#254 
 
Donor Eligibility for Animal Cells, 
Tissues, and Cell- and Tissue-Based 
Products 
 
Guidance for Industry 
 
Submit comments on this guidance at any time.  Submit electronic comments to 
https://www.regulations.gov.  Submit written comments to the Dockets Management Staff 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD  
20852.  All comments should be identified with docket number FDA-2021-D-0401. 
 
For further information regarding this document, contact AskCVM@fda.hhs.gov. 
 
Additional copies of this guidance document may be requested from the Policy and Regulations 
Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish 
Place, Rockville, MD 20855, and may be viewed on the Internet at https://www.fda.gov/animal-
veterinary, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or 
http://www.regulations.gov. 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
October 2022 Contains Nonbinding Recommendations 
Table of Contents 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  PURPOSE AND SCOPE .................................................................................................. 2 
IV.  DONOR ELIGIBILITY DETERMINATION ............................................................... 3 
A.  General ......................................................................................................................... 3 
B.  Submitting Donor Selection Criteria and Donor Eligibility Determinations to 
CVM ............................................................................................................................. 3 
C.  Relevant Disease Agents ............................................................................................. 5 
D.  Donor Screening .......................................................................................................... 6 
E.  Donor Testing .............................................................................................................. 8 
F.  Final Donor Eligibility Determination .................................................................... 11 
V.  PROCEDURES ............................................................................................................... 12 
VI.  DONOR TRACKING ..................................................................................................... 12 
VII.  RECORDS ....................................................................................................................... 12 
A.  Record maintenance and retention ......................................................................... 12 
B.  Records accompanying the ACTP ........................................................................... 13 
VIII.  QUARANTINE OF ACTPS........................................................................................... 14 
IX.  ACTPS FROM INELIGIBLE DONORS ..................................................................... 14 
i 
  Contains Nonbinding Recommendations 
Donor Eligibility for Animal Cells, Tissues, and Cell- and Tissue-
Based Products 
 
Guidance for Industry 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. 
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.  
 
I.  INTRODUCTION 
This guidance is for sponsors, firms, individuals, and establishments that participate in the 
manufacture of, or perform any aspect of the donor eligibility determination for animal cells, 
tissues, and cell- and tissue-based products (ACTPs).  ACTPs that are intended for use in the 
diagnosis, cure, mitigation, treatment, or prevention of disease or ACTPs intended to affect the 
structure or function of the animal generally meet the definition of a new animal drug.1  All new 
animal drugs, including ACTPs, are required to be manufactured in accordance with Current 
Good Manufacturing Practice (CGMP) to ensure that such drugs meet the requirements of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) as to safety, and have the identity, strength, 
quality, and purity characteristics which they purport to or are represented to possess.2  Donor 
eligibility is critical to ensuring safety and quality when manufacturing allogeneic or xenogeneic 
ACTPs.  A donor of allogeneic or xenogeneic ACTPs should be considered eligible to donate 
only if screening of the donor shows that the donor is healthy and free from risk factors for, and 
clinical evidence of, infection with relevant disease agents and diseases, and the donor (and 
product/source material) test results for relevant disease agents are negative or nonreactive. 
 
The Food and Drug Administration (FDA, or we) encourages sponsors and manufacturers of 
ACTPs (you) to contact CVM early in product development to discuss considerations specific to 
the manufacture and approval of your new animal drug product. 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidance means that something is suggested or recommended, but 
not required. 
 
 
1 Section 201(v) of the FD&C Act [21 U.S.C.  321(v)] defines a new animal drug, in part, as any drug intended 
for use for animals that is not generally recognized as safe and effective for use under the conditions prescribed, 
recommended, or suggested in the drugs labeling. 
2 See section 501(a)(2)(B) of the FD&C Act [21 U.S.C.  351(a)(2)(B)] 
1  Contains Nonbinding Recommendations 
II.  BACKGROUND 
Advances in the field of veterinary regenerative medicine have resulted in increasing research 
into veterinary applications for ACTPs, and many of these products are intended for use as new 
animal drugs.  
 
