Guidance for Industry 
 
 
Eligibility Determination for Donors of 
Human Cells, Tissues, and Cellular 
and Tissue-Based Products (HCT/Ps)  
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD  20852-
1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at 
http://www.fda.gov/cber/guidelines.htm. 
 
For questions on the content of this guidance, contact the Division of Human Tissues, Office of 
Cellular, Tissue and Gene Therapies at 301-827-2002. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
August 2007 
    Contains Nonbinding Recommendations 
 
Table of Contents 
 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................2 
A.  What is the scope of this guidance?...........................................................................2 
B.  Who should read this guidance?................................................................................2 
III.  THE DONOR-ELIGIBILITY DETERMINATION ( 1271.50).................................2 
A.  What is a donor-eligibility determination?...............................................................2 
B.  Who makes the donor-eligibility determination?....................................................3 
C.  What are relevant communicable disease agents or diseases (RCDADs)?........3 
D.  What communicable disease agents or diseases, not listed in  1271.3(r)(1), have 
been determined to be relevant?................................................................................5 
E.  How will FDA handle other emerging infectious diseases in regard to HCT/P 
donor eligibility?.........................................................................................................7 
F.  What procedures must I establish and maintain?...................................................7 
G.  What records must accompany the HCT/P after the donor-eligibility 
determination has been completed?..........................................................................8 
H.  What records must I retain, and for how long?.......................................................9 
I.  What do I do with the HTC/Ps before the donor-eligibility determination has 
been completed?........................................................................................................10 
J.  May I ship an HCT/P that is in quarantine?..........................................................10 
K.  How do I store HCT/Ps from a donor who has been determined to be ineligible?
.....................................................................................................................................10 
IV.  DONOR SCREENING ( 1271.75)...............................................................................11 
A.  For what diseases or conditions must I screen cell and tissue donors?................11 
B.  How do I screen a donor who is one month of age or younger?...........................11 
C.  What sources of information do I review?.............................................................11 
D.  When may I perform an abbreviated donor screening procedure?.....................14 
E.  What risk factors or conditions do I look for when screening a donor?.............14 
F.  What clinical evidence do I look for when screening a donor?............................21 
G.  What physical evidence do I look for?....................................................................24 
V.  DONOR TESTING:  GENERAL ( 1271.80)..............................................................25 
A.  What requirements apply to laboratories performing donor testing for relevant 
communicable disease agents or diseases?.............................................................25 
i  Contains Nonbinding Recommendations 
 
B.  What type of test must I use?...................................................................................26 
C.  How do I perform the test and interpret test results?...........................................26 
D.  If a donor is one month of age or younger, from whom must I collect a 
specimen?...................................................................................................................27 
E.  When do I collect a specimen for testing?..............................................................27 
F.  May I test a specimen from a donor who has undergone transfusion or infusion?
.....................................................................................................................................28 
G.  What are some useful definitions related to hemodilution?..................................31 
VI.  DONOR TESTING:  SPECIFIC REQUIREMENTS ( 1271.85).............................31 
A.  For what diseases must I test all donors of HCT/Ps, and what tests should I use?
.....................................................................................................................................31 
B.  For what additional diseases must I test donors of viable, leukocyte-rich cells or 
tissue and what tests should I use?..........................................................................34 
C.  How do I assess a donor of dura mater for TSE?..................................................36 
VII.  ADDITIONAL SCREENING AND TESTING REQUIREMENTS FOR DONORS 
OF REPRODUCTIVE CELLS AND TISSUES ( 1271.75, 1271.80, AND 1271.85)
...........................................................................................................................................36 
A.  Do I need to screen and test all donors of reproductive cells and tissue?............36 
B.  What additional screening must I do for donors of reproductive cells and tissue?
.....................................................................................................................................36 
C.  What additional testing must I perform on donors of reproductive cells and 
tissue?.........................................................................................................................36 
D.  What follow-up testing is required for anonymous semen donors?.....................37 
E.  Is follow-up testing required for directed donors of semen?................................38 
F.  Is a donor eligibility determination required for gestational carriers or surrogate 
carriers?.....................................................................................................................38 
G.  Is a donor eligibility determination required for donors of reproductive cells and 
tissues that are transferred to gestational or surrogate carriers?........................38 
VIII.  EXCEPTIONS FROM THE REQUIREMENTS FOR DETERMINING DONOR 
ELIGIBILITY AND SPECIAL CIRCUMSTANCES ( 1271.90, 1271.60(D), 
1271.65(B), AND 1271.65(C)).........................................................................................39 
A.  When is a donor eligibility determination not required?  ( 1271.90).................40 
B.  What special labeling is required for HCT/Ps that are excepted under the 
provision of  1271.90(a) from the donor eligibility determination ( 1271.90(b)(1 
through 6))?...............................................................................................................42 
C.  Can cells or tissue from a donor be used before the donor eligibility 
determination under 1271.50 (a) is completed?...................................................44 
ii  Contains Nonbinding Recommendations 
 
D.  Can cells or tissue from an ineligible donor ever be used for implantation, 
transplantation, infusion, or transfer? ( 1271.65(b))...........................................45 
E.  Are there any other uses for human cellular and tissue-based HCT/Ps from 
donors determined to be ineligible?........................................................................46 
IX.  IMPLEMENTATION....................................................................................................46 
X.  REFERENCES................................................................................................................46 
APPENDIX 1...............................................................................................................................58 
APPENDIX 2...............................................................................................................................60 
APPENDIX 3...............................................................................................................................61 
APPENDIX 4...............................................................................................................................62 
APPENDIX 5...............................................................................................................................63 
APPENDIX 6...............................................................................................................................64 
 
 
iii  Contains Nonbinding Recommendations 
 
Guidance for Industry 
 
Eligibility Determination for Donors of Human Cells, Tissues, and 
Cellular and Tissue- Based Products (HCT/Ps) 
 
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on this 
topic.  It does not create or confer any rights for or on any person and does not operate to bind 
FDA or the public.  You can use an alternative approach if the approach satisfies the 
requirements of the applicable statutes and regulations.  If you want to discuss an alternative 
approach, contact the appropriate FDA staff.  If you cannot identify the appropriate FDA staff, 
call the appropriate number listed on the title page of this guidance. 
 
 
I.  INTRODUCTION 
 
We, FDA, are issuing this guidance to assist you, establishments making donor eligibility 
determinations, with complying with the requirements in Title 21 Code of Federal Regulations, 
part 1271, subpart C (21 CFR part 1271, subpart C) (Ref. 1).  The regulations under 21 CFR part 
1271, subpart C set out requirements for determining donor-eligibility, including donor screening 
and testing, for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps).   
 
This guidance applies to cells and tissues procured on or after the effective date of the 
regulations contained in 21 CFR part 1271, subpart C (effective date May 25, 2005).  This 
guidance replaces the guidance of the same title, dated February 27, 2007.  This guidance does 
not replace the guidance concerning 21 CFR part 1270, entitled Guidance for Industry: 
Screening and Testing of Donors of Human Tissue Intended for Transplantation, (Ref. 2), 
which remains applicable to tissues recovered before May 25, 2005 and subject to 21 CFR part 
1270.  
 
We recognize that some HCT/Ps (e.g., hematopoietic stem cells), as well as Whole Blood and 
blood components, can be collected by venipuncture from living donors.  We encourage you to 
contact the Center for Biologics Evaluation and Research (CBER) should you have any 
questions as to the applicable regulatory framework for collection and further processing of such 
products.  
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the FDAs 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 FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
1 
  Contains Nonbinding Recommendations 
 
II.  BACKGROUND 
 
A.  What is the purpose of this guidance? 
 
This guidance will assist establishments (HCT/P establishments) in complying with the 
requirements under 21 CFR part 1271, subpart C, for donor-eligibility determinations 
based on donor screening and testing for relevant communicable disease agents and 
diseases.  These requirements apply to all donors of cells or tissue used in HCT/Ps, 
except as provided under  1271.90.   
 
This guidance finalizes the draft guidance, Guidance for Industry:  Eligibility 
Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based 
Products (HCT/Ps) dated May 2004, (Ref. 3).  This guidance also finalizes the draft 
guidance, Guidance for Industry:  Preventive Measures to Reduce the Possible Risk of 
Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease 
(vCJD) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), 
dated June 2002 (Ref. 4).    
 
B.  What is the scope of this guidance? 
 
This guidance is intended for: (1) Establishments responsible for performing any part of 
donor eligibility screening or testing, or for making donor-eligibility determinations; and 
(2) establishments that determine that an HCT/P meets release criteria and make the 
HCT/P available for distribution.     
   
Establishment, as defined under  1271.3(b), means a place of business under one 
management, at one general physical location, that engages in the manufacture of 
HCT/Ps.  This includes any individual, partnership, corporation, association, or other 
legal entity engaged in the manufacture of HCT/Ps, and includes facilities that engage in 
contract manufacturing.  An establishment may engage another establishment under a 
contract, agreement, or other arrangement for screening and testing donors and for 
determining whether donors are eligible.  Such allocations of responsibilities must 
comply with  1271.150(c)1. 
 
 
III.  THE DONOR-ELIGIBILITY DETERMINATION ( 1271.50) 
 
A.  What is a donor-eligibility determination? 
 
A donor-eligibility determination is a conclusion that a donor is either eligible or 
ineligible to donate cells or tissues to be used in an HCT/P, based on the results of donor 
screening ( 1271.75) and testing ( 1271.80 and 1271.85).  Except in certain situations 
                                                 
 
1 See Food and Drug Administration, Guidance for Industry: Compliance with 21 CFR Part 1271.150(c)(1)  
Manufacturing Arrangements, dated September  2006.   http://www.fda.gov/cber/guidelines.htm. 
2 
  Contains Nonbinding Recommendations 
 
specified under  1271.60(d), 1271.65(b), and 1271.90, an HCT/P must not be 
implanted, transplanted, infused, or transferred until the donor has been determined to be 
eligible ( 1271.45(c)).   
 
Under  1271.50(b), a donor is eligible only if: 
 
  Screening shows that the donor is free from risk factors for, and clinical evidence 
of, infection due to relevant communicable disease agents and diseases, and is 
free from communicable disease risks associated with xenotransplantation; and 
  Test results for relevant communicable disease agents are negative or nonreactive, 
except as provided in  1271.80(d)(1) for non-treponemal screening tests for 
syphilis. 
 
B.  Who makes the donor-eligibility determination? 
 
In accordance with  1271.50(a), a responsible person must determine and document 
the eligibility of a cell or tissue donor.  A responsible person is one who is authorized to 
perform designated functions for which he or she is trained and qualified ( 1271.3(t)).  A 
responsible person should have appropriate medical training and adequate knowledge of 
relevant Federal regulations and guidances.     
 
C.  What are relevant communicable disease agents or diseases (RCDADs)?   
 
There are two groups of relevant communicable disease agents and diseases.  The first 
group consists of those communicable diseases and disease agents specifically listed in  
1271.3(r)(1).  The second group consists of communicable diseases and disease agents 
described under  1271.3(r)(2), that are not specifically listed in  1271.3(r)(1).  These 
two groups are as follows: 
 
1.  Relevant communicable disease and disease agents specifically listed in  
1271.3(r)(1). 
 
a.  The following communicable diseases and disease agents are relevant for 
all types of HCT/Ps ( 1271.3(r)(1)(i)):  
 
  Human immunodeficiency virus (HIV), types 1 and 2;  
  Hepatitis B virus (HBV); 
  Hepatitis C virus (HCV); 
  Human transmissible spongiform encephalopathy (TSE); including 
Creutzfeldt-Jakob disease (CJD)2; and  
  Treponema pallidum (syphilis). 
 
                                                 
 
2 Variant Creutzfeldt-Jakob disease (vCJD) is not specifically listed in  1271.3(r)(1)(i), but is an example of human 
transmissible spongiform encephalopathy.  
3 
  Contains Nonbinding Recommendations 
 
b.  The following cell-associated communicable disease or disease agents are 
relevant for viable, leukocyte-rich cells and tissues, including reproductive 
cells or tissues if they are considered to be viable leukocyte rich (see section 
VI.B.2. of this document) ( 1271.3(r)(1)(ii)): 
 
  Human T-lymphotropic virus (HTLV), types I and II. 
 
c.  The following communicable disease agents or diseases of the 
genitourinary tract are relevant for reproductive cells or tissues ( 
1271.3(r)(1)(iii)):   
 
  Chlamydia trachomatis; and  
  Neisseria gonorrhea. 
 
2.  A communicable disease agent or disease meeting the criteria described in  
1271.3(r)(2), but not specifically listed in  1271.3(r)(1), is relevant if it is one: 
 
a.  For which there may be a risk of transmission by an HCT/P, either to the 
recipient of the HCT/P or to those people who may handle or otherwise come 
in contact with the HCT/P, such as medical personnel, because the disease 
agent or disease: 
 
i.  is potentially transmissible by an HCT/P; and  
ii.  either (1) has sufficient incidence and/or prevalence to affect the 
potential donor population ( 1271.3(r)(2)(i)(B)(1)), or (2) may have been 
released accidentally or intentionally in a manner that could place 
potential donors at risk of infection ( 1271.3(r)(2)(i)(B)(2));  
 
b.  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 to preclude permanent 
impairment of body function or permanent damage to a body structure ( 
1271.3(r)(2)(ii)); and 
 
c.  For which appropriate screening measures have been developed and/or an 
appropriate screening test for donor specimens has been licensed, approved, or 
cleared for such use by FDA and is available ( 1271.3(r)(2)(iii)). 
 
