is perceived that the sponsor would be

the party responsible for the QA functions for these studies. All participants in clinical

studies are encouraged to adopt and adhere to generally recognized sound QA practices.

IV. THE INVESTIGATOR (3)

3.1. General.

3.1.1. The investigator is the individual responsible for all aspects of the 

conduct of the study. These would include: the dispensing and the administration of

the investigational and control veterinary product(s), the implementation of the

study protocol, the collection and reporting of the study data and the protection of

the health and welfare of the personnel involved in the study and the animals during

the study.

3.1.2. The investigator should have sufficient knowledge, scientific training

and experience, as evidenced by a current curriculum vitae and other credentials, to

conduct clinical studies to investigate the effectiveness and in-use safety of

investigational veterinary products in the target species. The investigator should be

familiar with the background and requirements of the study before taking receipt of

the investigational veterinary product.

3.1.3. If a study is conducted by a group of individuals, the investigator is

the leader of the group.

3.1.4. The investigator may be assisted by trained competent staff in

collecting, recording and the subsequent processing of data.

3.1.5. An individual should not serve as both the investigator and the

monitor of any one study.

3.2. Responsibilities. The investigator should:

3.2.1. Submit to the sponsor, before the study is initiated, an up-to-date

personal curriculum vitae and other applicable credentials. 
Veterinary Services Memorandum No. 800.301 10

3.2.2. Agree, by signature, to the study protocol with the sponsor that the

study will be conducted according to the study protocol following the principles of

GCP and applicable regulatory requirements.

3.2.3. Ensure that the study is conducted according to the study protocol,

relevant SOPs, GCP and applicable regulatory requirements.

3.2.4. Maintain in the study documentation a signed and dated copy of the

study protocol which includes each study protocol amendment. Each study protocol

amendment, whether prepared by the sponsor or investigator, should be signed and

dated by the sponsor and investigator and should identify what has been changed or

modified and the reasons for such change or modification.

3.2.5. Record in a signed and dated statement, to be retained in the study 

documentation, any deviation from the study protocol and the reason for its

occurrence (if identifiable).

3.2.6. Notify the sponsor promptly of any study protocol deviation.

3.2.7. Provide sufficient qualified personnel, including (as appropriate) a

veterinarian to attend to the study animals, for the timely and proper conduct of the

study. Adequately inform and provide any necessary training to personnel involved

with the study or the management of the study animals to ensure compliance with

the study protocol and applicable regulatory requirements.

3.2.8. Delegate any authority and work, including any subcontracted work,

only to individuals qualified by training and experience to perform the assigned

duties.

3.2.9. Provide relevant materials and information obtained from the

sponsor to the study personnel.

3.2.10. Ensure that adequate and well-maintained facilities and equipment,

whether owned or leased, are used to conduct the study.

3.2.11. Utilize Standard Operating Procedures (SOPs) for practical

applications as appropriate.

3.2.12. Comply with applicable regulatory requirements governing the

humane care of study animals.
Veterinary Services Memorandum No. 800.301 11

3.2.13. Obtain informed consent from each owner, or owner’s agent, before

their animal(s) participate in the study. Each owner or owner’s agent should

receive relevant information regarding such participation from the investigator

prior to giving their consent.

3.2.14. Supervise the housing, feeding, and care of all study animals at the

study site and inform owners of animals housed off-site of their obligations as

stated in the study protocol.

3.2.15. Document any veterinary care and procedures, changes in animal

health, or significant environmental changes.

3.2.16. Comply with the study protocol regarding the use of edible

products derived from food-producing animals treated with an investigational and

control veterinary product(s) and the proper disposal of study animals.

3.2.17. Promptly notify the sponsor of adverse events (AEs).

3.2.18. Manage any code procedure and documentation (e.g. randomization

envelopes, blinding information) with professional care and ensure that any

treatment code is only broken in accordance with the study protocol and with the

sponsor’s knowledge and consent. Study personnel who can not be or are not

blinded (masked) should participate in the conduct of the study to the minimum

extent necessary.

3.2.19. Be responsible for the receipt, control, storage, distribution, and

further mixing with subsequent assay (if any) of the investigational and control

veterinary product(s) shipped or delivered to the investigator for the conduct of the

study.

3.2.20. Provide secure storage of, and control the access to the

investigational and control veterinary product(s) in accordance with the study

protocol and label specifications.

3.2.21. Maintain a full inventory of receipt, usage, assay results for the

investigational and control veterinary product(s) in feed or water (if further mixing

by the investigator is required) and any remaining stocks of unused investigational

and control veterinary product(s).