In this guidance, ACTPs mean those articles containing, consisting of, or derived from cells or 
tissues that are intended for implantation, transplantation, infusion, transfer, or other means of 
administration to an animal recipient.  In this guidance, the term ACTP refers only to those 
products subject to regulation under the FD&C Act.  ACTPs include cell-based products and 
animal stem cell-based products as defined in Guidance for Industry (GFI) #218, Cell-Based 
Products for Animal Use (July 2015).3 
 
This guidance offers FDAs recommendations for those aspects of manufacturing related to 
determining donor eligibility for ACTPs.  There are both statutory and regulatory requirements 
for CGMP.  The CGMP statutory requirements are found in section 501(a)(2)(B) of the FD&C 
Act.  The CGMP regulatory requirements are found in Title 21 of the Code of Federal 
Regulations, parts 210 and 211.   
 
As noted in GFI #253, Current Good Manufacturing Practice for Animal Cells, Tissues, and 
Cell- and Tissue-Based Products (October 2022),4 FDA recognizes that the manufacture of 
ACTPs presents unique considerations for complying with regulatory CGMP including donor 
eligibility determinations.  Establishments may use an alternative approach if it satisfies the 
requirements of section 501(a)(2)(B) of the FD&C Act and applicable regulations.  
 
Selecting appropriate donors is critical to ensuring the safety, identity, strength, quality, and 
purity of the resulting product.  This guidance addresses appropriate methods and considerations 
for determining donor eligibility for ACTPs intended for use as new animal drugs.  
Establishments performing any function related to donor eligibility should comply with the 
CGMP related to that function. 
 
III.  PURPOSE AND SCOPE 
To prevent transmission of disease when manufacturing ACTPs, it is necessary to determine that 
donors are healthy and free from relevant disease agents (see section IV.C. Relevant Disease 
Agents for the definition of relevant disease agents).  Transmission of relevant disease agents by 
an ACTP can result from the presence of relevant disease agents in the donated cells/tissues 
(either within the cells/tissues, within other accompanying cells/tissues, or in the extracellular 
components of the product).   
 
This guidance provides recommendations for determining that a donor is healthy and free from 
relevant disease agents and is an eligible source of cells, tissues, or both, used in the manufacture 
of allogeneic or xenogeneic ACTPs.  The recommendations in this guidance are intended to help 
 
3 https://www.fda.gov/media/88925/download 
4 https://www.fda.gov/media/147150/download 
2  Contains Nonbinding Recommendations 
manufacturers of ACTPs ensure product safety and comply with the statutory and applicable 
regulatory CGMP requirements for the manufacture of new animal drugs.   
   
This guidance applies to sponsors, firms, individuals, and establishments that participate in the 
manufacture of ACTPs and perform any aspect of donor eligibility determination.     
 
IV.  DONOR ELIGIBILITY DETERMINATION 
A.  General 
The donor eligibility determination is a conclusion, based on donor screening and testing 
results, that a donor is either eligible or ineligible to donate cells or tissues for use in the 
manufacture of an ACTP.  The donor eligibility determination ensures that the donor is 
healthy and free from risk factors for, and clinical evidence of, relevant disease agents 
and diseases.  
 
A donor eligibility determination should be completed for each donation of cells or 
tissues used in the manufacture of an ACTP.  This includes all components of the ACTP 
of human or animal origin.  In general, the donor eligibility determination should be 
performed for the individual donor.  In the case of embryonic or fetal donations, a donor 
eligibility determination should be performed for both the oocyte donor and semen donor 
(and surrogate dam, if appropriate).  In the case of a closed group of animals, it may be 
possible to perform a donor eligibility determination for the entire group. 
 
The donor eligibility determination should be made by a person with appropriate training 
and qualifications, including adequate knowledge of applicable Federal regulations and 
guidance.  All information contributing to the donor eligibility determination should be 
documented and attributable to the person providing the information.  For example, a 
physical examination of a potential donor animal should be performed by a veterinarian.  
The veterinarian should record the results of the examination, and sign and date the 
record.  The veterinarians training and qualifications should also be documented. 
 
A donor should be considered eligible only if screening of the donor shows that the donor 
is healthy and free from risk factors for, and clinical evidence of, infection with relevant 
disease agents and diseases, and the donor (and product/source material) test results for 
relevant disease agents are negative or nonreactive.  
 
An ACTP should not be implanted, transplanted, infused, or transferred, until the donor 
has been determined to be eligible. 
 