In summary, FDA considers:  (1) Risk of transmission, (2) severity of effect, and (3) 
availability of appropriate screening measures or tests, in accordance with  1271.3(r)(2), 
as factors in determining whether a communicable disease or disease agent, not listed 
under  1271.3(r)(1), is relevant.  The importance of these factors in determining 
relevance may be based on the clinical significance of the disease agent or disease.  For 
example, Ureaplasma urealyticum, although highly prevalent and transmissible, is not 
considered a relevant communicable disease agent because its pathogenicity to 
4 
  Contains Nonbinding Recommendations 
 
reproductive cell and tissue recipients has low clinical significance.  However, we require 
screening for TSEs and screening or testing for HIV-2, although less prevalent, because 
they pose extremely significant health risks.    
 
D.  What communicable disease agents or diseases, not listed in  1271.3(r)(1), have 
been determined to be relevant? 
 
We have determined the following communicable disease agents and diseases, not 
specifically listed under  1271.3(r)(1), to be relevant under  1271.3(r)(2).  This 
determination was based on the risk of transmission, severity of effect, and availability of 
appropriate screening measures or tests as described in section III.C. of this document.  A 
brief discussion of these factors is provided under each relevant disease and agent listed.  
Additional background information is provided in the appendix, as indicated. 
 
West Nile Virus (WNV)  
 
Risk of Transmission:  There is a risk of transmission of WNV by HCT/Ps.  This 
is supported by observations of WNV transmission via organ transplantation, and 
via blood and blood product transfusion.  Although it is not possible to predict the 
incidence or severity of future WNV epidemics, our experience with the 
transmission pattern of WNV and the rapid geographic spread of the disease 
epidemic suggests that all or most of the United States would be at risk for 
exposure to the illness each year.  WNV activity in birds and mosquitoes has been 
documented year-round in states with warm winter climates.  Human infection in 
these areas is a theoretical risk at all times of the year (Ref. 5).  (See Appendix 6). 
 
Severity of Effect:  WNV could be fatal or life-threatening, result in permanent 
impairment of a body function or permanent damage to a body structure, and/or 
necessitate medical or surgical intervention to preclude permanent impairment of 
a body function or permanent damage to a body structure. 
 
Availability of Appropriate Screening and/or Testing Measures:  Appropriate 
screening measures have been developed for WNV, such as the medical history 
interview and clinical evidence (see Refs. 5, 6, and 7 for further information 
regarding the background and rationale for WNV deferral). (Screening measures 
for WNV are discussed in sections IV.E. and IV.F. of this document.)  
A donor screening test for WNV, using NAT technology, has been licensed for 
use in living and cadaveric HCT/P donors.  IND studies are also ongoing for the 
development of other NAT screening tests for WNV (see section VI.A. and 
Appendix 6).   
 
Sepsis 
 
Risk of Transmission:  There is a risk of transmission by HCT/Ps of any agent that 
could cause sepsis.  The agents that cause sepsis include various bacterial, fungal, 
and viral agents.  These agents have sufficient incidence and/or prevalence to 
5 
  Contains Nonbinding Recommendations 
 
affect the potential HCT/P donor population and are potentially transmissible.  
For the purpose of this document, sepsis includes, but is not limited to, 
bacteremia, septicemia, sepsis syndrome, systemic infection, systemic 
inflammatory response syndrome (SIRS), or septic shock (see Appendix 6). 
 
Severity of Effect:  Sepsis could be fatal or life-threatening, result in permanent 
impairment of a body function or permanent damage to a body structure, and/or 
necessitate medical or surgical intervention to preclude permanent impairment of 
a body function or permanent damage to a body structure.  Mortality from sepsis 
is substantial, as sepsis is now among the top ten leading causes of death in the 
United States (see Appendix 6). 
 
Availability of Appropriate Screening and/or Testing Measures:  Appropriate 
screening measures have been developed for detection of sepsis, such as the 
medical history interview, and clinical and physical evidence.  (Screening 
measures for sepsis are discussed in sections IV.E., IV.F. and IV.G. of this 
document.) 
 
Vaccinia  
 
Risk of Transmission:  There is a risk of transmission of vaccinia (the virus used 
in smallpox vaccine) by HCT/Ps.  Vaccinia has sufficient incidence and/or 
prevalence to affect the potential donor population, especially in light of current 
small pox vaccination programs.  Although there are no documented cases of 
transmission of vaccinia virus through implantation, transplantation, infusion, or 
transfer of HCT/Ps into a human recipient, two different investigators reported 
that vaccinia virus could sometimes be isolated from a patients blood 3 to10 days 
after vaccination (Ref. 8).  These studies did not use the less virulent New York 
City Board of Health (NYCBOH) strain of vaccinia virus that comprises currently 
available vaccines in the United States.  Other investigators using the NYCBOH 
strain of vaccinia virus were only able to detect virus in the blood of patients with 
disseminated infection, but not in patients who only had localized lesions (Refs. 9 
and 10).  These studies are of limited value, however, because of their small size.  
Studies are now underway to determine the presence and frequency of vaccinia 
virus in the blood after vaccination (see Appendix 6). 
 
Severity of Effect:  Vaccinia virus could be fatal or life-threatening, result in 
permanent impairment of a body function or permanent damage to a body 
structure, and/or necessitate medical or surgical intervention to preclude 
permanent impairment of a body function or permanent damage to a body 
structure.  Historically, for every million people vaccinated in the past, up to 52 
people have had a life-threatening reaction to smallpox vaccine and up to two 
people per million vaccinated have died (Refs. 10 and 11). 
 
6 
  Contains Nonbinding Recommendations 
 
The potential consequences of vaccinia infection include severe complications 
(see Appendix 4).  These consequences are more likely to occur in HCT/P 
recipients who are immunocompromised or who have burns or other serious skin 
conditions.  Vaccinia virus infection rarely causes severe complications such as 
encephalitis and severe generalized vaccinia in otherwise healthy people.  Also, 
the route of infection could influence the severity of the disease, so that it is 
possible that vaccinia infection transmitted via HCT/Ps could result in different or 
more severe infections than when acquired percutaneously (Ref. 12).       
 
Availability of Appropriate Screening and/or Testing Measures:  There are 
appropriate screening measures, such as the medical history interview, and 
clinical and physical evidence (see Ref. 12 for further information regarding the 
background and rationale for vaccinia deferral).   (Screening measures for 
vaccinia are discussed in sections IV.E., IV.F. and IV.G. of this document.) 
 
E.  How will FDA handle other emerging infectious diseases in regard to HCT/P 
donor eligibility? 
 
We intend to notify you through a guidance, if we determine that an infectious disease 
meets the definition of a relevant communicable disease under  1271.3(r)(2).  The 
guidance would include our comments or recommendations for donor screening and 
testing.  We also intend to notify you through a guidance, if we conclude that a disease 
identified as relevant under  1271.3(r)(2), no longer meets the criteria as a relevant 
disease for purposes of the donor eligibility regulations.  In suitable situations, we will 
hold public meetings or consult with advisory committees to help us identify 
communicable disease agents or diseases for which donor screening and testing must be 
performed under  1271.75, 1271.80, and 1271.85. 
 
F.  What procedures must I establish and maintain?     
 
You must establish and maintain procedures for all steps that you perform in testing, 
screening, determining donor eligibility, and complying with all other requirements of 
part 1271, subpart C ( 1271.47(a)).  A responsible person must review and approve all 
procedures before their implementation ( 1271.47(b)).  These procedures must be 
readily available to personnel in the area where the procedures are performed, or if this is 
not practical, in a nearby area ( 1247(c)).   
 
Under  1271.47(d), at the time a departure occurs, you must record and justify that 
departure from a procedure relevant to preventing risks of communicable disease 
transmission.  Before distributing an HCT/P manufactured under a departure from a 
procedure, a responsible person must determine that the departure did not increase the 
risk of communicable disease transmission.   
 
We consider a departure to be an intended change from an established procedure, 
including a standard operating procedure (SOP), which occurs before the HCT/P is 
distributed, and is consistent with applicable regulations and standards.  For example, a 
7 
  Contains Nonbinding Recommendations 
 
departure might include the use of a different manufacturers reagents because the usual 
manufacturers reagents were not available at the recovery site.  In this example, although 
the use of the different manufacturers reagent might represent a change from the 
established procedures, the change might be consistent with applicable regulations, 
standards, or established specifications.  A departure is different from an HCT/P 
deviation, which under  1271.3(dd) is defined as an event that is inconsistent with 
applicable regulations, standards, or established specifications, or is unexpected or 
unforeseeable.   
 
You are authorized under 1271.47(e) to use appropriate standard procedures developed 
by another organization, provided that you have verified that the procedures are 
consistent with and at least as stringent as the requirements in part 1271.  For example, 
you may use a current donor medical history questionnaire developed by a professional 
organization, provided that you have reviewed the questionnaire and determined that it 
meets the requirements for donor screening.   
 
G. What records must accompany the HCT/P after the donor-eligibility 
determination has been completed? 
 
Under  1271.55(a) you must provide the following records with each HCT/P, after the 
donor-eligibility determination has been completed:   
 
  A distinct identification code (such as an alphanumeric code) affixed to the 
HCT/P container, that relates the HCT/P to the donor and to all records pertaining 
to the HCT/P and, except in the case of autologous donations, directed 
reproductive donations, or donations made by first-degree or second-degree blood 
relatives, does not include an individuals name, social security number, or 
medical record number; 
  A statement whether, based on the results of screening and testing, the donor is 
determined to be eligible or ineligible; and  
  A summary of the records used to make the donor-eligibility determination. 
 
Under 1271.55(b), the summary of records in  1271.55(a)(3) must include: 
 
  A statement that the communicable disease testing was performed by a laboratory 
or laboratories:  (1) certified to perform such testing on human specimens under 
the Clinical Laboratory Improvement Amendments of 1988 (42 U.S.C. 263a) and 
42 CFR part 493; or (2) meeting equivalent requirements, as determined by the 
Centers for Medicare and Medicaid Services (CMS);  
  A listing and interpretation of the results of all tests performed for relevant 
communicable disease agents or diseases, and, if applicable, for CMV 
( 1271.85(b)(2))3;  
                                                 
 
3 If a repeat anonymous semen donor has multiple tests for CMV and during this time he seroconverts (he initially 
tests CMV negative and subsequently tests CMV positive), then in the summary of records you should indicate the 
CMV positive result, or you may provide information about all CMV test results. 
8 
  Contains Nonbinding Recommendations 
 
  The name and address of the establishment that made the donor-eligibility 
determination; and 
  A statement noting the reason for the determination of ineligibility in the case of 
an HCT/P from a donor who is ineligible based on screening and released under  
1271.65(b).   
 
The records referenced in  1271.55 must accompany an HCT/P when it is placed into 
distribution (as defined in  1271.3(bb)), including distribution that occurs within the 
same facility (e.g., peripheral blood stem/progenitor cells are collected within a facilitys 
cell processing laboratory and are then sent to a patients floor in that same facility).  
Once the consignee receives the accompanying records with the HCT/P, it is not 
necessary that those records physically accompany the HCT/P into the operating room or 
at the bedside (except for any information that is affixed to the HCT/P container).  You 
should make accompanying records available for review by any medical personnel 
needing access to those records in order to provide patient care.  Electronic access to 
accompanying records within a facility would satisfy the regulatory requirements under  
1271.55(a), as long as they are in compliance with  1271.55(c)  deletion of personal 
information.   
 
Records that must accompany an HCT/P shipped under quarantine are discussed in 
section III.J. of this document. 
 
H. What records must I retain, and for how long? 
 
Under  1271.55(d)(1), you must retain records of results and interpretation of all testing 
for relevant communicable disease agents and screening for communicable diseases, the 
name and address of the testing laboratory, and the donor eligibility determination, 
including the name of the responsible person who made the donor eligibility 
determination, and the date of the determination.   
 
Under  1271.55(d)(2), all records must be accurate, indelible, and legible. 
 
Under  1271.55(d)(4), you must retain records pertaining to a particular HCT/P for at 
least 10 years after the date of its administration.  This includes records created by 
laboratories performing donor eligibility testing ( 1271.55(d)).  If the date of 
administration is not known, then you must retain records at least 10 years after the date 
of distribution, disposition, or expiration, whichever is latest ( 1271.55(d)(4)).  Testing 
laboratories that are not aware of the date of administration, distribution, disposition or 
expiration, should retain records for at least 10 years after the record was created (i.e., 
after the testing was performed).  
 
9 
  Contains Nonbinding Recommendations 
 
I.  What do I do with the HCT/Ps before the donor-eligibility determination has 
been completed? 
 
Before the completion of the donor-eligibility determination, you must keep an HCT/P in 
quarantine and clearly identify it as in quarantine ( 1271.60(a) and (b)).  The 
quarantined HCT/P must be easily distinguishable from HCT/Ps that are available for 
release and distribution ( 1271.60(b)). 
 
Quarantine means the storage or identification of an HCT/P, to prevent improper release, 
in a physically separate area clearly identified for such use, or through use of other 
procedures, such as automated designation ( 1271.3(q)).  An example of automated 
designation is the use of a validated computer system to maintain information on bar-
code-labeled HCT/Ps held in a freezer.  When you release the HCT/P, the computer 
system is activated to assure identification and retrieval of the specific HCT/P for the 
intended recipient.   
 