3.2.22. Ensure that the investigational and control veterinary product(s) are

dispensed and administered to study animals in accordance with the study protocol.
Veterinary Services Memorandum No. 800.301 12

3.2.23. Not redistribute the investigational and control veterinary

product(s) to any individual not authorized to receive them.

3.2.24. At the end of the study, reconcile delivery records of the

investigational and control veterinary product(s) with those of usage and returns

including accounting for any discrepancies.

3.2.25. When the study is completed or discontinued, be responsible for

and adequately document the safe and final disposal of the investigational and

control veterinary product(s), including animal feed containing the investigational

or control veterinary product(s). This may be achieved by return to the sponsor or

other appropriate means of disposal.

3.2.26. Collect and retain the study documentation.

3.2.27. Document unanticipated events that may affect the quality and

integrity of the study when they occur and any corrective action taken.

3.2.28. Collect and record data, including unanticipated observations, in

accordance with the study protocol and applicable regulatory requirements in an

unbiased manner that accurately and completely reflects the observations of the

study.

3.2.29. Prepare and maintain an accurate and complete record of all

contacts including all telephone calls, visits, letters, and other contacts with

representatives of the sponsor, representatives of relevant regulatory authorities

and other personnel (e.g., contract research organization personnel) concerning the

design, conduct, documentation, and reporting of the study. A contact record should

include: the date and time of the contact; the nature of the contact; the name and

organizational affiliation of all individuals involved; a summary of the purpose of

the contact and subject matter discussed with sufficient detail to describe the basis

of any actions that may be taken by the investigator and/or the sponsor as a result of

the contact.

3.2.30. Ensure that all specimens required to be retained by the study

protocol and any applicable regulatory requirements are identified in a manner that

is complete, accurate, legible and precludes loss of identification from the

specimen.

3.2.31. Securely store, protected from deterioration, destruction,

tampering, or vandalism, all study documentation or authenticated copies of study 
Veterinary Services Memorandum No. 800.301 13

documentation required to be retained by the investigator for the period of

time required by the relevant regulatory authorities.

3.2.32. Provide to the sponsor on request either the signed study

documentation or an authenticated copy. When all or part of the study

documentation is forwarded to the sponsor, an authenticated copy of the forwarded

information should be retained by the investigator.

3.2.33. Participate, when applicable, in the preparation of the final study

report.

3.2.34. Permit monitoring and quality auditing of a clinical study.

3.2.35. Permit the relevant regulatory authority to inspect the facilities used

by the investigator for the study and to inspect and copy any or all of the study

documentation made or kept by the investigator as part of or pertaining to the study

for the purpose of verifying the validity of the data.

V. THE SPONSOR (4)

4.1. General. An individual, company, institution or organization which takes

responsibility for the initiation, management, and financing of a clinical study for the

veterinary product under investigation.

4.2. Responsibilities. The sponsor should:

4.2.1. Ascertain that sufficient scientifically valid information exists with

respect to the effectiveness and safety of the investigational veterinary product to

justify conduct of the clinical study. The sponsor should also determine from this

information that there are no environmental, welfare, ethical or scientific grounds

which might preclude the conduct of a clinical study.

4.2.2. Ensure that notification or application relating to the conduct of the

study has been submitted to the regulatory authorities where required.

4.2.3. Select the investigator(s) and assure their qualifications, determine

their availability for the entire duration of the study, confirm that they agree to

undertake the study in accordance with an agreed study protocol, GCP and

applicable regulatory requirements.

4.2.4. Appoint appropriately qualified and trained monitor(s).
Veterinary Services Memorandum No. 800.301 14

4.2.5. Arrange, as necessary, for the preparation of SOPs for the

procedural and technical elements of the study.

4.2.6. Prepare a study protocol, in consultation with the investigator as

appropriate, giving due regard to the above considerations and consistent with the

principles for GCP.

4.2.7. Sign, along with the investigator, the study protocol as an agreement

that the clinical study will be conducted according to the study protocol. Any

amendments to the study protocol should have the signed agreement of both sponsor

and investigator.

4.2.8. Ensure, for multicenter studies, that:

4.2.8.1. All investigators conduct the study in strict compliance

with the study protocol agreed to by the sponsor and if required, by the

regulatory authority.

4.2.8.2. The data capture system is designed to capture the required

data at all multicenter study sites. For those investigators who are

collecting additional data requested by the sponsor, supplemental data

capture systems should be provided and designed to capture the additional

data.

4.2.8.3. All investigators are given uniform instructions on

following the study protocol, on complying with a uniform set of standards

for the assessment of clinical and laboratory findings and on capturing data.