B.  Submitting Donor Selection Criteria and Donor Eligibility Determinations to 
CVM 
There are two occasions when you should submit information relating to donor eligibility 
to CVM: 
 
  Donor selection criteria 
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You should submit your process and criteria for selecting donors to CVM for review 
early in the development process (before donors are selected).  This early submission 
should include items 1 through 6 from the list below.  Data collection forms 
associated with item 7 and considerations associated with item 10 should also be 
included in the submission.  Your process and criteria for selecting donors should be 
submitted to the donor eligibility module of the product characterization technical 
section of your Investigational New Animal Drug (INAD) file. 
  
A risk-based, product-specific approach should be used to determine the selection 
criteria for eligible donors.  The selection criteria should consider the characteristics 
of the product, the intended recipient population, the donor population, and the risk of 
transmission of disease agents to both recipients and persons handling the ACTP.  A 
combination of donor screening (historical and clinical information), donor testing 
(testing the donor for specific disease agents), and testing of the donated cells/tissue 
or product for specific disease agents should be used to demonstrate the absence of a 
disease agent in the donor.  For example, when donor screening information is not 
sufficient to ensure absence of a disease agent, testing of the donor or donated 
cells/tissues or product should be performed.  In combination with a comprehensive 
donor screening program, the most sensitive test method for detecting a disease agent 
should be utilized.  
 
  Donor eligibility determination  
 
After you have determined a donor to be eligible, you should submit the data 
supporting the donor eligibility determination to CVM for review prior to approval of 
the ACTP containing cells or tissue from that donation.  This submission should 
include items 6 through 10 from the list below, as well as any changes, deviations 
from, or new information pertaining to items 1 through 6.  The donor eligibility 
determination for donors of cells and tissues used to manufacture product that is the 
subject of an original new animal drug application may be submitted to the donor 
eligibility module of the product characterization technical section.  Donor eligibility 
determinations for new donations occurring after the original application is approved 
should be submitted as part of the prior-approval supplement supporting approval of 
the new cell line or source material.   
 
Information submitted to CVM in support of donor eligibility should include the 
following: 
1.  A list of relevant disease agents for your ACTP (see section IV.C. Relevant 
Disease Agents); 
2.  Your standard operating procedure(s) (SOP) or protocol for determining 
donor eligibility, including the specific criteria for determining a donor to be 
eligible; 
3.  Donor screening methods (see section IV.D. Donor Screening); 
4  Contains Nonbinding Recommendations 
4.  Testing methods for testing of the donor and donated cells/tissues or product 
(see section IV.E. Donor Testing); 
5.  Justifications, as needed, for inclusion/exclusion of agents from the list of 
relevant disease agents, donor screening, and testing methods and eligibility 
criteria;  
6.  Qualifications and training of the person responsible for determining donor 
eligibility; 
7.  Documentation for donor screening, testing, and donor eligibility 
determination, including all data collection forms and raw data; 
8.  Test method validation; 
9.  The final report of donor eligibility determination, including donor screening 
and testing results and interpretation of the results (see section IV.F. Final 
Donor Eligibility Determination); and  
10. Any additional information impacting the donor eligibility determination, 
including any additional species or product specific considerations, or 
deviations from procedures.     
C.  Relevant Disease Agents 
1.  Definition 
In this guidance, the term relevant disease agent means any transmissible agent, for 
which appropriate screening and/or testing measures exist, meeting any of the 
following conditions: 
 
  A disease agent that is potentially transmissible to the recipient of the ACTP, to 
other animals in contact with the recipient of the ACTP, or to people who may 
handle or come in contact with the ACTP, and: 
  The disease agent has a sufficient incidence or prevalence to support a risk 
of its presence in the donor population; or  
  The disease agent may have been released accidentally or intentionally in 
a manner that could place potential donors at risk of infection. 
  A disease agent that could be fatal or life-threatening, could result in permanent 
impairment of a body function or permanent damage to body structure, or could 
necessitate medical or surgical intervention.  
  A disease agent that is reportable to the United States Department of Agriculture, 
World Organization for Animal Health (OIE), or local government in the 
appropriate jurisdiction. 
  A disease agent that may affect the safety of edible tissues (for human or animal 
consumption) derived from food-producing animals treated with the ACTP. 
2.  List of relevant disease agents 
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As part of the donor selection criteria, you should develop a comprehensive list of 
relevant disease agents under consideration for your ACTP.  This is the list of agents 
to consider when determining which screening and testing procedures are appropriate.  
All factors described in the section above (see section IV.C.1. Definition) should be 
considered when determining if a disease agent is relevant.  
 