J.  May I ship an HCT/P that is in quarantine? 
 
Yes, you may ship an HCT/P before completion of the donor-eligibility determination ( 
1271.60(c)).  However, in accordance with  1271.60(c), the HCT/P must be kept in 
quarantine and must be accompanied by records that: 
 
  Identify the donor (e.g., by a distinct identification code affixed to the HCT/P 
container);  
  State that the donor-eligibility determination is not complete; and 
  State that the HCT/P must not be implanted, transplanted, infused, or transferred 
until the donor-eligibility determination is complete, except in cases of urgent 
medical need under  1271.60(d), and described in section VIII.C. of this 
document. 
 
K. How do I store HCT/Ps from a donor who has been determined to be ineligible? 
 
Under  1271.65(a), if a donor is determined to be ineligible you must store or identify 
the HCT/Ps from the ineligible donor in a physically separate area clearly identified for 
such use, or follow other procedures that are adequate to prevent improper release, until 
the HCT/Ps are destroyed or distributed for use in certain limited circumstances identified 
in  1271.65 (b) and (c), and described in section VIII.D. of this document.  Examples of 
ways in which you may comply with this requirement, include employing separate 
refrigerators or freezers, using separate shelves in a single refrigerator or freezer, and 
using an automated designation system.   
 
In accordance with  1271.47(a), you must describe in your standard operating 
procedures (SOPs) the method you choose to store or identify the HCT/Ps from the 
ineligible donor.   
 
 
10 
  Contains Nonbinding Recommendations 
 
IV.  DONOR SCREENING ( 1271.75) 
 
A.  For what diseases or conditions must I screen cell and tissue donors?  
 
Under  1271.75(a), you must screen a cell and tissue donor by reviewing relevant 
medical records for risk factors for, and clinical evidence of, relevant communicable 
disease agents and diseases; and communicable disease risks associated with 
xenotransplantation, unless an exception identified in  1271.90(a) applies.  For donors of 
viable, leukocyte-rich cells or tissue, you must also screen for HTLV ( 1275.75(b)).  
You must also screen donors of reproductive cells and tissue for the additional diseases 
identified as relevant to those HCT/Ps in  1271.75(c).  (See section III.C. of this 
document for discussion of relevant communicable disease agents and diseases.)  
 
B.  How do I screen a donor who is one month of age or younger?  
 
Under  1271.75, you must screen all donors, including infant donors one month of age 
or less, except as provided under  1271.90.  Since a donor who is one month of age or 
younger cannot participate in the donor medical history interview, you must interview 
another individual able to provide the information sought in the interview ( 
1271.3(n)(2)).  
 
You should also screen the birth mother when an infant is one month of age or less.  
Donor screening of the birth mother should involve a donor medical history interview 
and review of available medical records;  the physical examination or physical 
assessment of the birth mother is recommended when practical.   
 
C.  What sources of information do I review? 
 
When you screen a potential cell or tissue donor, you must review relevant medical 
records for risk factors for, and clinical evidence of, the relevant communicable diseases 
listed in  1271.75(a)(1).  Risk factors are described in section IV.E., clinical evidence in 
section IV.F., and physical evidence in section IV.G.   
 
Relevant medical records, as defined under  1271.3(s), means a collection of documents 
that includes:  (1) a current donor medical history interview; (2) a current report of the 
physical assessment of a cadaveric donor or the physical examination of a living donor; 
and (3) other available records listed in  1271.3(s)(1) through (4).  We describe these 
three elements as follows: 
 
1.  The donor medical history interview ( 1271.3(n)) is a documented dialogue 
concerning the donor's medical history and relevant social behavior:   
 
11 
  Contains Nonbinding Recommendations 
 
a.  With a living donor; or 
 
b.  If the donor is not living or is unable to participate in the interview, then 
with one or more individuals who can provide the information sought.  These 
individuals might be:  
 
  The donors next of kin; 
  The nearest available relative;  
  A member of the donors household; 
  An individual with an affinity relationship with the donor (e.g., 
caretaker, friend, partner); or 
  The donors primary treating physician.  
 
In accordance with  1271.47, you must establish and maintain standard operating 
procedures to assure that receipt and review of relevant medical records are properly 
conducted.  In addition, for medical records created for the purpose of assisting in 
determining donor eligibility, such as records of the donor medical history interview 
and the report of a physical assessment of a cadaveric donor, you must establish and 
maintain SOPs to assure that such records are current, complete, and reliable.   
 
The medical history interview may take place in person or by telephone.   
 
Since a donor medical history interview is a documented dialog ( 1271.3(n)), if a 
donor medical history questionnaire is self-administered, the interviewer should 
review and verify the answers with the individual who has filled out the questionnaire 
form. 
 
2.  The purpose of the physical assessment of a cadaveric donor or the physical 
examination of a living donor is to assess for physical signs of a relevant 
communicable disease and for signs suggestive of any risk factor for such a 
disease.  For a cadaveric donor, the physical assessment means a limited autopsy, 
or a recent antemortem or postmortem physical examination ( 1271.3(o)).  For 
living donors, you may examine only those parts of the body that are necessary to 
evaluate for RCDADs based upon relevant donor history that has been obtained 
during the interview and review of available records.  You may rely on records of 
a recent report of a physical examination by other health care professionals (see 
section IV.G. of this document for discussion about physical evidence).  Because 
this is a step in determining donor eligibility, you must establish and maintain 
standard operating procedures (SOPs) for the conduct of the physical assessment 
or physical examination ( 1271.47).     
 
3.  If they are available, the following other records also meet the definition of 
relevant medical records ( 1271.3(s)).    
 
  Laboratory test results (other than the results of testing required for the donor-
eligibility determination); 
12 
  Contains Nonbinding Recommendations 
 
  Medical records;  
  Coroner and autopsy reports; and 
  Records or other information received from any source pertaining to risk 
factors for relevant communicable disease (e.g., social behavior, clinical signs 
and symptoms of relevant communicable disease, and treatments related to 
medical conditions suggestive of risk for relevant communicable disease).  
Examples of these records include:  medical examiner reports, police records, 
and information from other tissue or medical establishments, if applicable.   
 
You should make inquiries into these records and other information when the 
circumstances indicate that follow-up information might be relevant for screening a 
potential cell or tissue donor.   For example, when reviewing the relevant medical 
records, including the medical/social history interview, the tissue bank might find 
information to suggest that the donor might have been incarcerated, pursued by the 
police, or been under police investigation, or that the cause of death resulted in a 
police report (e.g., fatal gunshot wound).  If that is the case, the tissue bank should 
make inquiries to obtain all relevant information regarding the eligibility of the donor, 
which is available from and disclosable by the police department. 
 
We define available to mean that a record or information exists, or is pending, and 
can be obtained through due diligence, within a reasonable amount of time.  A 
reasonable amount of time is a period of time that would allow for the collection of 
important information without compromising the utility of the tissue.  Examples of 
these terms are as follows: 
 
Example 1:  A living donor brings his medical records with him to the 
screening site.  These records are available, and you would review them. 
 
Example 2:  A cadaveric donor dies as a result of an event that leads to the 
creation of a police report.  If the police report was disclosable to you within a 
reasonable period of time, you would review it.   
 
Example 3:  You know that an autopsy report will be prepared on a cadaveric 
donor, but the report will not be complete for several weeks.  If waiting several 
weeks to review the autopsy report would compromise the utility of the tissue, 
perhaps because your HCT/P (e.g., cornea) needs to be released within a limited 
timeframe, then the report could not be obtained in a reasonable time period.  
Under these circumstances, it might not be necessary to wait to review the final 
report of autopsy results before distribution of the HCT/P.  If this is the case, you 
should use the available information when considering the donors eligibility, 
including the presumed cause of death and other relevant preliminary autopsy 
findings and all other information obtained about the donor.  Also, you should 
review the final autopsy report when it becomes available.  If any new 
information in the final report indicates that the donor is ineligible, you should 
consider notifying the consignees of  the distributed HCT/Ps and submit to FDA 
an HCT/P deviation report within 45 days, if applicable. 
13 
  Contains Nonbinding Recommendations 
 
 
D.  When may I perform an abbreviated donor screening procedure? 
 
Section 1271.75(e) states, If you have performed a complete donor screening procedure 
on a living donor within the previous 6 months, you may use an abbreviated donor 
screening procedure on repeat donations. The abbreviated procedure must determine and 
document any changes in the donors medical history since the previous donation that 
would make the donor ineligible, including relevant social behavior.  
 
If you perform an abbreviated screening: 
 
  You do not need to conduct a new physical examination or a new review of 
relevant medical records. 
  You should remind the donor about behaviors that could put him/her at risk of a 
relevant communicable disease.  If any new behavioral risk has been identified in 
the interval since the last donation, you should also address that new behavioral 
risk. 
  We do not require that this information be presented in any specific way.  
Possible methods include the use of a pamphlet or a wall chart, or other effective 
means of communication.   
  You should then ask the donor if there have been any changes in donor history or 
risk factors since the previous donation. 
 
If you wish to perform an abbreviated donor screening procedure, you must have 
conducted a complete donor screening procedure on the living donor (including donor 
history questionnaire, physical examination, and review of any new medical records, if 
applicable) within 6 months prior to the abbreviated procedure ( 1271.75(e)). 
 
E.  What risk factors or conditions do I look for when screening a donor? 
 
For all donors, you must review the relevant medical records and ask questions about the 
donors medical history and relevant social behavior, including risk factors for relevant 
communicable disease agents and diseases, and communicable disease risks associated 
with xenotransplantation ( 1271.75(a)).  
 
Following is a list of conditions and behaviors that increase the donors relevant 
communicable disease risk.  Except as noted in this section, and in accordance with  
1271.75(d), you should determine to be ineligible any potential donor who exhibits one 
or more of the following conditions or behaviors.   
 
1.  Men who have had sex with another man in the preceding 5 years (Refs. 17 
through 46) (risk factor for HIV and Hepatitis B).   
 
14 
  Contains Nonbinding Recommendations 
 
2.  Persons who have injected drugs for a non-medical reason in the preceding 5 
years, including intravenous, intramuscular, or subcutaneous injections (Refs. 18, 
21, 22, 25, 27, 29, 33, 34, 36, 38, 42, and 45 through 59) (risk factor HIV, 
Hepatitis B and Hepatitis C). 
 
3.  Persons with hemophilia or other related clotting disorders who have received 
human-derived clotting factor concentrates in the preceding 5 years (Refs. 18 and 
60) (risk factor for HIV, Hepatitis B and Hepatitis C).  A donor who received 
clotting factors once to treat an acute bleeding event more than 12 months ago 
may be eligible to donate. 
 
4.  Persons who have engaged in sex in exchange for money or drugs in the 
preceding 5 years (Refs. 18, 21, 22, 24, 25, 27, 29, 33, 34, 38, 40, 44, 45, 46, 61, 
62, and 63) (risk factor for HIV, Hepatitis B and Hepatitis C). 
 
5.  Persons who have had sex in the preceding 12 months with any person 
described in criteria 1 through 4 of this section or with any person who has HIV 
infection, including a positive or reactive test for HIV virus (Refs. 17 and 18), 
hepatitis B infection (Ref. 64), or clinically active (symptomatic) hepatitis C 
infection (Refs. 65 and 66).   
 
6.  Persons who have been exposed in the preceding 12 months to known or 
suspected HIV, HBV, and/or HCV-infected blood through percutaneous 
inoculation (e.g., needle stick) or through contact with an open wound, non-intact 
skin, or mucous membrane (Refs. 18 and 64).     
 
7.  Children born to mothers with or at risk for HIV infection: 
 
  If 18 months of age or younger, or 
  If breast-fed within the preceding 12 months. 
 
Note:  We do not recommend deferral of a donor who is a child born to a mother 
with or at risk for HIV infection if the child is over 18 months of age and has not 
been breast-fed within the preceding 12 months, provided that the childs HIV 
antibody tests, physical examination, and medical records do not indicate 
evidence of HIV infection (Ref. 18). 
 
8.  Persons who have been in juvenile detention, lock up, jail or prison for more 
than 72 consecutive hours in the preceding 12 months (Refs. 29, 67, and 68) (risk 
factor for HIV, Hepatitis B and Hepatitis C). 
 
9.  Persons who have lived with (resided in the same dwelling) another person 
who has hepatitis B or clinically active (symptomatic) hepatitis C infection in the 
preceding 12 months (Ref. 69).   
 
15 
  Contains Nonbinding Recommendations 
 
10. Persons who have undergone tattooing, ear piercing or body piercing in the 
preceding 12 months, in which sterile procedures were not used, e.g., 
contaminated instruments and/or ink were used, or shared instruments that had not 
been sterilized between uses were used (Ref. 69).  
 
11. Persons who have had a past diagnosis of clinical, symptomatic viral hepatitis 
after their 11th birthday (Refs. 70 and 71), unless evidence from the time of 
illness documents that the hepatitis was identified as being caused by hepatitis A 
virus, Epstein-Barr Virus (EBV), or cytomegalovirus (CMV).  
 
12. Persons who are deceased and have a documented medical diagnosis of sepsis 
or have documented clinical evidence consistent with a diagnosis of sepsis that is 
not explained by other clinical conditions at the time of death.  For example, if a 
statement such as rule-out sepsis is noted in the medical records, and 
subsequent notations indicate a diagnosis other than sepsis, a potential donor 
might still be eligible.   
 