4.2.8.4. Communication between investigators is facilitated.

4.2.9. Inform the investigator of appropriate chemical, pharmaceutical,

toxicological, safety, effectiveness and other relevant information as a prerequisite

to conducting the study. The sponsor should also inform the investigator of any such

pertinent information that becomes available during the study and when required,

ensure that the relevant regulatory authority is also notified.

4.2.10. Report all AEs in accordance with applicable regulatory

requirements.

4.2.11. Ensure the proper disposal of all study animals and any edible

products derived from them according to the applicable regulatory requirements.
Veterinary Services Memorandum No. 800.301 15

4.2.12. Ensure that the investigational and control veterinary product(s)

have been prepared, labeled and shipped according to requirements of the relevant

regulatory authority.

4.2.13. Prepare and retain records of shipment of the investigational

veterinary and control product(s). When the study is completed or discontinued,

ensure the proper and final disposal of all supplies of the investigational and

control veterinary product(s) and any animal feed containing the investigational or

control veterinary product.

4.2.14. Maintain study documentation, protected from deterioration,

destruction, tampering or vandalism, for as long as required to fulfill applicable

regulatory requirements in the countries where the study has been submitted in

support of the registration of the investigational veterinary product.

4.2.15. In the event that an animal is treated with an investigational

veterinary product, arrange for a study report to be written whether or not the study

has been completed as planned.

4.2.16. Ensure the quality and integrity of data from clinical studies by

implementing quality audit procedures that are consistent with well-recognized and

accepted principles of quality assurance.

4.2.17. Comply with the applicable regulatory requirements governing the

humane care of study animals.

4.3. Delegations to a CRO.

4.3.1. A sponsor may delegate any or all of the sponsor’s study-related

duties and functions to a CRO, but the ultimate responsibility for the quality and

integrity of the study data always resides with the sponsor.

4.3.2. Any study-related duty or function that is delegated to a CRO should

be specified in writing. The sponsor should notify the CRO of its responsibility to

comply with applicable regulatory requirements.

4.3.3. Any study-related duties or functions not specifically delegated to a

CRO are retained by the sponsor.

4.3.4. All references to a sponsor in this guidance also apply to a CRO to

the extent that a CRO has assumed the study-related duties and functions of a

sponsor. 
Veterinary Services Memorandum No. 800.301 16

VI. THE MONITOR (5)

5.1. General. An individual appointed by the sponsor to be responsible to the

sponsor for monitoring and reporting on progress of the study, verifying the data and

confirming that the clinical study is conducted, recorded and reported in compliance with

GCP and applicable regulatory requirements. The monitor should have scientific training

and experience to knowledgeably oversee a particular study. The monitor should be trained

in quality control techniques and data verification procedures. The monitor should

understand all applicable protocol requirements and be able to determine whether the study

was conducted in accordance with the protocol and relevant SOPs. An individual should

not serve as both the monitor and investigator for any one study. The monitor is the

principal communication link between the sponsor and the investigator.

5.2. Responsibilities. The monitor should:

5.2.1. Assist the sponsor to select the investigator when requested.

5.2.2. Be reasonably available to the investigator for consultation in

person, by telephone or by other means.

5.2.3. Determine that the investigator and staff have sufficient time to

devote to the study. Also, determine that the study site has adequate space,

facilities, equipment and staff and that an adequate number of study animals is

likely to be available for the duration of the study.

5.2.4. Confirm that the study staff has been adequately informed about the

details of the study.

5.2.5. Ensure that the investigator accepts responsibility for conducting the

study and in so doing understands: the investigational status of the veterinary

product under evaluation; the nature and details of the study protocol; the

applicable regulatory requirements governing the humane care of study animals; the

conditions of any authorization for the use of edible products derived from

food-producing animals treated with the investigational or control veterinary

product(s) and any other applicable restrictions on the disposal or subsequent use

of study animals.

5.2.6. Work according to the sponsor’s requirements, visit the investigator

with sufficient frequency before, during and after the study to control adherence to

the study protocol, GCP and applicable regulatory requirements.
Veterinary Services Memorandum No. 800.301 17

5.2.7. Not, in any way, bias the data collection process or outcome of the

study, other than to ensure that the current study protocol, relevant SOPs, GCP and

applicable regulatory requirements are being followed.

5.2.8. Ensure that informed consent is obtained and recorded from the

owner(s) or owner’s agents prior to their animals participating in the study.

5.2.9. Ensure that all data are correctly and completely recorded.

5.2.10. Ensure that illegible, missing or corrected study documentation is

fully explained.