Lists of relevant disease agents for the dog, cat, and horse are included in Appendix 
A.  The lists are intended only as a guide for donor animals residing in the United 
States and are not comprehensive.  Additional disease agents may need to be 
considered for most ACTPs based on the donor species, donor selection criteria, 
availability of information on the donor population, tissue source and other 
characteristics of the ACTP, the manufacturing process, the intended recipient 
population, and indication.  For example, additional relevant disease agents may exist 
for donors with a travel history to, or residing in, regions endemic for specific disease 
agents not included on the list in Appendix A (e.g., travel or residence outside the 
United States).   
 
Sponsors of all ACTPs are encouraged to submit their donor selection criteria, 
including a list of relevant disease agents for their ACTP, to CVM for review early in 
the development process.  Sponsors using donor species other than the dog, cat, or 
horse, and sponsors developing ACTPs for use in food-producing animals, are 
encouraged to contact CVM to discuss relevant disease agents prior to submitting 
their donor selection criteria. 
 
D.  Donor Screening 
Donor screening should evaluate the donors general health and risk of exposure to 
relevant disease agents.  Donor screening should include both historical and clinical 
assessments of the donor to help prevent the introduction, transmission, or spread of 
diseases and to help ensure ACTP quality.  
 
1.  Donor screening information and evaluations 
Donor screening should include assessment of historical information and clinical 
evaluations.  At a minimum, you should have procedures for, and documentation of, 
the following information for each animal donor: 
  Historical Information 
  Description of the donor (e.g., this may include the source of the 
animal, identification, signalment, and ownership history); 
  Detailed medical history; 
  Detailed travel history; 
  Detailed vaccination history; 
6  Contains Nonbinding Recommendations 
  Detailed description of environmental and social history (e.g., this may 
include a description of  housing, management, exposure to other 
animals, movement of new animals onto the premises, exposure to 
wildlife, food and food source); and 
  Requirements for eligibility based on historical information. 
 
  Clinical Evaluations 
  Physical examinations, including an assessment of each body system 
and temperature, pulse, and respiration; 
  Clinical pathology;  
  Daily health observations;  
  Species-specific appropriate general health screening tests (e.g., fecal 
exam, heartworm test); 
  Procedures to reduce the risk of exposure to disease agents during the 
peridonation period (e.g., quarantine, restrictions on travel, restrictions 
on introduction of new animals); and 
  Requirements for eligibility based on screening evaluations and 
procedures 
2.  Donor screening considerations 
 
You should establish a peridonation period.  The peridonation period is the time 
during which a potential animal donor is observed for signs of clinical disease.  The 
peridonation period should include a time period both before and after donation 
sufficient to assess the donor for signs of recent disease or incubating disease agents.  
The duration of the peridonation period is based on the incubation period of relevant 
disease agents, as well as the product-specific historical and screening requirements 
for donors.  For example, the peridonation period for a donor from a pathogen-free, 
closed colony of dogs may be shorter than that for a client-owned pet dog.   
 
Procedures to reduce the risk of exposure to relevant disease agents (e.g., restrictions 
on travel, exposure to new animals, and exposure to wildlife) and to evaluate the 
general health of animal donors should occur throughout the peridonation period.   
 
All animal donors should be evaluated by a veterinarian5 and determined to be 
clinically healthy throughout the peridonation period such that the donor has no 
condition or characteristic that could impact the quality of the ACTP.  In general, a 
healthy animal donor has a state of wellbeing such that the animal has normal body 
function, productivity, and behavior, and absence of disease, and the environmental, 
behavioral, and nutritional needs of the animal are met.  An animal may be 
determined to be healthy in the presence of minor localized injuries or lesions (minor 
 
5 Veterinarians should hold a license or equivalent credentials as required by the locale in which they practice 
veterinary medicine. 
7  Contains Nonbinding Recommendations 
contusions, lacerations, burns, etc.) that are not associated with body temperature 
elevation or pain and distress.  The health of an animal donor should be based on 
evaluations, including, but not limited to, physical exams, clinical pathology, and 
species-specific appropriate tests.  At a minimum, these evaluations and tests should 
be performed at the beginning and end of the peridonation period, as well as at the 
time of donation.  Multiple veterinarians may perform these evaluations.  However, 
there should be a single individual responsible for making the donor eligibility 
determination (see Section IV.F.).    
 