13. Persons who have had smallpox vaccination (vaccinia virus) in the preceding 
8 weeks (Ref. 12) should be evaluated as follows:  
 
a.  For persons who had no vaccinia complications (see Appendix 4 for 
definition of vaccinia complication):  
   
  You should defer the donor until after the vaccination scab has 
separated spontaneously, or for 21 days post-vaccination, whichever is the 
later date, and until the physical examination or physical assessment 
includes a confirmation that there is no scab at the vaccination site.  
  In cases where a scab was removed before separating spontaneously, 
you should defer the donor for two months after vaccination.     
  
Note:  We do not recommend deferral of a cadaveric donor who was 
vaccinated at least 21 days ago and who has no visible scab, if you are unable 
to obtain a history of how the scab separated. 
 
b.  For persons who have experienced vaccinia complications (see Appendix 
4), you should defer the donor until 14 days after all vaccinia complications 
have completely resolved.   
 
Note:  We do not recommend deferral of a cadaveric donor who previously 
had vaccinia complications but who currently has no visible signs of vaccinia 
complications, if you are unable to obtain a history of the exact date of 
resolution of the vaccinia complications.   
 
16 
  Contains Nonbinding Recommendations 
 
14. Persons who acquired a clinically recognizable vaccinia virus infection by 
contact with someone who received the smallpox vaccine (i.e., touching the 
vaccination area or the scab, including the covering bandages, or touching 
clothing, towels, or bedding that might have come into contact with an 
unbandaged vaccination area or scab) (Ref. 12). 
 
  For living donors who developed skin lesions as a result of contact with 
someone who received the smallpox vaccine, you should question the 
donor regarding the loss of the scab, and you should examine the skin.  
For cadaveric donors, you should examine the skin.   
  If no scab is present, we do not recommend deferral of: 
o  a cadaveric donor; 
o  a living donor if the scab spontaneously separated; or  
o  after three months from the date of vaccination of the vaccine 
recipient, a living donor whose scab was otherwise removed. 
  If a scab is present, you should consider: 
o  a cadaveric donor to be ineligible; or 
o  a living donor to be deferred until the scab spontaneously 
separates. 
 
You should defer persons who developed other complications of vaccinia 
infection acquired through contact with a vaccine recipient until 14 days after all 
vaccinia complications have completely resolved. 
 
Note:   We do not recommend deferral of a cadaveric donor who previously had 
complications of vaccinia acquired through contact with a vaccine 
recipient, but has no visible signs of vaccine complications, if the date of 
resolution of the vaccinia complications is unknown.  
 
We do not recommend deferral of contacts who never developed skin 
lesions or other complications of vaccinia infection.   
 
15. Persons who have had a medical diagnosis or suspicion of WNV infection 
(based on symptoms and/or laboratory results, or confirmed WNV viremia) you 
should defer for 120 days following diagnosis or onset of illness, whichever is 
later (Refs. 5, 6, and 7). 
 
16. Persons who have tested positive or reactive for WNV infection using an 
FDA-licensed or investigational WNV NAT donor screening test in the preceding 
120 days (Refs. 5 and 7). 
 
17. Persons who have been treated for or had syphilis within the preceding 12 
months.  We do not recommend deferral of donors if evidence is presented that 
the treatment occurred more than 12 months ago and was successful.  
 
17 
  Contains Nonbinding Recommendations 
 
18. Reproductive HCT/P donors who have been treated for or had Chlamydia 
trachomatis or Neisseria gonorrhea infection in the preceding 12 months.  We do 
not recommend deferral of persons who have been treated for or had Chlamydia 
trachomatis or Neisseria gonorrhea infection if evidence is presented that the 
treatment occurred more than 12 months ago and was successful.   
 
Example:  A potential donor has a medical record indicating that she was treated 
for Chlamydia 14 months ago.  No follow-up testing was performed at the time of 
treatment.  The medical record serves as evidence that she received treatment 
more than 12 months ago.  Since the medical record does not include information 
that a follow-up test was performed after treatment and was negative, there is no 
evidence that the treatment was successful.  However, a current negative test for 
Chlamydia (as part of the current donor testing) may serve as evidence that the 
treatment that occurred more than 12 months ago was successful. 
 
19. Persons who have been diagnosed with vCJD or any other form of CJD (Refs. 
3 and 75). 
 
Note:  Numbers 19 to 26 in this section are designed to screen for TSEs, including 
CJD and vCJD.  If the living donor or the individual knowledgeable about the donors 
medical and travel history is not familiar with the term Creutzfeldt-Jakob Disease 
or variant Creutzfeldt-Jakob Disease, you may try to describe those in laymans 
terms.  If the person being interviewed is still not familiar with those terms, you may 
consider the lack of familiarity with those terms as a negative response to questions 
using those terms. 
 
20. Persons who have been diagnosed with dementia or any degenerative or 
demyelinating disease of the central nervous system or other neurological disease 
of unknown etiology (Refs. 3 and 75).  Potential donors who have a diagnosis of 
delirium (e.g., delirium caused by toxic/metabolic diseases or recent head trauma) 
would not necessarily be considered to have a diagnosis of dementia and should 
be evaluated by the Medical Director.  (HCT/Ps from donors with dementia 
confirmed by gross and microscopic examination of the brain to be caused by 
cerebrovascular accident or brain tumor and who are confirmed not to have 
evidence of TSE on microscopic examination of the brain may be acceptable 
based on an evaluation by the Medical Director). 
 
21. Persons who are at increased risk for CJD (Refs. 3 and 75).  Donors are 
considered to have an increased risk for CJD if they have received a non-synthetic 
dura mater transplant, human pituitary-derived growth hormone, or have one or 
more blood relatives diagnosed with CJD (see criterion 22 of this section).  
 
18 
  Contains Nonbinding Recommendations 
 
22. Persons who have a history of CJD in a blood relative (Refs. 3 and 75) unless: 
 
  The diagnosis of CJD was subsequently found to be an incorrect 
diagnosis;  
  The CJD was iatrogenic; or  
  Laboratory testing (gene sequencing) shows that the donor does not have a 
mutation associated with familial CJD. 
 
23. Persons who spent three months or more cumulatively in the United Kingdom 
(U.K.) (see Appendix 5) from the beginning of 1980 through the end of 1996 
(Refs. 3 and 75). 
 
24. Persons who are current or former U.S. military members, civilian military 
employees, or dependents of a military member or civilian employee who resided 
at U.S. military bases in Northern Europe (Germany, Belgium, and the 
Netherlands) for 6 months or more cumulatively from 1980 through 1990, or 
elsewhere in Europe (Greece, Turkey, Spain, Portugal, and Italy) for 6 months or 
more cumulatively from 1980 through 1996 (Refs. 3 and 75).   
 
25. Persons who spent 5 years or more cumulatively in Europe (see Appendix 5) 
from 1980 until the present (note this criterion includes time spent in the U.K. 
from 1980 through 1996) (Refs. 3 and 75). 
 
26. Persons who received any transfusion of blood or blood components in the 
U.K. or France between 1980 and the present (Refs. 3 and 75). 
 
27. Persons or their sexual partners who were born or lived in certain countries in 
Africa (Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, 
Gabon, Niger, or Nigeria) after 1977 (Refs. 66 and 76) (risk factor for HIV group 
O).   
 
28. Persons who have received a blood transfusion or any medical treatment that 
involved blood in the countries listed in criterion 27, after 1977 (Refs. 66 and 76) 
(risk factor for HIV group O). 
 
Note:  Establishments utilizing an HIV-1/2 antibody donor screening test that has 
been licensed by FDA and is specifically labeled in the Intended Use Section of 
the package insert as sensitive for detection of HIV group O antibodies may 
delete items 27 and 28 from their screening procedures.  If such establishments 
continue to ask items 27 and 28, the donor eligibility may be based on the results 
of the donor screening test regardless of the answers to items 27 and 28.  
Establishments that do not utilize an HIV antibody donor screening test that has 
been licensed by FDA for detection of HIV group O antibodies should continue to 
ask these items. 
 
19 
  Contains Nonbinding Recommendations 
 
29. Persons who are xenotransplantation product recipients or intimate contacts of 
a xenotransplantation product recipient (Ref. 77).  
 
a.  For the purpose of this document, we define the following terms: 
 
i.  Xenotransplantation is any procedure that involves the transplantation, 
implantation, or infusion into a human recipient of either:  (1) live cells, 
tissues, or organs from a nonhuman animal source; or (2) human body 
fluids, cells, tissues, or organs that have had ex vivo contact with live 
nonhuman animal cells, tissues, or organs. 
 
ii.  Xenotransplantation products include live cells, tissues, or organs used 
in xenotransplantation.  Biological products, drugs, or medical devices 
sourced from nonliving cells, tissues or organs from nonhuman animals, 
including but not limited to porcine insulin and porcine heart valves, are 
not considered xenotransplantation products. 
 
iii. Xenotransplantation product recipient means a person who undergoes 
xenotransplantation. 
  
iv.  Intimate contact of a xenotransplantation product recipient means a 
person who has engaged in activities that could result in intimate exchange 
of body fluids, including blood or saliva, with a xenotransplantation 
product recipient.  Examples of intimate contacts include sexual partners, 
household members who share razors or toothbrushes, and health care 
workers or laboratory personnel with repeated percutaneous, mucosal, or 
other direct exposures.  We do not consider sharing of housing or casual 
contact, such as hugging or kissing without the exchange of saliva, to be 
intimate contact.   
 
b.  To determine whether a potential HCT/P donor is a xenotransplantation 
product recipient, or is the intimate contact of a person who has received a 
xenotransplantation product, you should determine whether the potential 
donor, his/her sexual partner, or any member of his/her household has ever 
had a transplant or other medical procedure that involved being exposed to 
live cells, tissues, or organs from an animal.  If the potential donor or his/her 
sexual partner is the recipient of a xenotransplantation product, you should 
defer the donor.  If the potential donor is a member of the xenotransplantation 
product recipients household, you should determine whether the potential 
donor has been exposed to blood, saliva, or other body fluids from the 
xenotransplantation product recipient.  If the potential donor has been exposed 
to any of these fluids, you should defer the donor.    
 
Note:  There are circumstances in which it might not be necessary to defer a 
potential HCT/P donor who is an intimate contact of a recipient of 
certain xenotransplantation products.  For example, an advisory 
20 
  Contains Nonbinding Recommendations 
 
committee recommended and we concur that intimate contacts of 
persons who have received the product EpicelTM do not need to be 
deferred from blood donation, because the risk of zoonotic 
transmission from this product is minimal as the non-human animal 
cells used in the manufacture of this product originate from a well-
characterized cell line.  For this same reason, intimate contacts of 
EpicelTM recipients need not be deferred from tissue donation (Ref. 78) 
(Note:  You should defer EpicelTM recipients from tissue donation). 
 
F.  What clinical evidence do I look for when screening a donor? 
 
You must review relevant medical records for clinical evidence of relevant 
communicable disease agents and diseases ( 1271.75).  For cadaveric donors, you 
should: 
 
  Determine whether an autopsy was not performed due to a perceived risk of 
transmission of a communicable disease, or,  
  If an autopsy was performed, whether any special precautions were taken that 
would suggest there was special concern over the risk of transmission of a 
communicable disease from the donor.   
 
You should look for the following examples of clinical evidence of relevant 
communicable disease.  Except as noted in this section and in accordance with  
1271.75(d), you should determine to be ineligible any potential donor who exhibits one 
or more of the following examples of clinical evidence of relevant communicable 
disease.   
 
1.  HIV infection: 
 
  A prior positive or reactive screening test for HIV; 
  Unexplained weight loss; 
  Unexplained night sweats;  
  Blue or purple spots on or under the skin or mucous membranes typical of 
Kaposis sarcoma; 
  Disseminated lymphadenopathy (swollen lymph nodes) for longer than 
one month; 
  Unexplained temperature of  > 100.5oF (38.06oC) for more than 10 days; 
  Unexplained persistent cough or shortness of breath; 
  Opportunistic infections; 
  Unexplained persistent diarrhea; and/or 
  Unexplained persistent white spots or unusual blemishes in the mouth 
(Ref. 79). 
 
21 
  Contains Nonbinding Recommendations 
 
2.  Hepatitis infection:  
 
  A prior positive or reactive screening test for hepatitis B virus or hepatitis 
C virus; 
  Unexplained jaundice; 
  Unexplained hepatomegaly; and/or 
  Past diagnosis of clinical, symptomatic viral hepatitis after the 11th 
birthday (Ref. 70 and 71), unless evidence from the time of illness 
documents that the hepatitis was identified as caused by hepatitis A virus, 
EBV, or CMV. 
 
Note:  Records of the following laboratory data might assist you in making the 
donor-eligibility determination in the face of an inconclusive history of hepatitis 
infection: alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
bilirubin or prothrombin time (Ref. 71).  If these tests are abnormal, but a cause 
other than viral hepatitis was established, we do not recommend that you defer the 
donor. 
 
3.  Syphilis, Chlamydia trachomatis, or Neisseria gonorrhea infection (Screening 
and donor deferral for Chlamydia trachomatis and Neisseria gonorrhea required 
only for reproductive donors): 
 
  Persons who have had or have been treated for syphilis, Chlamydia 
trachomatis, or Neisseria gonorrhea in the preceding 12 months (Ref. 79).  
We do not recommend deferral of donors who have had or have been 
treated for syphilis, Chlamydia trachomatis, or Neisseria gonorrhea more 
than 12 months ago, if evidence is presented that treatment occurred more 
than 12 months ago and was successful (Ref. 80).  
 