5.2.11. Confirm that the storage, dispensing and documentation of the

supply of the investigational and control veterinary product(s) are safe and

appropriate and ensure that any unused products are returned by the investigator to

the sponsor or disposed of properly.

5.2.12. Review the raw data and other study documentation necessary to

determine that the study protocol is being followed and the information maintained

or kept by the investigator is accurate and complete.

5.2.13. Prepare and maintain an accurate and complete record of all

contacts including all telephone calls, visits, letters and other contacts with the

investigator, representatives of the sponsor, representatives of relevant regulatory

authorities and other personnel (e.g., contract research organization personnel)

concerning the design, conduct, documentation, and reporting of the study. A contact

record should include: the date and time of the contact; the nature of the contact; the

name, and organizational affiliation of all individuals involved; a summary of the

purpose of the contact and subject matter discussed with sufficient detail to

describe the basis of any actions that may be taken by the investigator and/or the

sponsor as a result of the contact.

5.2.14. Confirm investigator compliance to the principles of GCP by

providing a signed and dated summary report of the contacts, visits made and

activities witnessed during the conduct of the study. This summary report should be

submitted to the sponsor at the end of the study.
Veterinary Services Memorandum No. 800.301 18

VII. THE STUDY PROTOCOL (6)

6.1. General.

6.1.1. A study protocol is a document that states the objectives of the study

and defines the conditions under which the study is to be performed and managed.

6.1.2. A well-designed study relies predominantly on a thoroughly

considered, well-structured and comprehensive protocol which should be

completed and approved by the sponsor and investigator before the study is

initiated.

6.1.3. A comprehensive study protocol that is easily understood by the

investigator executing the study and by the relevant regulatory authority reviewing

the protocol and study results may facilitate the registration process for veterinary

products.

6.2. Study Protocol Review. Review of the study protocol by the relevant 

regulatory authority prior to the initiation of the clinical study is encouraged within the

principles of GCP particularly when there is any uncertainty about a proposed study design

or there are differing opinions about the relevance of several options for conducting the

study. Review of the study protocol by the relevant regulatory authority does not bind the

authority to accept the data collected from a study conducted using such a study protocol.

However, it is expected that both the sponsor and the relevant regulatory authority would

benefit from such a review, in terms of a mutual understanding of the regulatory

requirements and the relevance of the objective(s) of the study protocol.

6.3. Study Protocol Check List. The study protocol should contain the 

information given in the following list of items or this list should be considered whenever

a study is contemplated. The list provided is not exhaustive nor is every item included

applicable to all study protocols but it is intended to give guidance:

6.3.1. Title of the study.

6.3.2. Identifier unique to the study. A unique identifier consists of a study

protocol number, the status of the study protocol (i.e., draft, final, amended) and the

date of the version of the study protocol, all of which should be clearly located on

the title page.

6.3.3. Study contacts. Study contacts include the investigator,

representatives of the sponsor and all other participants responsible for major 
Veterinary Services Memorandum No. 800.301 19

aspects of the study. List, for each contact, the title, qualifications, professional

background, as well as the postal address telephone number and other

communication means.

6.3.4. Identity of the sites (if known at the time of study protocol 

preparation).

6.3.5. Objective(s)/purpose of the study.

6.3.6. Justification. Describe all information where relevant to the

understanding of the objective of the study (pre-clinical or clinical data published

or otherwise available) that justifies the conduct of the clinical study.

6.3.7. Schedule of events. Schedule of key events occurring during the

animal phase of the study including: the expected date and time of commencement

of the animal phase, the period during which the investigational and control

veterinary product(s) are being administered, the post administration observation

period, the withholding period (when applicable) and the termination date where

known .

6.3.8. Study design. Describe:

6.3.8.1. The overall design of the study, e.g. a placebo control

clinical field effectiveness study or a randomized blocked design versus a

positive control, with blinding.

6.3.8.2. The treatment, if any, in detail to be applied to control

group(s) or for control period(s).

6.3.8.3. The randomization method, including the procedures to be

adopted and practical arrangements to be followed to allocate animals to

treatment groups and treatment groups to experimental units.

6.3.8.4. The experimental unit(s) and justify their selection.

6.3.8.5. The extent and methods of blinding (masking) and other

bias reducing techniques to be used and state the provisions, including

procedures and personnel, for access to treatment codes.