In general, eligible animal donors should be required to survive the peridonation 
period.  If a potential animal donor dies or is euthanized prior to the end of the 
peridonation period for reasons that do not increase the risk of exposure to relevant 
disease agents (such as trauma), a complete and thorough necropsy should be 
performed, cause of death should be determined, the health of other animals on the 
premises should be assessed, and the donor animal should be tested for all possible 
relevant disease agents (those listed in Appendix A, as well as any other agents 
specific to the donor animals environment and history).  If the donation is intended 
to take place after the animal is deceased (for example, the donor is a healthy food-
producing animal and the donated sample will be recovered at slaughter, or the donor 
is a research animal where donation will occur after euthanasia), procedures to collect 
all relevant postmortem health information at the slaughter or research facility should 
be reviewed by CVM and in place prior to the time of donation. 
 
Historical information (medical, travel, vaccination, production, and environment) 
should be obtained and documented for a period long enough to assure absence of 
exposure to relevant disease agents resulting in chronic illness or latent infections.  In 
cases where sufficient historical information is not available, donor screening and 
testing evaluations should be designed to ensure absence of chronic and/or latent 
relevant disease agents. 
 
We recommend developing robust donor screening criteria, as there may be 
limitations associated with testing for certain relevant disease agents.  For example, 
some donor tests may be validated for use as a diagnostic test but not as a screening 
test in a healthy animal.  In this situation, the diagnostic test alone may not be 
sufficient to determine the donor is free from risk factors for, or clinical evidence of 
infection with the relevant disease agent.  However, in some circumstances, you may 
use robust screening criteria in combination with the diagnostic test to help support 
donor eligibility. 
 
E.  Donor Testing 
1.  Determining When to Test for a Disease Agent 
 
The presence of an agent on the list of relevant disease agents in Appendix A does not 
mean that a test for that agent must be carried out.  However, if not performing a test 
for a relevant disease agent listed in Appendix A, you should provide justification 
based on a risk assessment.  
8  Contains Nonbinding Recommendations 
 
In general, donors or the donated cells/tissues or product should be tested for all 
relevant disease agents for which screening information cannot rule out exposure to, 
or presence of, the relevant disease agent.  If not performing testing for a relevant 
disease agent, your donor eligibility determination process should specifically state 
which screening criteria justify the absence of that agent. 
 
The following are examples of justification for not testing for a relevant disease 
agent: 
  Disease/agent does not occur in the donors geographic location and the donor 
and donated material could not have been contaminated by this agent after 
donation.  Conclusive supporting official documented evidence should be 
provided (e.g., current OIE status). 
  Disease/agent does not occur in the colony/herd of origin (i.e., specific 
pathogen-free status).  Supporting documentary evidence should be provided 
for monitoring with serological and/or agent detection methods, accompanied 
by strict biosecurity measures.  
  Material cannot be contaminated with this agent (e.g., agent does not cross the 
placenta or agent is localized to a tissue not included in the donation).  Strong 
justification should be provided, such as evidence generated from the specific 
disease agent in the donor species (i.e., literature from similar disease agents 
or other species is generally insufficient).  For example, it is possible to prove 
that an agent regularly crosses the placenta, but it is more difficult to prove 
that an agent may never cross the placenta.  In this example, data evaluating 
the inability of the specific disease agent to cross the placenta in the donor 
species could be provided as justification.  
  The agent cannot survive the manufacturing process (e.g., the agent is 
inactivated using a validated method or is removed by the production 
process).   
  The agent will be identified by sterility testing as conducted per United States 
Pharmacopeia (USP) Chapter <71> Sterility Tests6 or equivalent test (e.g., the 
agent is an aerobe, anaerobe, or fungi). 
 
2.  Test Methods 
 
All test methods should be validated.  The parameters to be validated in each case 
should be chosen in agreement with the purpose of the assay.  You should refer to the 
appropriate USP chapter for additional information on test method validation.  We 
recommend submitting your test method validation early in the development process. 
 