4.  Vaccinia infection (see IV. E., 13. and 14. for specific deferral criteria for 
recent smallpox vaccination or acquired vaccinia infection by contact with 
someone who received the smallpox vaccine): 
 
  Recent smallpox vaccination; 
  Eczema vaccinatum;  
  Vesicular rash indicative of generalized vaccinia in a person who has had 
recent smallpox immunization or who is a contact of someone with recent 
smallpox immunization, as specified in IV. E. 14.;  
  Progressive necrosis in an area of vaccination consistent with vaccinia 
necrosum; 
  Postvaccinial encephalitis; and/or 
  Vaccinial keratitis (Ref. 12). 
 
22 
  Contains Nonbinding Recommendations 
 
5.  WNV infection (Refs. 5, 6, and 7).  Because signs and symptoms of WNV can 
be nonspecific, you should consider the following clinical evidence in light of 
other information obtained about the donor in making a donor eligibility 
determination.   
 
  Mild symptoms might include fever, headache, body aches, or eye pain;  
o  mild symptoms might also occasionally be accompanied by a skin 
rash on the trunk of the body; or  
o  swollen lymph glands. 
  Severe illness; 
o  severe illness might include encephalitis, meningitis, 
meningoencephalitis, and acute flaccid paralysis;  
o  signs and symptoms of severe illness might include headache, high 
fever, neck stiffness, stupor, disorientation, coma, tremors, 
convulsions, and muscle weakness or paralysis. 
 
6.  Sepsis (includes, but is not limited to, bacteremia, septicemia, sepsis 
syndrome, systemic infection, systemic inflammatory response syndrome (SIRS) 
or septic shock):  
 
In reference to deceased donors, if any of these conditions is specifically diagnosed in 
the medical records during a hospital stay immediately preceding death, you should 
determine the donor to be ineligible (see section IV.E. criterion 12 of this document).  
If a living donor appears healthy, the donor usually does not need to be evaluated for 
sepsis. 
 
Sepsis may be described by the following clinical evidence (Ref. 84).  You should 
consider these signs in light of other information obtained about the donor in making 
a donor eligibility determination. 
 
  Clinical evidence of infection; and 
  Two or more of the following systemic responses to infection if unexplained:  
o  Temperature of >100.4o F (38o C); 
o  Heart rate >90 beats/min; 
o  Respiratory rate >20 breaths/min or PaCO2 <32; or 
o  WBC >12,000 cells/mm3, < 4,000 cells/mm3, or >10% immature 
(band) forms. 
  More severe signs of sepsis include unexplained hypoxemia, elevated lactate, 
oliguria, altered mentation, and hypotension.   
  Positive (pre-mortem) blood cultures might be associated with the above 
signs. 
23 
  Contains Nonbinding Recommendations 
 
7.  HTLV infection (Screening and donor deferral for HTLV required only for 
viable, leukocyte-rich HCT/P donors): 
 
  A prior positive or reactive screening test for HTLV; 
  Unexplained paraparesis; and/or 
  Adult T-cell leukemia (Refs. 85 and 86). 
 
G. What physical evidence do I look for?  
 
Relevant medical records ( 1271.3(s)) include the report of the physical assessment of a 
cadaveric donor ( 1271.3(o)) or the physical examination of a living donor.  For living 
donors, you may examine only those parts of the body that are necessary to evaluate for 
RCDADs based upon relevant donor history that has been obtained during the interview 
and review of available records.  You may rely on records of a recent report of a physical 
examination by other health professionals.  You should review the records of the physical 
assessment or physical examination for any of the following signs that may indicate high-
risk behavior for or infection with a relevant communicable disease.  Some of the 
following are not physical evidence of HIV, hepatitis, syphilis, or vaccinia but rather are 
indications of high-risk behavior associated with these diseases and would increase the 
donors relevant communicable disease risk.  Except as noted in this section and in 
accordance with  1271.75(d), you should determine to be ineligible any potential donor 
who exhibits one or more of the following examples of physical evidence of relevant 
communicable disease or high-risk behavior associated with these diseases (see Refs. 12 
and 87).     
 
1.  Physical evidence for risk of sexually transmitted diseases such as genital 
ulcerative disease, herpes simplex, chancroid (you should consider these signs in 
light of other information obtained about the donor in making a donor eligibility 
determination) (seen in HIV, Hepatitis B virus, Chlamydia trachomatis, and 
Neisseria gornorrheae). 
 
2.  Physical evidence for risk of, or evidence of syphilis.  
 
3.  For a male donor, physical evidence of anal intercourse including perianal 
condyloma (seen in HIV and Hepatitis B). 
 
4.  Physical evidence of nonmedical percutaneous drug use such as needle tracks; 
your examination should include examination of tattoos, which might be covering 
needle tracks (seen in HIV, Hepatitis B and Hepatitis C). 
 
5.  Physical evidence of recent tattooing, ear piercing, or body piercing.  Persons 
who have undergone tattooing, ear piercing, or body piercing in the preceding 12 
months, in which sterile procedures were not used (e.g., contaminated instruments 
and or/ink were used), or instruments that had not been sterilized between uses 
were used (seen in HIV, Hepatitis B and Hepatitis C).  
 
24 
  Contains Nonbinding Recommendations 
 
6.  Disseminated lymphadenopathy (seen in HIV). 
 
7.  Unexplained oral thrush (seen in HIV). 
 
8.  Blue or purple spots consistent with Kaposis sarcoma (seen in HIV).  
 
9.  Unexplained jaundice, hepatomegaly, or icterus (seen in Hepatitis B and 
Hepatitis C).  
 
Note:  Hepatomegaly may not be apparent in a physical assessment unless an 
autopsy is performed. 
 
10. Physical evidence of sepsis, such as unexplained generalized rash or fever. 
 
11. Large scab consistent with recent history of smallpox immunization. 
 
12. Eczema vaccinatum (seen in vaccinia). 
 
13. Generalized vesicular rash (generalized vaccinia). 
 
14. Severely necrotic lesion consistent with vaccinia necrosum. 
 
15. Corneal scarring consistent with vaccinial keratitis. 
 
 
V.  DONOR TESTING:  GENERAL ( 1271.80) 
 
A.  What requirements apply to laboratories performing donor testing for relevant 
communicable disease agents or diseases? 
 
1.  Under  1271.1, you must be registered with FDA.  
 
2.  Under  1271.80(c): 
 
  You must use appropriate FDA licensed, approved or cleared donor 
screening tests, if such tests are available, in accordance with the 
manufacturers instructions.   
  You must use a donor screening test specifically labeled for cadaveric 
specimens instead of a more generally labeled donor screening test when 
applicable and when available.   
  You must be certified to perform such testing on human specimens either 
under the Clinical Laboratory Improvement Amendments (CLIA) or you 
must meet equivalent requirements as determined by the Centers for 
Medicare and Medicaid Services.  Examples of the latter include 
laboratories that have been accredited by accrediting organizations 
approved by CMS.  Certain states are exempt under CLIA because CMS 
25 
  Contains Nonbinding Recommendations 
 
has found their state programs to be in compliance with CLIA standards.4  
Information about the CLIA program is available at the website:  
http://www.cms.hhs.gov/clia/.  
 
3.  Under  1271.55(d), you must maintain documentation of results and 
interpretation of all testing for at least 10 years.   
 
B.  What type of test must I use?  
 
You must test using an appropriate FDA-licensed, approved, or cleared donor screening 
test (if applicable to your HCT/P and available) in accordance with the manufacturers 
instructions to adequately and appropriately reduce the risk of transmission of the 
relevant communicable disease agent or disease ( 1271.80(c)). 
 
  You should choose a test that is adequate, appropriate and available for detecting 
the relevant communicable disease agent or disease.  We list tests that we 
currently consider to meet the requirements in  1271.80(c) in section VI. of this 
document. 
  In some instances, you may need to conduct more than one test to adequately and 
appropriately test for a single communicable disease agent or disease.  For 
example, to test for HIV-1, it is appropriate to use a test that detects viral nucleic 
acid (e.g., a nucleic acid test) and a test that detects antibody to HIV-1 (e.g., an 
enzyme immunoassay).  If HIV-1 infection is present, each test may be reactive at 
different times during the course of the disease. 
  If you are testing a specimen of cadaveric blood (i.e., taken from a donor whose 
heartbeat has ceased), you must use a donor screening test specifically labeled for 
cadaveric specimens instead of a more generally labeled donor screening test, 
when such a test is applicable and available ( 1271.80(c)).  You can find a list of 
donor screening tests that have been licensed for use with cadaveric specimens on 
CBERs website: http://www.fda.gov/cber/tissue/prod.htm.  We intend to update 
the website periodically as additional tests are licensed, cleared or approved for 
this use and become available. 
 
C.  How do I perform the test and interpret test results? 
 
You must perform the test according to the manufacturers instructions in the test kits 
package insert ( 1271.80(c)).  The manufacturers instructions also provide information 
about interpretation of test results. 
 
                                                 
 
4 CMS has approved the following accrediting organizations:  AABB, the American Osteopathic Association, the 
American Society for Histocompatibility and Immunogenics, the College of American Pathologists, COLA, and the 
Joint Commission on Accreditation of Healthcare Organizations.  CMS has determined two states to be exempt: 
New York and Washington.  Since these lists are subject to change, we recommend that you consult CMS for the 
most current information.   http://www.cms.hhs.gov/clia/. 
26 
  Contains Nonbinding Recommendations 
 
Some HCT/P establishments routinely rely solely on the test results obtained by an organ 
procurement organization (OPO), while other establishments routinely perform their own 
donor testing with the awareness that OPOs are performing donor testing on the same 
donors.  The use of an appropriate screening test, performed in accordance with the 
manufacturers instructions for use, would satisfy the requirements of  1271.80 and 
1271.85.  However, because of testing practices related to organ donor screening as 
described by the Centers for Disease Control and Prevention (CDC), some OPOs may run 
an enzyme immunoassay donor screening test initially in triplicate (Ref. 18).   The 
manufacturers instructions for use of HCT/P donor screening tests currently do not 
provide instructions for initial triplicate testing, interpretation of test results of such 
testing, or for retesting after an initially reactive test when the tests are initially run in 
triplicate.  Therefore, if initial tests are run in triplicate and one or more reactive results 
are obtained, manufacturers do not provide instructions on determining whether the 
sample is actually (repeatedly) reactive.  Accordingly, if you engage an OPO to perform 
testing for you or if you routinely perform your own tests but are aware that an OPO is 
also performing tests on that donor, and that OPO performs initial testing in triplicate, 
then under  1271.50 and 1271.150 you must obtain and review the results of all three 
tests performed by that OPO.  If any of those initial tests is reactive or positive, then the 
donor would not be eligible to donate. 
 
D.  If a donor is one month of age or younger, from whom must I collect a 
specimen?  
 
If a donor is one month of age or younger, you must collect and test a specimen from the 
birth mother instead of the donor ( 1271.80(a)).  The specimen for testing from the birth 
mother must be collected within seven days of donation by the infant ( 1271.80(b)), 
unless the donation consists of peripheral blood stem/progenitor cells or bone marrow 
according to 1271.80(b)(1).  If a specimen from the birth mother of a donor one month of 
age or younger is unavailable, the donor is ineligible.  Specimens collected for any infant 
donor more than one month of age, including adopted infants, should be collected from 
the donor rather than the birth mother.   
 
E.  When do I collect a specimen for testing? 
 
You must collect the donor specimen for testing at the same time as cells or tissue are 
recovered from the donor, or within seven days before or after the recovery of cells and 
tissue  ( 1271.80(b)), with some exceptions as described in this section.  As you are 
permitted under  1271.80(b) to collect the donor specimen up to seven days before 
recovery of cells or tissues, you may use a premortem specimen to test a cadaveric donor, 
as long as the specimen is collected within that timeframe.  
 
In the case of donation of hematopoietic stem/progenitor cells (HPCs) obtained from 
peripheral blood or bone marrow (if not excepted under  1271.3(d)(4)), we realize that 
the recipient may begin myeloablative chemotherapy more than 7 days before the 
transplant.  Therefore, the identified allogeneic donor might need to be qualified before 
27 
  Contains Nonbinding Recommendations 
 
this time, including screening and testing of the donor for relevant communicable 
diseases.  In this situation, you may collect the donor specimen used for communicable 
disease testing up to 30 days before donation ( 1271.80(b)(1)).   
 
In the case of donation of oocytes that do not undergo a period of cryopreservation prior 
to implantation, an oocyte donor might need to be qualified before the 7 days prior to 
donation due to the time necessary for receiving hormonal stimulation.  In this situation, 
you may collect the donor specimen used for communicable disease testing up to 30 days 
before donation ( 1271.80(b)(1)). 
 
Although there is no requirement that specifies when to test the collected specimen, you 
should perform testing as soon as possible after collection and in accordance with the 
time limits stated in the manufacturers instructions for use of the test kit. 
 
F.  May I test a specimen from a donor who has undergone transfusion or infusion?  
 
Transfusion or infusion might dilute plasma, making test results unreliable (Refs. 18 and 
88).  You may test a specimen taken before the transfusion or infusion and up to seven 
days before recovery of cells or tissue, or if an adequate pre-transfusion/infusion 
specimen is not available, you may use an appropriate algorithm to determine whether 
plasma dilution is or is not sufficient to affect test results.  In the absence of an 
appropriate specimen to test under either of these options, you must determine the donor 
to be ineligible ( 1271.80(d)(2)). 
 