6.3.9. Animal selection and identification. Specification of the source,

number, identity and type of study animal to be used, such as species, age, gender,

breed category, weight, physiological status and prognostic factors. 
Veterinary Services Memorandum No. 800.301 20

6.3.10. Inclusion/exclusion and post-inclusion removal criteria. Specify

objective criteria for the exclusion from, inclusion in and removal subsequent to

inclusion in the study.

6.3.11. Animal management and housing. Describe:

6.3.11.1. The containment of the study animals, e.g. pens, kennels,

pastures.

6.3.11.2. Space allocation per animal (in comparison to standard

management practices).

6.3.11.3. The thermoregulation (heating/cooling) and ventilation of

animal accommodation.

6.3.11.4. Permissible and non-permissible concomitant veterinary

care and therapy.

6.3.11.5. The management of feed (including pasture management

and the preparation and storage of mixed feeds) and water (including

supply, availability and quality) and their presentation to the study animals.

6.3.12. Animal feeds. Authoritative reference sources may serve as useful

guides in the determination of the nutritional requirements of the study animals and

preparation of feeds. The ration-related study documentation should be sufficient to

establish that the nutritional requirements of the animals are met so as not to

compromise the objectives of the study and to ensure that animal welfare

requirements are met. Where nutritional status can be critical to the measurements

to be collected in the study, detailed records of feed characteristics should be

collected. As appropriate:

6.3.12.1. Determine the nutrient needs of the study animals and

prepare feeds meeting these needs.

6.3.12.2. Provide quantitative composition (e.g., feedstuffs,

vitamins, minerals and, as appropriate, permissible feed additives) and

calculated nutrient densities for all feeds used in the study.

6.3.12.3. Describe procedures for the sampling of the feed used in

the study and subsequent analysis of these samples for selected nutrients.
Veterinary Services Memorandum No. 800.301 21

6.3.12.4. Develop and follow objective criteria to determine

whether feeds used in the study, based on actual laboratory nutrient

analyses, meet the pre-determined calculated requirements.

6.3.12.5. Provide a feeding program (feeding schedule).

6.3.12.6. Collect records of the amount of feed offered and refused.

6.3.13. Investigational veterinary and control product(s).

6.3.13.1. Clearly and precisely identify the investigational

veterinary product to readily permit an unambiguous determination of the

specific formulation. Instructions for the further mixing (if any), packaging

and storage of these products should be stated.

6.3.13.2. If the investigational veterinary product is administered in

feed or water, describe the procedures for determining the concentration of

the investigational veterinary product in the feed or water, including the

sampling methods and assay methodologies (e.g. laboratory used, analytical

method, number of replicates, assay limits, permitted analytical variation)

to be used. Develop and follow objective criteria to determine whether the

investigational veterinary product concentration in the feed or water is

adequate.

6.3.13.3. Identify control products by generic or trade name; dosage

form, formulation (ingredients); concentration; batch number; expiry date.

Store and use these products according to label directions.

6.3.14. Treatments. For the investigational and control veterinary

product(s):

6.3.14.1. Justify the dosing to be used.

6.3.14.2. Describe the dosing regimen (route, site of injection,

dose, frequency and duration of administration) to be followed in

administering the products.

6.3.14.3. Specify objective criteria for the potential use of

concomitant veterinary treatment.

 
Veterinary Services Memorandum No. 800.301 22

6.3.14.4. Describe the methods and precautions to be taken to

ensure the safety of study personnel handling these products prior to and

during administration.

6.3.14.5. Describe measures to ensure administration of these

products in compliance with the study protocol or its labeling.

6.3.15. Disposal of study animals, products of study animals and

investigational and control veterinary product(s).

6.3.15.1. Describe the proposed disposal of the study animals.

6.3.15.2. Describe the care to be given to animals removed from the

study in accordance with pre-established criteria.

6.3.15.3. State the conditions for use of edible products from

food-producing animals that must be followed in order to comply with the

authorization granted by the relevant regulatory authority.

6.3.15.4. Describe the proposed disposal of the investigational and

control veterinary product(s).

6.3.16. Assessment of effectiveness.

6.3.16.1. Define the effects to be achieved and the clinical

end-point(s) to be reached before effectiveness can be claimed.

6.3.16.2. Describe how such effects and end-points are to be

measured and recorded.

6.3.16.3. Specify the timing and frequency of study observations.

6.3.16.4. Describe the special analyses and/or tests to be performed

including the time of sampling and the interval between sampling, storage of

samples, and the analysis or testing.

6.3.16.5. Select and define any scoring system and measurements

that are necessary to objectively measure the targeted response(s) of the

study animal and evaluate the clinical response.