You should utilize the most accurate and sensitive test method available for each 
agent.  Testing should be performed on the donor, donated cells/tissues or product, 
 
6 http://ftp.uspbpep.com/v29240/usp29nf24s0_c71.html 
9  Contains Nonbinding Recommendations 
whichever is most likely to identify the disease agent.  The specimen for testing 
should be collected, handled, and shipped according to standards set by the laboratory 
performing the test. 
 
For the detection of viruses, appropriate methods for virus isolation and identification 
should be used (cell cultures, embryonated eggs, animal inoculation) and criteria 
established (e.g., cytopathic effect, hemadsorption, immunostaining, etc.).  The 
sensitivity of the test for specified agents should be known, not only for laboratory 
adapted strains, but also for field (wild) strains.  Antigen and genome detection 
methods (e.g., PCR) can also be used.  The specificity of the test should be known 
(e.g., group or type specific). 
 
Sterility testing should be performed on all ACTPs.  Specific bacterial testing should 
be performed for bacteria that are not detectable by the sterility test, such as 
mycobacteria, mycoplasmas, and obligatory intracellular bacteria. 
 
Detection of an agent may also be based on detection of corresponding antibodies 
using appropriate serological methods.  
 
When choosing a contract laboratory to conduct relevant disease agent testing, we 
recommend that you consider the quality of the practices and procedures used by the 
laboratory (e.g., accreditations, availability of SOPs, review validation reports, etc.).  
Test methods should be validated and submitted to CVM for review.  
 
3.  Donor testing information  
 
Donor testing information should include, at a minimum, procedures for and 
documentation of: 
  Tests performed, including justification for the choice of test; 
  Sample to be tested; 
  Date/timing of sample collection; 
  Sample handling; 
  Laboratory performing the test; 
  Criteria for interpreting test results; 
  Test method validation; 
  Documentation of results; and 
  Requirements for eligibility based on testing. 
 
Donors should be considered eligible only if they have negative or nonreactive test 
results.  The donor selection criteria submitted to CVM should clearly define negative 
or nonreactive test results for each test and provide justification for the acceptability 
of those results where applicable.  The testing laboratories may provide the 
10  Contains Nonbinding Recommendations 
acceptable limits or cut off values for their tests.  You should further describe how 
you will interpret the results.  Interpretation of test results should be based on your 
specific donor selection criteria and product characteristics.  For example, serologic 
tests results should be interpreted based on donor and donor population 
characteristics, such as vaccination status.  Test method validation may be submitted 
with the donor selection criteria or with the final donor eligibility determination 
report. 
 
All results from testing of the donor and donated cells/tissues or product should be 
available prior to making the final donor eligibility determination. 
 
F.  Final Donor Eligibility Determination 
The final donor eligibility determination should be made by a responsible person who has 
appropriate training, qualifications, and authorization.  This person should review all 
records related to the donors eligibility status7 and determine and document the 
eligibility of the donor.  
 
A donor should be considered eligible if: 
  Donor screening and testing are conducted in a manner consistent with CGMP, 
and donor screening and testing addresses the considerations described in this 
guidance;  
  Donor screening indicates that the donor is healthy and free from risk factors for, 
and clinical evidence of, infection due to relevant disease agents and diseases; and 
  The results of donor and donated cells/tissues and product testing for relevant 
disease agents are negative or nonreactive. 
 
A final report should be created for each donor eligibility determination.  The final report 
should include: 
  Requirements for donor eligibility (donor selection criteria); 
  Documentation of donor screening and testing results; 
  Interpretation of donor screening and testing results;  
  A final statement of the eligibility (or lack of eligibility) of the donor;  
  Deviations from the donor selection criteria process; and   
  Qualifications of the person responsible for making the donor eligibility 
determination.   
 
 
7 In addition to donor screening and testing procedures and results, these records may include reports regarding 
disease outbreaks, additional donor medical records, and any other information necessary to determine that the 
donor is healthy and free from risk factors for, and clinical evidence of, relevant disease agents and diseases, and 
that donor test results for relevant disease agents are negative. 
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The final report and all raw data and documentation supporting the determination of 
donor eligibility, including validation of test methods, should be submitted to CVM in 
support of approval of the ACTP containing donated cells/tissue from each individual 
donation event.  
 