For adult donors who have suffered blood loss sufficient to require fluid replacement, 
certain volumes of transfusions and/or infusions (described in section V.F.1. of this 
document) should be suspected of affecting test results.  Blood loss might occur 
internally or externally.  For donors 12 years of age or younger, you should suspect that 
any transfusion or infusion might affect test results regardless of blood loss.  There might 
be other clinical situations involving transfusion or infusion that should also be suspected 
of affecting test results.  Autologous blood removed pre-operatively or peri-operatively 
and reinfused during the same surgical procedure would not need to be included in 
plasma dilution calculations.   
 
1.  Adult Donor ( 1271.80(d)(2)(ii)(A)) 
 
In accordance with  1271.80(d)(2)(ii)(A), you must suspect plasma dilution 
sufficient to affect the results of communicable disease agent testing where blood 
loss is known or suspected in a donor over 12 years of age in any of the following 
situations: 
 
a.  The donor received a transfusion or infusion of more than 2000 milliliters 
of blood (e.g., whole blood or red blood cells) or colloids either:  (i) within the 
48 hours immediately preceding the collection of a pre-mortem specimen for 
testing; or (ii) within the 48 hours immediately preceding death, if the 
specimen for testing is collected post-mortem, whichever occurred earlier.  
28 
  Contains Nonbinding Recommendations 
 
 
b.  The donor received more than 2000 milliliters of crystalloids within either: 
(i) the one hour immediately preceding the collection of a pre-mortem 
specimen for testing; or (ii) within the one hour immediately preceding death, 
if the specimen for testing is collected post-mortem, whichever occurred 
earlier. 
 
c.  The donor received more than 2000 milliliters of any combination of 
whole blood, red blood cells, colloids, and/or crystalloids within the 
applicable time frames set out in paragraphs (a) and (b) in this section.   
 
2.  Pediatric Donor ( 1271.80(d)(2)(ii)(B)) 
 
In accordance with  1271.80(d)(2)(ii)(B), you must suspect plasma dilution 
sufficient to affect the results of communicable disease agent testing, regardless of 
the presence or absence of blood loss, in a donor 12 years of age or under, in any 
of the following situations. 
 
a.  Any transfusion of blood or colloids:  (i) within the 48 hours immediately 
preceding the collection of a pre-mortem specimen for testing; or (ii) within 
the 48 hours immediately preceding death, if the specimen is collected post-
mortem, whichever occurred earlier. 
 
b.   Any crystalloids:  (i) within the one hour immediately preceding the 
collection of a pre-mortem specimen for testing; or (ii) within the one hour 
immediately preceding death, if the specimen is collected post-mortem, 
whichever occurred earlier. 
 
3.  Other Clinical Situations 
 
We cannot provide guidance that anticipates every possible clinical situation 
where plasma dilution might affect test results.  As the establishment that collects 
donor specimens for testing, you might be aware of additional circumstances in 
which plasma dilution might affect test results.  Your SOPs should identify any 
additional circumstances where you believe plasma dilution might have occurred, 
and you should use a pre-transfusion/infusion specimen or apply an algorithm in 
those instances.   
 
Examples:  In the following situations, the donor has received a transfusion or 
infusion, but circumstances are not otherwise consistent with the examples set out 
in sections V.F.1. and 2. of this document.  Nevertheless, you should consider test 
results on specimens collected at the time of donation to be potentially unreliable, 
triggering the need to test a pre-transfusion or pre-infusion sample, or to apply the 
algorithm, in the following circumstances: 
 
29 
  Contains Nonbinding Recommendations 
 
  A donor who has previously had blood loss, stabilizes, then expires, but 
has received fluids in the 48 hours before specimen collection; 
  A donor who is obese;  
  A donor who in the absence of bleeding may have received large amounts 
of infusions which the medical director or designee believes may affect 
test results;  
  A donor who weighs less than 45 kilograms or more than 100 kilograms.  
 
For situations falling outside those described in your SOPs, but where 
plasma dilution is still suspected, your SOPs should indicate how the 
situation would be handled (for example, by consulting the medical 
director).  
 
4.  Pre-Transfusion/Infusion Specimen 
 
As part of establishing procedures for all steps in testing in accordance with  
1271.47(a), establishments making donor eligibility determinations must have 
SOPs that define those elements necessary to determine whether a pre-
transfusion/infusion blood specimen is adequate for infectious disease testing 
(e.g., the amount of hemolysis, storage conditions, and age of the specimen).  
Testing laboratories must perform tests in accordance with the manufacturers 
instructions ( 1271.80(c)), including any instructions concerning factors that 
might affect specimen stability.  
  
5.  Algorithms 
 
An appropriate algorithm must evaluate the fluid volumes administered in the 48 
hours before collecting the specimen from the donor and show that plasma 
dilution sufficient to affect test results has not occurred ( 1271.80(d)(2)(i)(B)).  
A plasma dilution of greater than 50% (1:2 dilution) could make test results 
unreliable.  Therefore, you should use a method that compares the actual fluid 
volumes administered with both the donors plasma and blood volumes to assess 
whether a greater than 50% dilution has occurred. 
 
If the algorithm shows that greater than a 50% dilution has occurred, then you 
should not use the post-transfusion/infusion specimen for testing.  You should not 
use further procedures that attempt to qualify the ineligible specimen.   
 
When calculating blood and plasma volumes for donors in the 45 to 100 kilogram 
range, where there is blood loss with replacement, you should calculate and assess 
both blood volume and plasma volume as follows: 
 
  Determine the blood volume in milliliters (mL) by dividing the body 
weight in kilograms (kg) by 0.015, or alternatively by multiplying the 
body weight in kilograms by 70 mL/kg. 
30 
  Contains Nonbinding Recommendations 
 
  Determine the plasma volume in milliliters (mL) by dividing the body 
weight in kilograms (kg) by 0.025, or alternatively by multiplying the 
body weight in kilograms by 40 mL/kg.   
 
(See Appendices 1, 2, and 3)  
 
G. What are some useful definitions related to hemodilution? 
 
1.  Blood component means a product containing a part of human blood separated 
by physical or mechanical means ( 1271.3(i)). 
 
2.  Colloid means:  (1) a protein or polysaccharide solution, such as albumin, 
dextran, or hetastarch, that can be used to increase or maintain osmotic (oncotic) 
pressure in the intravascular compartment; or (2) blood components such as 
plasma and platelets ( 1271.3(j)). 
 
3.  Crystalloid means an isotonic salt and/or glucose solution used for electrolyte 
replacement or to increase intravascular volume, such as saline solution, Ringers 
lactate solution, 5 percent dextrose in water ( 1271.3(k)), or total parenteral 
nutrition (TPN) (Ref. 89). 
 
4.  Plasma dilution means a decrease in the concentration of the donors plasma 
proteins and circulating antigens or antibodies resulting from the transfusion of 
blood or blood components and/or infusion of fluids ( 1271.3(p)). 
 
 
VI.  DONOR TESTING:  SPECIFIC REQUIREMENTS ( 1271.85) 
 
A.  For what diseases must I test all donors of HCT/Ps, and what tests should I use?   
 
You must test all donors of HCT/Ps, unless subject to an exemption in  1271.90(a), for 
the diseases listed in section VI.A.1. through 5., as required in  1271.85(a).  You must 
use an FDA-licensed, approved, or cleared screening test, as described in section V. ( 
1271.80(c)).  Current FDA-licensed donor screening tests for HIV, Hepatitis B, Hepatitis 
C, and HTLV are listed at the website:  www.fda.gov/cber/products/testkits.htm.  You 
may also check this website:  http://www.fda.gov/cber/tissue/prod.htm for links to 
HCT/P-related, FDA-licensed, approved or cleared donor screening tests.  The tests listed 
in this section adequately and appropriately reduce the risk of transmission of relevant 
communicable disease.  Our recommendations on specific tests may change in the future 
due to technological advances or evolving scientific knowledge:  
 
1.  HIV, type 1 (FDA-licensed screening test either for anti-HIV-1 or 
combination test for anti-HIV-1 and anti-HIV-2 (Refs. 79 and 90); and FDA-
licensed screening NAT test for HIV-1, or combination NAT); (establishments 
31 
  Contains Nonbinding Recommendations 
 
not utilizing an FDA-licensed screening test that tests for group O antibodies must 
evaluate donors for risk associated with HIV group O infection as described in 
section IV.E.27. and 28. (Refs. 66 and 76)) 
 
2.  HIV, type 2 (FDA-licensed screening test either for anti-HIV-2 or 
combination test for anti-HIV-1 and anti-HIV-2) (Refs. 79 and 90); 
 
3.  HBV (FDA-licensed screening test for Hepatitis B surface antigen (HBsAg) 
(Ref. 72) and for total antibody to Hepatitis B core antigen (anti-HBc)(IgG and 
IgM) (Refs. 91 through 98);     
 
4.  HCV (FDA-licensed screening test for anti-HCV5; and FDA-licensed 
screening NAT test for HCV, or combination NAT) (Refs. 2, 69, 90, 91, and 99); 
and 
 
5.  Treponema pallidum (FDA-cleared screening test for syphilis or FDA-cleared 
diagnostic serologic test for syphilis6) (Refs. 80 and 100).   
 
As an exception for syphilis test results under  1271.80(d)(1), you may determine to 
be eligible a donor whose specimen tests positive or reactive on a non-treponemal 
screening test for syphilis and negative or nonreactive on a specific treponemal 
confirmatory test (e.g., fluorescent treponemal antibody with absorption test (FTA-
ABS), so long as all other required testing and screening are negative or nonreactive.  
A donor whose specimen tests positive or reactive on either a specific treponemal 
confirmatory test for syphilis or on a treponemal screening test is not eligible.  If a 
cadaveric specimen is too hemolyzed to interpret the Rapid Plasma Reagin (RPR) test 
result, you should use another test, such as the FTA-ABS test result. 
 
Discussion of Syphilis Assays  
 
a.  Nontreponemal assays, such as the Venereal Disease Research Laboratory 
(VDRL) test, the RPR test, and the Automated Reagin Test (ART), detect 
nonspecific antibodies (Reagin) to an antigen called cardiolipin present in host 
tissues as well as in treponemes.  These assays are useful in monitoring the 
progression of disease and response to therapy.  However, positive or reactive 
tests might be due to diseases other than syphilis (i.e., biological false 
positives).  Samples that give positive or reactive results using nontreponemal 
assays may be retested using a treponemal-based assay as a confirmatory 
assay, such as the FTA-ABS.  Nontreponemal test results usually become 
nonreactive within a year or two after successful treatment of syphilis.  
                                                 
 
5 On  July 22, 2004, FDA approved the Abbott Laboratories Supplement to their Biological License Application for 
Hepatitis C Virus Encoded Antigen to modify the intended use of the Abbott HCV EIA 2.0 to include the testing of 
cadaveric specimens.  This specifically labeled test kit is now available for commercial use. 
6 For purposes of this guidance, we consider FDA-cleared diagnostic serological tests to be adequate for use in 
donor screening for syphilis. 
32 
  Contains Nonbinding Recommendations 
 
 
b.  Treponemal assays incorporate specific treponemal antigens into the 
testing system and detect specific antibodies to these antigens.  With a few 
exceptions, unlike nontreponemal assays, results of tests for treponemal 
antigens remain positive or reactive for specific antibodies throughout an 
individuals life, even after successful treatment for syphilis.  Treponemal 
assays include the FTA-ABS, the Treponema pallidum immobilization test 
(TPI) and the T. pallidum hemagglutination assay (TPHA).  Since both types 
of assays detect antibodies, they might not identify some very early syphilis 
infections before antibodies to either cardiolipin or specific treponemal 
antigens have appeared (Ref. 100).  
 
c.  Serological tests for syphilis may be either non-treponemal or treponemal-
based assays.  Because of the potential for false-positive results in non-
treponemal assays,  1271.80(d)(1) provides that a specific treponemal 
confirmatory test, such as FTA-ABS, may be used to determine the syphilis 
status of an HCT/P donor when a positive result on a non-treponemal assay is 
obtained.  If the confirmatory test is positive or reactive, the donor is 
ineligible.    
 
6.  p24 Antigen Tests:  We are aware that HIV-1 p24 antigen tests are not readily 
available because they are not currently being manufactured.  Therefore, you are 
not required to use the HIV-1 p24 antigen test for HCT/P donors.  There are 
currently more sensitive tests available (Refs. 90 and 101). 
 
Discussion About Additional Testing 
 
You or someone else might perform additional testing not listed in section VI.A.  If you 
perform donor testing for relevant communicable diseases using tests in addition to those 
listed in section VI.A.1. through 5., VI.B., and VI.C., as applicable, or if you are aware 
that other establishments are performing such tests and the test results are available, such 
test results must be included in the donors relevant medical record (see  1271.3).  
Because these test results are part of the medical record, you must consider any results 
from those tests when you make a donor eligibility determination ( 1271.75(a)).  By 
available we mean that the test result exists or is obtainable within a reasonable amount 
of time.  A reasonable amount of time is a period of time that would not compromise 
the utility of the tissue. 
 