6.3.16.6. Define the methods for computing and calculating the

effect of the investigational veterinary product. 
Veterinary Services Memorandum No. 800.301 23

6.3.17. Statistics/Biometrics. Thoroughly describe the statistical

methodologies to be used to evaluate the effectiveness of the investigational

veterinary product, including the hypotheses to be tested, the parameters to be

estimated, the assumptions to be made and the level of significance, the

experimental unit and the statistical model to be used. The planned sample size

should be justified in terms of the target animal population, the power of the study

and pertinent clinical considerations.

6.3.18. Handling of records. Specify procedures for recording, processing,

handling, and retaining raw data and other study documentation required by the

relevant regulatory authority.

6.3.19. Adverse events. Describe procedures for:

6.3.19.1. Observing study animals with sufficient frequency to

detect AEs.

6.3.19.2. Taking appropriate actions in response to observed AEs.

Appropriate actions may involve, among other items, locating and breaking

blinding codes so that appropriate medical treatment can be given.

6.3.19.3. Recording of the AEs in the study documentation.

6.3.19.4. Reporting AEs to the sponsor.

6.3.20. Supplements to be appended to the protocol.

6.3.20.1. List any study-specific SOPs that apply to the conduct,

monitoring and reporting of the study.

6.3.20.2. Attach a copy of all data capture and event record forms

to be used during the study.

6.3.20.3. Include any other relevant supplements, e.g. Information to

be provided to the owners of animals, instructions to study personnel.

6.3.21. Changes to the study protocol. Instructions for preparation of

amendments and reporting of deviations to the study protocol should be provided.

6.3.22. References. Provide citations to relevant literature referenced in

the study protocol.

 
Veterinary Services Memorandum No. 800.301 24

VIII. THE FINAL STUDY REPORT (7)

7.1. General.

7.1.1. The final study report (FSR) is a complete and comprehensive

description of the study written after its completion. It includes a description of the

materials and methods, a presentation and evaluation of the results, statistical

analyses and a critical clinical, scientific and statistical appraisal. The report

should follow the format of the study protocol.

7.1.2. It is the responsibility of the sponsor to provide a FSR for any study

in which an animal has been treated with an investigational veterinary product

whether or not the study has been completed as planned.

7.2. Authorship.

7.2.1. The preparation of this report can be accomplished as follows:

7.2.1.1. The sponsor may prepare the FSR;

7.2.1.2. The investigator may prepare the FSR for the sponsor; or

7.2.1.3. The sponsor and investigator may prepare the FSR through

a collaborative effort.

7.2.2. All individuals involved in the preparation of the FSR would be

considered author(s).

7.2.3. When an investigator relinquishes authorship of the FSR, the

investigator should provide to the authors:

7.2.3.1. All necessary study documentation specific to the site at

which the investigator conducted the study, and

7.2.3.2. A signed and dated document, to be included in the FSR,

which adequately describes the study documentation provided to the

author(s) and attests to the accuracy and completeness of the documentation

provided.

7.2.4. The authors of the FSR should sign and date the report. Authors of

the FSR should be aware that the regulatory authorities view these signatures as an

affirmation that all data were collected in compliance with the study protocol, 
Veterinary Services Memorandum No. 800.301 25

relevant SOPs, GCP and applicable regulatory requirements and that all statements are

accurate and complete representations of study activities and results and are fully

supported by the study documentation. Therefore, the authors may wish to include in the

report a brief statement describing their contributions to the report.

7.3. Content of Final Study Report. The FSR should include relevant information

from the following list. The list provided is not exhaustive nor is every item included

applicable to all FSRs but it is intended to give guidance. The study protocol section

should be consulted for an explanation of the items in this list.

7.3.1. Title and identifier of the study.

7.3.2. Objectives of the study.

7.3.3. The titles, names, qualifications and roles of all people involved

in conducting key elements of the study.

7.3.4. The identity of the site(s) at which the study was conducted.

7.3.5. Key study dates.

7.3.6. Materials and methods.

7.3.6.1. Study design.

7.3.6.2. Animal selection and identification.

7.3.6.2.1. Full details of study animals in each group,

including but not limited to: numbers, breed, age, gender and

physiological status.

7.3.6.2.2. Disease history of the animals, where available 

and if appropriate, relevant to the condition under investigation,

especially in the case of specific disease problems associated with

an animal unit.

7.3.6.2.3. Where appropriate, diagnosis of the condition

being treated or prevented, including a description of the clinical

signs or other diagnostic methods according to conventional criteria.
Veterinary Services Memorandum No. 800.301 26

7.3.6.2.4. Detailed inclusion and exclusion criteria applied

to the selection of study animals.