V.  PROCEDURES 
Any sponsors, firms, individuals, and establishments involved in determining donor eligibility 
should establish and maintain procedures for all steps they perform in testing, screening, 
determining donor eligibility, and complying with all other applicable CGMP.  That is, 
procedures should be defined, documented (in writing or electronically), and implemented; then 
followed, reviewed, and revised as needed on an ongoing basis.  All procedures should be 
reviewed and approved by a qualified person before implementation.  
 
Procedures for any operations should be readily available to the personnel in the area where the 
operations are performed, or in a nearby area if such availability is impractical.  
 
Any departures from established procedures and the justifications for those departures should be 
recorded at the time of occurrence.  ACTPs recovered from a donor whose eligibility is 
determined under a departure from procedures should not be made available for release unless 
the person responsible for determining donor eligibility has determined that the departure does 
not increase the risk of disease transmission with use of the ACTP. 
 
See GFI #253, section VII. Procedures for additional recommendations related to procedures.  
 
VI.  DONOR TRACKING 
If you perform any step in the manufacture of an ACTP during which you handle the donor 
cells/tissues, or product, you should track each ACTP.  A system should be in place to track all 
ACTPs from the donor through final distribution.  The system should also be able to track a 
specific product back to the donor.   
 
Each donor should be assigned a distinct identification code.  Donor cells or tissues should be 
identified by the distinct identification code from the time of donation, throughout all steps of the 
manufacturing process, and through final distribution of the ACTP.  The distinct identification 
code should be affixed to the ACTP container for both investigational and approved ACTPs. 
 
See GFI #253, section XIX. Tracking for additional recommendations related to tracking. 
 
VII.  RECORDS 
See GFI #253, section XVIII. Records for additional recommendations related to records. 
 
A.  Record maintenance and retention 
The following records related to donor eligibility determinations should be maintained: 
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  The final donor eligibility determination report;  
  Results and interpretation of all testing for relevant disease agents; 
  Results and interpretation of all donor screening evaluations and procedures; 
  The name and address of the laboratory(ies) performing the tests; 
  The name of the responsible person who made the donor eligibility determination; 
  The date of the donor eligibility determination; and 
  All other records supporting the donor eligibility determination. 
 
All records should be attributable, legible, contemporaneous, original, and accurate.  
Information on the identity and relevant medical records of the donor should be in 
English or, if in another language, should be retained and translated to English and 
accompanied by a statement of authenticity by the translator that specifically identifies 
the translated document so that compliance with CGMP can be more easily determined 
by FDA. 
 
All records relating to donor eligibility determination should be maintained and available 
for authorized inspection by or upon request from FDA.  Records that can be readily 
retrieved from another location by electronic means are considered "retained."  All 
records pertaining to a particular ACTP should be retained for at least 10 years after the 
date of the ACTPs distribution, disposition, or expiration, whichever is latest.8 
 
B.  Records accompanying the ACTP 
Once the donor eligibility determination has been made, the following records should 
accompany the ACTP at all times: 
  A distinct identification code affixed to the ACTP container that relates the ACTP 
to the donor and to all records pertaining to the ACTP; 
  A statement that the donor has been determined to be eligible or ineligible.  
  For ineligible donors, the reason for ineligibility should be stated.  
  For ineligible donors, the ACTP should be clearly labeled as originating 
from an ineligible donor until and throughout destruction of the ACTP; 
  A summary of the records used to make the donor eligibility determination, 
including a listing and interpretation of results for all relevant disease agents 
where donor testing was performed; and  
  The name and address of the establishment that made the donor eligibility 
determination. 
 
8 The regulations in 21 CFR 211.180 require that records be kept for at least 1 year after expiration.  However, we 
recognize that expiration of ACTPs varies from hours to an indefinite period of time for some cryopreserved 
ACTPs.  Additionally, some forms of contamination or safety concerns may not be evident until years after the 
product is manufactured.  For these reasons, we recommend a record retention period of at least 10 years. 
13  Contains Nonbinding Recommendations 
 
VIII.  QUARANTINE OF ACTPS 
ACTPs should be kept in quarantine until completion of the donor eligibility determination.  
Quarantine means the storage or identification of an ACTP in a physically separate area clearly 
identified for such use, or through use of other procedures, such as automated designation in 
order to prevent improper release.  Quarantined ACTPs should be clearly identified as such, and 
easily distinguishable from ACTPs available for release.   
 