Example:  An eye bank is aware that a tissue bank performs an investigational 
NAT assay on a shared donor.  The eye bank is not informed of the test results 
until after the corneas need to be released in order to maintain their utility.  The 
eye bank does not have to wait for the investigational NAT results before 
releasing the corneas.  The eye bank should inform the consignee that the 
investigational NAT results are pending, and subsequently report the result. 
 
33 
  Contains Nonbinding Recommendations 
 
Confirmatory tests:  You should consider performing confirmatory tests when a positive 
or reactive screening test result is received for such purposes as donor counseling or 
investigating discordant test results.  However, if you perform a confirmatory test, 
negative or nonreactive results on a confirmatory test would not override a positive or 
reactive screening test (except for syphilis tests as previously described in this section). 
 
Example:  A potential donors specimen tests reactive for antibody to HCV.  
However, a confirmatory test (e.g., radioimmunoblot assay) is negative.  The 
donor would be considered ineligible despite the negative confirmatory test. 
 
Hepatitis B surface antibody (anti-HBs) test:  If you obtain a positive or reactive anti-
HBs test and other markers for Hepatitis B infection are negative or non-reactive, the 
donor may be eligible. 
 
Example:  Your contract laboratory routinely performs three different tests for 
HBV: Hepatitis B surface antigen (HBsAg) test, Hepatitis B core antibody (anti-
HBc) test, and anti-HBs test.  You have a potential donor who is negative or 
nonreactive for HBsAg and anti-HBc, but positive or reactive for anti-HBs.  The 
presence of anti-HBs alone would not disqualify the donor, because it usually is 
an indication of vaccination against Hepatitis B.  However, in this situation, if the 
anti-HBc were also positive or reactive, the donor is ineligible.  Data suggests that 
such results can be associated with infectivity (Refs. 92 through 98). 
 
B.  For what additional diseases must I test donors of viable, leukocyte-rich cells or 
tissue and what tests should I use?  
 
1.  You must test donors of viable, leukocyte-rich cells or tissue for the following 
diseases, in addition to those listed in section VI.A. of this document ( 
1271.85(b)).  You must use an FDA-licensed, cleared, or approved donor 
screening test where such a test is available ( 1271.80(c)).  A list of currently 
licensed donor screening tests for HCT/Ps can be found at the website:  
http://www.fda.gov/cber/tissue/prod.htm.   
 
The tests listed in this section adequately and appropriately reduce the risk of 
transmission of relevant communicable diseases: 
 
a.  Human T-lymphotropic virus, types I and II (FDA-licensed screening test 
for anti-HTLV I/II) (Refs. 85 and 86). 
 
b.  Cytomegalovirus (FDA-cleared screening test for anti-CMV) (total IgG 
and IgM).  
  
Special note on CMV:  CMV is not a relevant communicable disease agent or 
disease.  However, establishments are required to test donors of viable, leukocyte-
rich cells or tissues for CMV.  A donor who tests positive or reactive for CMV 
(total antibody) is not necessarily ineligible to donate HCT/Ps.  You must 
34 
  Contains Nonbinding Recommendations 
 
establish and maintain an SOP regarding donors whose specimens test positive or 
reactive for CMV ( 1271.85(b)(2)).  This latter requirement only applies to 
establishments that make available for distribution HCT/Ps for which CMV 
testing is required.    
 
Establishments should include procedures in their SOPs for communicating test 
results of donors who are positive or reactive for CMV antibody (total).  The SOP 
should at least specify how the CMV test results should be communicated to the 
physician responsible for accepting the HCT/P.  For example, the SOP should 
require that this information appear in materials accompanying the HCT/P, so that 
physicians may rely on this information to make informed decisions about the use 
of an HCT/P in a particular recipients situation.  An establishments SOPs may 
also clarify that repeated testing of donors who are positive or reactive for CMV 
antibody (total) is unnecessary once it is established that a particular donor is 
positive or reactive, so long as this information is contained in the summary of 
records. 
 
2.  Examples of viable, leukocyte-rich cells or tissue include, but are not limited 
to:  
 
  Hematopoietic stem/progenitor cells 
  Semen 
 
You should consider cells and tissues to be viable and leukocyte-rich based on 
their status at the time of recovery, even if later processing might remove 
leukocytes.   
 
3.  Examples of cells or tissue that are not considered viable, leukocyte-rich cells 
or tissues include, but are not limited to:  
 
  Corneas 
  Sclera 
  Skin  
  Heart valves  
  Dura mater  
  Bone 
  Tendons  
  Ligaments 
  Cartilage 
  Oocytes 
 
Under  1271.45(b), in the case of embryos or cells derived from an embryo, a donor 
eligibility determination is required for both the oocyte donor and the semen donor.  
Therefore, although an embryo might not be considered leukocyte-rich, when an embryo 
is transferred to an individual who is not a sexually intimate partner, the semen donor 
should be tested for HTLV types I and II and for CMV. 
35 
  Contains Nonbinding Recommendations 
 
 
C.  How do I assess a donor of dura mater for TSE? 
 
You must perform an adequate assessment for donors of dura mater to detect evidence of 
TSE ( 1271.85(e)).  After the dura mater has been removed, you should have a qualified 
pathologist perform an examination of the donors brain.  Following fresh examination, 
the brain should be fixed and sliced, gross examination of the entire brain should be 
conducted (including multiple cross sections), and multiple specimens of tissue should be 
obtained (from different parts of the brain) for histological examination.  Exclude 
potential donors when any possible evidence of TSE-related changes is observed on 
histological examination.  There are currently no FDA-licensed, approved, or cleared 
donor screening tests for prions. 
 
 
VII.  ADDITIONAL SCREENING AND TESTING REQUIREMENTS FOR DONORS 
OF REPRODUCTIVE CELLS AND TISSUES ( 1271.75, 1271.80, AND 1271.85) 
   
A.  Do I need to screen and test all donors of reproductive cells and tissue?   
   
Except as provided in  1271.90, you must screen and test all directed reproductive 
donors (as defined in  1271.3(l)) and anonymous donors of reproductive cells and 
tissues ( 1271.75, 1271.80, and 1271.85) (Refs. 102 through 138).   
 
B.  What additional screening must I do for donors of reproductive cells and tissue?   
 
In addition to the screening required for all cell and tissue donors and, if applicable, the 
screening requirements for viable, leukocyte-rich cell and tissue donors, you must review 
the relevant medical records of donors of reproductive HCT/Ps (who are not sexually 
intimate partners) for risk factors for and clinical evidence of infection due to relevant 
sexually transmitted and genitourinary diseases that can be transmitted with the recovery 
of the reproductive cells or tissue ( 1271.75(c)).  These include: 
 
  Chlamydia trachomatis; and 
  Neisseria gonorrhea. 
 
Specific donor screening recommendations are described in section IV. of this document. 
 
C.  What additional testing must I perform on donors of reproductive cells and 
tissue?  
 
In addition to the testing required for all cell and tissue donors, and, if applicable, the 
testing required for donors of viable, leukocyte-rich cells and tissues, you must test 
donors of reproductive HCT/Ps (who are not sexually intimate partners) for evidence of 
infection due to relevant genitourinary disease agents ( 1271.85(c)).  These include: 
 
36 
  Contains Nonbinding Recommendations 
 
  Chlamydia trachomatis; and 
  Neisseria gonorrhea. 
 
Special note on Chlamydia trachomatis and Neisseria gonorrhea testing:  Although there 
are diagnostic tests available, there are currently no FDA-licensed, approved, or cleared 
tests for donor screening.  In the absence of such screening tests, you must use an FDA-
licensed, approved, or cleared diagnostic test labeled for the detection of these organisms 
in an asymptomatic, low-prevalence population ( 1271.80(c)).  FDA recommends 
Chlamydia trachomatis and Neisseria gonorrhea test kits utilizing NAT technology to 
adequately and appropriately reduce the risk of infectious disease transmission (Refs. 81, 
139 through 148).  You can find a listing of FDA-licensed or approved test kits for 
Chlamydia trachomatis and Neisseria gonorrhea at the following website:  
http://www.fda.gov/cber/tissue/prod.htm.   
 
Exception from testing requirement: 
 
If the reproductive cells or tissue are recovered by a method that ensures freedom from 
contamination of the cells or tissue by infectious disease organisms that may be present in 
the genitourinary tract, then tests for Chlamydia trachomatis and Neisseria gonorrhea are 
not required ( 1271.85(c)).  However, if these tests are performed and one or both results 
are reactive, the donor must be determined ineligible, regardless of the recovery method 
used ( 1271.80(d)(1)). 
 
D.  What follow-up testing is required for anonymous semen donors? 
 
At least 6 months after the donation, you must collect a new specimen from the 
anonymous semen donor and repeat testing required under  1271.85(a) through (c) ( 
1271.85(d)).  You must quarantine the donated semen until the retesting is complete and 
the donor is determined to be eligible ( 1271.60(a)).  See IV. D. for a discussion of 
screening of repeat donors. 
 
Note:  If a repeat anonymous semen donor discontinues donations, you should wait at 
least 6 months from the final donation and re-test the donor for all RCDADs in order to 
qualify the final donation, except that you may use the results of tests for Chlamydia 
trachomatis and Neisseria gonorrhea obtained at the final donation, or any time later than 
that, as the test of record to qualify that final donation.    
 
Example:  A donor tests negative or nonreactive for HBsAg and Hepatitis B core 
antibody.  He is retested 6 months later, and is still negative or nonreactive for HBsAg, 
but is positive or reactive for Hepatitis B core antibody.  The donor is ineligible.  The 
semen in quarantine should not be transferred to an anonymous recipient. 
 
37 
  Contains Nonbinding Recommendations 
 
E.  Is follow-up testing required for directed donors of semen? 
 
No, we do not require follow-up testing when semen is donated for directed use.  
Specimens collected for use in donor eligibility testing must be collected within 7 days of 
each collection ( 1271.80(b)).  You may alternately elect to perform quarantine of 
semen and retesting of the directed donor as described for anonymous semen donors in 
section VII.D. of this document ( 1271.85(d)), rather than performing donor testing 
within 7 days of each collection.  
 
F.  Is a donor eligibility determination required for gestational carriers or surrogate 
carriers? 
 
No.  Gestational or surrogate carriers are not considered to be donors according to the 
FDA definition of a donor ( 1271.3(m)).  Gestational or surrogate carriers are 
considered to be HCT/P recipients.    
 
G. Is a donor eligibility determination required for donors of reproductive cells and 
tissues that are transferred to gestational or surrogate carriers? 
 
Section 1271.45(b) states that in the case of an embryo or cells derived from an embryo, a 
donor eligibility determination is required for both the oocyte donor and the semen donor.  
In complying with screening and testing requirements when embryos are involved, you 
should consider the relationship between the gestational carrier and the oocyte and semen 
donors separately in order to determine which donor eligibility requirements apply.  
 
The following examples assume that when the embryos were formed, they were intended 
for transfer to a gestational carrier. 
 
Example:  A gestational carrier known to a couple will carry an embryo formed from the 
womans oocyte and a mixture of semen from the man and an anonymous donor.  The 
embryo(s) were formed to be carried for the couple by the gestational carrier.   
 
  No donor eligibility determination is required for the gestational carrier. 
  The couple is known to the recipient (the gestational carrier) so both members of 
the couple are considered directed donors ( 1271.3(l)). 
  A donor eligibility determination must be made for both members of that couple 
( 1271.45(b)), but the use of reproductive cells or tissue from an ineligible 
directed donor is not prohibited (with proper labeling) ( 1271.65 (b)). 
  Neither quarantine of the directed donors semen nor retesting of the directed 
donor is required ( 1271.60(a) and 1271.85(d)). 
  The other semen donor is not known to the gestational carrier, so that donor is 
considered an anonymous donor and must have a donor eligibility determination 
( 1271.3(l)).  If the semen donor is ineligible, the semen may not be used ( 
1271.45(b)). 
  Quarantine of the anonymous donors semen and retesting of the anonymous 
semen donor is required ( 1271.60(a) and 1271.85(d)). 
38 
  Contains Nonbinding Recommendations 
 
 
Example:  A gestational carrier known to a couple will carry an embryo formed from an 
oocyte donated by a donor who is known to the couple, but not to the gestational carrier, 
and semen from a member of that couple.  The embryo(s) were formed to be carried for 
the couple by the gestational carrier.    
 
  No donor eligibility determination is required for the gestational carrier. 
  The couple is known to the recipient (the gestational carrier) so the semen donor 
in this situation would be a directed donor ( 1271.3(l)). 
  A donor eligibility determination must be made for the directed semen donor each 
time he donates semen, but the use of semen from an ineligible directed donor is 
not prohibited (with proper labeling) ( 1271.65(b)). 
  Neither quarantine of the directed donors semen nor retesting of the directed 
donor is required ( 1271.60(a) and 1271.85(d)). 
  The oocyte donor is known to the couple but not known to the gestational carrier, 
so the donor is considered an anonymous donor ( 1271.3(l)).   
  The oocyte donor must have a donor eligibility determination ( 1271.45(b)).  If 
the oocyte donor is ineligible, the oocytes may not be used ( 1271.45(c)). 
 
Example:  A surrogate carrier is known to a couple.  The surrogates oocyte(s) and semen 
from a member of that couple will be used to form embryo(s) that will be carried for the 
couple by the surrogate. 
 