7.3.6.2.5. Full information on any study animal removed

subsequent to inclusion in the study.

7.3.6.3. Animal management and housing.

7.3.6.3.1. Details of animal housing and management.

7.3.6.3.2. Composition of feed and the nature and quantity

of any additives in the feed.

7.3.6.3.3. Details of any concomitant treatment administered

during the study, either prior to, during or after treatment with the

investigational veterinary or control product(s) and details of any

interactions observed.

7.3.6.4. Animal disposal. A summary of the disposal of the study

animals and their edible products.

7.3.6.5. Treatments.

7.3.6.5.1. The identification of the study investigational

formulation used in the study including strength, purity, composition,

quantity and batch or code mark.

7.3.6.5.2. The dosage of the investigational veterinary

product, method, route and frequency of administration and

precautions, if any, taken during administration.

7.3.6.5.3. Details of the control product(s) used with a

justification for their selection.

7.3.6.5.4. The duration of treatment and observation

periods.

7.3.6.5.5. A summary of use and disposal of all

investigational veterinary product and control product(s) shipped or

delivered to the investigator.
Veterinary Services Memorandum No. 800.301 27

7.3.6.6. Study procedures. A full description of the methods used

including, if applicable, assay methods used to determine investigational

veterinary product concentration in feed, water, body fluids and tissues.

7.3.6.7. Statistical methods. A description of the transformations,

calculations or operations performed on the raw data and any statistical

methods employed to analyze the raw data. Reasons should be given if the

statistical methods used differed from those proposed in the study protocol.

7.3.7. Results and their evaluation. A full description of the results of the

study, whether favorable or unfavorable, including tables of all data recorded

during the study.

7.3.8. Conclusions based on each individual case or treatment group as

appropriate.

7.3.9. Administrative and compliance items.

7.3.9.1. A description of the procedures used to record, process,

handle and retain raw data and other study documentation.

7.3.9.2. A description of any protocol deviations and/or

amendments and an assessment of their impact on the outcome of the study.

7.3.9.3. A description of circumstances that could have affected the

quality or integrity of the data, specifying the time frame and the extent of

their occurrence.

7.3.9.4. Details of any AEs occurring during the study and any

measures taken in consequence. For all studies where no AE was observed

or recorded a statement to this effect should be included in the FSR.

7.3.9.5. The location of all study documentation.

7.3.10. Additional information. Additional information such as the

following may be included in the body of the report or as an appendix:

7.3.10.1. Study protocol

7.3.10.2. Dates of monitoring visits
Veterinary Services Memorandum No. 800.301 28

7.3.10.3. Audit certification by auditor, consisting of the dates of

site visits, audits, and when reports were provided to the sponsor.

7.3.10.4. Supplementary reports, e.g. analytical, statistical, etc.

7.3.10.5. Copies of study documentation supporting study

conclusions

7.4. Report Amendments. Any addition, deletion, or correction 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, deleted or corrected and the reasons for the change(s)

and should be signed and dated by the authors. Minor errors, e.g. typographical errors,

noted after finalization of the report may be indicated directly on the FSR when

accompanied by the signature or initials of the authors, the date of the change and the

reason for the change.

IX. STUDY DOCUMENTATION (8)

8.1. General.

8.1.1. Study documentation consists of those records that individually and

collectively permit evaluation of the conduct of the study and the quality of the data

produced. Filing study documentation, or authenticated copies thereof, at the

investigator and sponsor sites in a timely manner can greatly assist in the successful

management of a study by the investigator and sponsor.

8.1.2. All study documentation should be retained for the period of time

required by relevant regulatory authorities. Any or all of the study documentation

described in this guidance is subject to, and should be available for monitoring on

behalf of the sponsor. Study documentation should be audited by the sponsor’s

quality audit procedures, consistent with well-recognized and accepted principles

of quality assurance. When a quality audit is conducted, the auditor should prepare

a report for the sponsor which details the auditing process and which certifies that

the audit has been conducted.

8.1.3. Any or all of the study documentation described in this guidance may

be inspected, audited and copied by the relevant regulatory authority as part of the

process to confirm the validity of the study conduct and the integrity of the data

collected.

8.1.4. The requirements for the submission of study documentation should

be governed by the relevant regulatory authority. 
Veterinary Services Memorandum No. 800.301 29

8.2. Categories of study documentation. Study documentation includes, but is

not limited to:

8.2.1. Study protocol. This documentation consists of the original study

protocol, all protocol amendments and records of all protocol deviations.