If you transport an ACTP before completion of the donor eligibility determination, you should 
keep it in quarantine during transport.  Quarantined ACTPs should be accompanied by records: 
  Identifying the donor by the distinct identification code affixed to the ACTP container; 
  Stating that the donor eligibility has not been completed; and 
  Stating that the product must not be implanted, transplanted, infused, or transferred until 
completion of the donor-eligibility determination. 
 
Quarantined ACTPs should not be distributed for clinical use (use in client-owned animals); 
however, quarantined ACTPs may be used for non-clinical laboratory studies (studies in non-
client-owned animals) provided appropriate precautions are taken to prevent spread of any 
potential relevant disease agents beyond the laboratory.  The immediate container (and all other 
labeling components) of quarantined ACTPs should be clearly labeled, NOT FOR 
DISTRIBUTION:  NOT EVALUATED FOR INFECTIOUS SUBSTANCES. 
 
IX.  ACTPS FROM INELIGIBLE DONORS 
ACTPs from donors that have been determined to be ineligible should be stored or identified in a 
physically separate area clearly identified for such use, or follow other procedures, such as 
automated designation, that are adequate to prevent improper release until destruction or other 
disposition of the ACTP occurs. 
 
ACTPs from ineligible donors should not be distributed for clinical use (use in client-owned 
animals); however, ACTPs from ineligible donors may be used for nonclinical laboratory studies 
(studies in non-client-owned animals) provided appropriate precautions are taken to prevent 
spread of any potentially relevant disease agents beyond the laboratory.  The immediate 
container (and all other labeling components) of ACTPs from ineligible donors should be clearly 
labeled, WARNING:  NOT FOR DISTRIBUTION:  RISK OF DISEASE TRANSMISSION.  
If the donor tested positive for a specific relevant disease agent, then all labeling components 
should contain the additional statement, WARNING: Positive test results for [name of agent or 
disease].  If the product is distributed for a non-clinical use, the label should state, For 
Nonclinical Use Only. 
   
14  Contains Nonbinding Recommendations 
APPENDIX A 
 
This appendix provides a sample list of relevant disease agents for dogs, horses, and cats residing 
in the United States.  These lists are intended to be a guide and are not comprehensive.  These 
lists focus on disease agents that may not be detected by sterility testing.  For many ACTPs, 
additional relevant disease agents may need to be considered.   
 
Dogs 
 
Adenovirus  
Bluetongue virus 
Corona Virus 
Distemper Virus 
Herpes Virus 
Influenza Virus 
Oral Papilloma Virus 
Parainfluenza Virus 
Parvovirus  
Rabies Virus 
Swine Herpes Virus 1 
 
Anaplasma spp  
Babesia spp  
Bartonella vinsonii 
Borellia spp 
Brucella canis 
Erhlichia spp   
Leishmania spp 
Leptospira spp 
Mycoplasma haemocanis 
Neorickettsia spp  
Neospora caninum 
Rickettsia rickettsii 
Trypanosoma cruzi 
Dirofilaria immitis 
 
Horses 
 
Equine Adenovirus 
Equine Encephalomyelitis Viruses  
Equine Herpes Virus (EHV-1, EHV-4) 
Equine Infectious Anemia Virus  
Equine Influenza Virus 
Equine Parvovirus 
Equine Rhinitis Virus A and B 
Equine Rotavirus 
15  Contains Nonbinding Recommendations 
Equine Viral Arteritis Virus  
Rabies Virus 
Vesicular Stomatitis Virus 
West Nile Virus 
 
Anaplasma phagocytophilia  
Babesia caballi  
Borellia spp 
Neorickettsia risticii  
Theileria equi  
 
Cats 
 
Feline Calicivirus 
Feline Coronavirus/Feline Infectious Peritonitis virus 
Feline Foamy virus 
Feline Herpes virus 
Feline Immunodeficiency Virus 
Feline Leukemia Virus 
Feline Panleukopenia 
Rabies Virus 
Swine Herpes Virus 1 
 
Bartonella spp  
Candidatus Mycoplasma haemominutum 
Chlamydophila felis 
Cytauxzoon felis 
Mycoplasma haemofelis  
Toxoplasma gondii 
 
 
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