8.2.2. Raw data. The raw data of a study generally includes several classes

of data. Neither the classes below nor the examples provided for each class are

intended to be all-inclusive.

8.2.2.1. Animal records. All pertinent data relating to the study

animals, such as: purchase records, documentation of animal exclusion

from, inclusion in and removal subsequent to inclusion in the study, 

informed consent of the owner, treatment assignment, all recorded

observations (including analytical assay results of biological samples),

case report forms, adverse events, animal health observations, composition

and nutrient assay of animal feeds and final animal disposal.

8.2.2.2. Investigational and control veterinary product records. All

pertinent records of the ordering, receipt, inventory, assay, use or

administration (documenting the dosing regimen, e.g. dose, rate, route, and

duration of administration), return, and/or disposal of all the investigational

and control veterinary product(s) including any animal feed containing the

investigational or control veterinary product.

8.2.2.3. Contact records. The monitor’s and investigator’s records

of all contacts (e.g. visits, telephone, written and electronic) relating to the

design, conduct, documentation, and reporting of a study.

8.2.2.4. Facility and equipment records. As appropriate,

descriptions of the study site, e.g. diagrams and photographs, equipment

identification and specifications, equipment calibration and maintenance

records, equipment failure and repair records, meteorological records and

environmental observations.

8.2.3. Reports. Reports consist of:

8.2.3.1. Safety reports. Reports of adverse events.

8.2.3.2. Final study report.
Veterinary Services Memorandum No. 800.301 30

8.2.3.3. Other reports. For example, statistical, analytical, and 

laboratory reports.

8.2.4. Standard operating procedures and reference materials. These

include any reference materials and SOPs related to key elements of the study.

8.3. Recording and handling study documentation.

8.3.1. Raw data, whether handwritten or electronic, should be attributable, 

original, accurate, contemporaneous and legible. Attributable means the raw data

can be traced by signature (or initials) and date to the individual who observed and

recorded the data. If more than one individual observes or records the raw data,

that fact should be reflected in the data entries. In automated data collection

systems, the individual(s) responsible for direct data input should record their

name along with the date at the time of data input. Original and accurate means the

raw data are the firsthand observations. Contemporaneous means the raw data are

recorded at the time of observation. Legible means the raw data are readable and

recorded in a permanent medium, e.g. ink for written records or electronic records

that are unalterable.

8.3.2. Raw data should be maintained in an organized manner and, where 

appropriate, should be recorded in a bound laboratory notebook or on

pre-established forms designed specifically for recording particular

observation(s). Records should be diligently completed with all data points

recorded as required in the study protocol. When additional observations are

warranted, e.g. to provide additional information for pre-planned observations or

observation of unanticipated events, such observations should also be recorded.

8.3.3. Units used to measure observations should always be stated and

transformation of units should always be indicated and documented. Values of

laboratory analyses should always be recorded on a record sheet or attached to it.

If available, normal reference values for the laboratory analyzing the specimens

should be included.

8.3.4. If a portion of the raw data needs to be copied or transcribed for

legibility, an authenticated copy of that data should be made. The reason for the

copying or transcription should be explained in a dated memorandum or in a dated 

notation on the transcribed record, signed by the individual(s) making the copy or

transcription. In such a case the copied raw data, the copy or transcript of the raw

data and the memorandum should be kept together in the study documentation.
Veterinary Services Memorandum No. 800.301 31

8.3.5. Any correction in the hand-written study documentation should be

made by drawing one straight line through the original entry. The original entry

should still be legible. The correction should be initialed and dated by the

individual(s) making the correction at the time the correction is made and should

describe the reason for the change.

8.3.6. Similarly, if data are entered directly into a computer system, the

electronic record is considered the raw data. A computerized system should ensure

that the methods for record keeping and retention afford at least the same degree of

confidence as that provided with paper systems. For example, each entry,

including any change, should be made under the electronic signature of the

individual making the entry, and any changes that are made to data stored on

electronic media should be maintained in an audit trail to protect the authenticity

and integrity of the electronic records.

8.4. Retention of study documentation.

8.4.1. All study documentation should be stored in a manner that protects it

from deterioration, destruction, tampering or vandalism in accordance with the

nature of the records. The storage site should permit the orderly storage and easy

retrieval of the retained documentation.

8.4.2. The location of the study documentation, and any authenticated copy,

for a study should be specified in the final study report.

8.4.3. All study documentation should be retained for an appropriate

period of time to satisfy the requirements of the relevant regulatory authorities to

which the study may be or has been submitted in support of the registration of the

investigational veterinary product.

 /s/

Alfonso Torres

Deputy Administrator

Veterinary Services