  No donor eligibility determination is required for the surrogate. 
  The couple is known to the surrogate, so the semen donor would be a directed 
donor ( 1271.3(l)). 
  A donor eligibility determination is required for the semen donor each time he 
donates semen ( 1271.45(b)), but the use of semen from an ineligible directed 
donor is not prohibited (with proper labeling) ( 1271.65(b)).  
  Neither quarantine of the directed donors semen nor retesting of the directed 
donor is required ( 1271.60(a) and 1271.85(d)). 
 
 
VIII.  EXCEPTIONS FROM THE REQUIREMENTS FOR DETERMINING DONOR 
ELIGIBILITY AND SPECIAL CIRCUMSTANCES ( 1271.90, 1271.60(d), 
1271.65(b), AND 1271.65(c)) 
 
This section describes:  (1) situations when you are not required to perform a donor-eligibility 
determination; (2) situations in which the donor-eligibility determination is incomplete; and (3) 
situations in which the use of cells or tissue from a donor who has been determined to be 
ineligible is not prohibited.  These situations require special labels.  We define the term label 
when used in this guidance and in  1271.60(d), 1271.65(b), and 1271.90(b), to mean either (1) 
a printed label affixed to the HCT/P container, or (2) a printed label affixed as a tie-tag to the 
HCT/P container.  However, if it is not physically possible to comply with (1) or (2), either 
because the container is too small to affix all of these labels to the container, or because the 
39 
  Contains Nonbinding Recommendations 
 
container is frozen, and therefore affixing the labels or attaching a tie-tag is not feasible, then the 
Warning statements in sections VIII.B.3., 5., and 6. of this document may accompany the 
HCT/P. 
 
A.  When is a donor eligibility determination not required?  ( 1271.90) 
 
There are five situations in which you are not required to make a determination of donor 
eligibility or to perform donor screening and testing ( 1271.90(a) and  1271.15(a)).  
You must apply special label requirements if you do not screen and test ( 1271.90(b)). 
 
Donor eligibility determinations are not required ( 1271.90(a) (1) through (4)) for: 
 
1.  Cells and tissue for autologous use ( 1271.90(a)(1));  
 
2.  Reproductive cells or tissue donated by a sexually intimate partner of the 
recipient for reproductive use ( 1271.90(a)(2);  
 
3.  Cryopreserved cells or tissue for reproductive use, other than embryos, 
exempt at the time of donation as described in 1 and 2, above, that are 
subsequently intended for directed donation, provided that 
 
a.  additional donations of suitable cells and tissues are unavailable due to the 
infertility or health condition of a donor of the cryopreserved reproductive 
cells or tissue; and 
 
b.  appropriate measures (see note after section VIII.A.4. of this document) 
are taken to screen and test the donor(s) before transfer to the recipient ( 
1271.90(a)(3)).  
 
This exception addresses the situation where the donor was not screened and tested at 
the time of cryopreservation of the reproductive cells or tissue, and where the donor 
cannot make additional donations (e.g., the woman is post-menopausal or has had her 
ovaries or uterus removed, or because the man has undergone chemotherapy which 
renders him infertile).  The donor wishes to make a directed donation of the 
cryopreserved semen or oocytes to someone the donor knows.  Under these 
circumstances, you should screen and test the donor at least six months after recovery 
of the cryopreserved HCT/Ps and before the donation is made.  In such cases, as in 
other cases involving directed donations of reproductive tissue, we would not prohibit 
the use of an HCT/P from an ineligible directed donor (section VIII.D.2. of this 
document).   
 
40 
  Contains Nonbinding Recommendations 
 
4.  A cryopreserved embryo, originally excepted under  1271.90(a)(2) at the 
time of cryopreservation, that is subsequently intended for directed or anonymous 
donation.  When possible, you should take appropriate measures (see note after 
section VIII.A.4. of this document) to screen and test the semen and oocyte 
donors before transfer of the embryo to the recipient ( 1271.90(a)(4)).   
 
This exception addresses the situation where sexually intimate partners were not 
screened and tested at the time of cyropreservation of their embryos, and later wish to 
make a directed or anonymous donation of their cryopreserved embryo(s).  Under 
these circumstances, you should cryopreserve the embryos for at least 6 months and 
when the decision is made to donate the embryo(s) to an individual or a gestational 
carrier, you should screen and test the semen and oocyte donors when possible.  In 
such cases, as in other cases involving directed donations of reproductive tissue 
(section VIII.D.2. of this document), the use of embryos from an ineligible directed 
donor is not prohibited.  In addition, although FDA requires appropriate screening 
and testing when possible, if appropriate screening and testing are not possible (e.g., 
because one of the donors is unavailable), you may still transfer the embryo into a 
recipient. Labeling requirements apply, regardless of whether the semen and oocyte 
donors were screened and tested (those labeling requirements are described in section 
VIII.B. of this document).   
 
Because one of the gamete donors would already have been found eligible, FDA also 
intends to apply this policy to a sexually intimate couples cryopreserved embryos 
where one of the gametes is from a qualified (i.e., eligible) third party gamete donor, 
and the other gamete is from the sexually intimate partner of the intended recipient.  
In this circumstance, you should also screen and test the sexually intimate partner 
gamete donor when possible, and labeling requirements would apply.   
 
Note:  By appropriate measures, we mean that you screen and test the donor(s) for 
those communicable disease agents for which a donor of such reproductive cells or 
tissue would ordinarily be tested at the time of donation, and a donor eligibility 
determination be made, except that the donor(s) do not have to be tested for 
Chlamydia trachomatis or Neisseria gonorrhea.  The reason is that testing for 
Chlamydia trachomatis or Neisseria gonorrhea at the time of donation of the 
reproductive cells or tissue would not provide information about the status of the 
donor(s) for these agents at the time of the earlier cryopreservation.   
 
To meet the donor testing requirements described in section VIII.A.3. or 
recommendations described in section VIII.A.4., if the donor(s) cannot be tested due 
to death or inability to locate the donor, you should use the most recent available 
specimen from the donor(s) to perform the appropriate testing.   
 
41 
  Contains Nonbinding Recommendations 
 
To meet the donor screening requirements described in section VIII.A.3. or 
recommendations described in section VIII.A.4., if the donor(s) cannot be 
interviewed in person due to death or inability to locate the donor(s), then the donor 
medical history interview may be performed with another individual as described in  
1271.3(n), and section IV.C. of this document. 
 
5.  In accordance with  1271.15(a), you are not required to make a determination 
of donor eligibility or to perform donor screening and testing if you are an 
establishment that uses HCT/Ps solely for nonclinical scientific or educational 
purposes (see section VIII.E. for those labeling requirements).  The  1271.90 
labeling requirements do not apply. 
 
B.  What special labeling is required for HCT/Ps that are excepted under the 
provision of  1271.90(a) from the donor eligibility determination ( 
1271.90(b)(1)through (6))?   
 
Note:  More than one of the following label requirements may apply to a particular 
HCT/P. 
 
1.  For HCT/Ps excepted under  1271.90(a)(1), if the HCT/Ps are stored for 
autologous use, then under  1271.90(b)(1) you must label the HCT/Ps FOR 
AUTOLOGOUS USE ONLY. 
 
2.  For HCT/Ps excepted under  1271.90(a)(1 through 4), if you do not test and 
screen a donor, then under  1271.90(b)(2) you must label the HCT/Ps from that 
donor NOT EVALUATED FOR INFECTIOUS SUBSTANCES unless you 
have performed all otherwise applicable screening and testing under  1271.75, 
1271.80, and 1271.85.   For instance, if you perform some but not all of the 
testing and screening that would otherwise be required in these sections, or if you 
do not use a registered, CLIA-certified laboratory, or FDA licensed, cleared, or 
approved donor screening tests, this label would apply.  This label would not 
apply to reproductive cells and tissue labeled in accordance with  1271.90(b)(6).   
 
Example 1:  You must label an HCT/P from an autologous donor who has not been 
screened and tested under the exception in  1271.90(a)(1), FOR AUTOLOGOUS 
USE ONLY and NOT EVALUATED FOR INFECTIOUS SUBSTANCES. 
 
Example 2:  A man wishes to donate his stored semen to his sexually intimate partner.  
You test the man for HIV-1 and HIV-2 before he donates the semen to his sexually 
intimate partner, but under the  1271.90 (a)(2) exception you are not required to test 
for any of the other relevant communicable diseases for which anonymous or directed 
sperm donors would be required to be tested.  If you do not perform all of the 
additional testing, you must label the stored semen NOT EVALUATED FOR 
INFECTIOUS SUBSTANCES. 
 
42 
  Contains Nonbinding Recommendations 
 
3.  For HCT/Ps excepted under  1271.90(a)(2 through 4), (excluding HCT/Ps for 
autologous use), you must under  1271.90(b)(3) label the HCT/P with 
WARNING:  Advise recipient of communicable disease risks when either the 
donor eligibility determination has not been completed or if screening or testing 
indicates the presence of relevant communicable disease agents and/or risk factors 
for or clinical evidence of relevant communicable disease agents or diseases. 
 
4.  For HCT/Ps excepted under  1271.90(a), if donor screening or testing 
indicates the presence of relevant communicable disease agents or diseases and/or 
risk factors for or clinical evidence of relevant communicable disease agents or 
diseases, then under 1271.90(b)(4) you must label the HCT/P with the Biohazard 
legend shown in  1271.3(h).   
 
5.  If HCT/Ps are recovered under  1271.90(a) from donors who have positive or 
reactive test results for any relevant communicable disease agent or disease, then 
under  1271.90(b)(5) you must label the HCT/P with WARNING:  Reactive 
test results for (name of disease agent or disease). 
 
6.  If reproductive tissue will be donated to a directed recipient under  
1271.90(a)(3) or a directed or anonymous recipient under  1271.90(a)(4), and the 
screening and testing is performed before transfer to the recipient rather than at 
the time of recovery, then under  1271.90(b)(6) you must label the HCT/P, 
Advise recipient that screening and testing of the donors were not performed at 
the time of cryopreservation of the reproductive cells or tissue, but have been 
performed subsequently.  Before transfer, if you have not performed all 
otherwise applicable screening and testing under  1271.75, 1271.80, and 
1271.85, then  1271.90(b)(2) would apply. 
 
Example:  HCT/Ps from a sexually intimate couple are used to form embryos.  The 
partners were not required to be screened and tested ( 1271.90(a)(2)).  Some 
embryos are transferred to the female partner and other embryos are cryopreserved.  It 
is determined that the female partner cannot carry a fetus to term.  The couple then 
decides to transfer the cryopreserved embryos to a gestational carrier who is known to 
the couple. 
 
  No donor eligibility determination is required for the gestational carrier. 
  The couple agrees to be screened and tested now, in accordance with  1271.75, 
1271.80, and 1271.85, except that the donor(s) do not have to be tested for 
Chlamydia trachomatis or Neisseria gonorrhea (See note in section VIII. A. of 
this document).  They are both determined to be eligible.   
  Under  1271.90(b)(6), you must prominently label the HCT/P with the 
statement: Advise recipient that screening and testing of the donors were not 
performed at the time of cryopreservation of the reproductive cells or tissue, but 
have been performed subsequently. 
  The cryopreserved embryos are transferred to the gestational carrier. 
43 
  Contains Nonbinding Recommendations 
 
  Note that if it was not possible to take appropriate measures to screen and test the 
donors (e.g., because one donor resides outside the United States and is 
unavailable) the embryos could nevertheless be transferred to the gestational 
carrier.  In that case, the labeling would contain the statements: Not evaluated for 
infectious substances ( 1271.90(b)(2)) and Warning: Advise recipient of 
communicable disease risk ( 1271.90(b)(3)). 
 
The records required under section  1271.55 (see section III.G. of this document), 
including the distinct identification code affixed to the HCT/P container, the 
statement of donor eligibility or ineligibility, based on the results of the screening and 
testing, and the summary of records are NOT required for HCT/Ps excepted under  
1271.90(a).  The reason is that  1271.55 applies only after a donor eligibility 
determination is complete, and this does not occur in the situations in  1271.90.  
However, you should include this information, if known.   
 
C.  Can cells or tissue from a donor be used before the donor eligibility 
determination under  1271.50 (a) is completed?   
 
Yes.  The use of cells or tissues from a donor before the donor eligibility determination is 
completed, is not prohibited under  1271.60(d) if there is a documented urgent medical 
need.  However, you must comply with the following requirements under  1271.60(d)(2) 
through (4).  
 
1.  If an HCT/P is made available based on a physicians request for urgent 
medical need before completing the donor-eligibility determination, you must 
document the urgent medical need and label the HCT/P prominently:  NOT 
EVALUATED FOR INFECTIOUS SUBSTANCES, and WARNING:  Advise 
patient of communicable disease risk.  
 
2.  The HCT/P must be accompanied by a statement of:  (a) the results of any 
required donor screening that has been completed; (b) the results of any required 
testing that has been completed; and (c) a list of any required screening and 
testing that has not yet been completed.  
 
3.  The manufacturer of the HCT/P must document that the physician using the 
HCT/P was notified that the testing and screening were not complete.  
 
4.  You must complete the donor-eligibility determination during or after the 
emergency use of the HCT/P, and inform the physician of the results of the 
determination.   
 
44 
  Contains Nonbinding Recommendations 
 
D.  Can cells or tissue from an ineligible donor ever be used for implantation, 
transplantation, infusion, or transfer? ( 1271.65(b)) 
 
Yes.  Under  1271.65(b), an HCT/P from an ineligible donor, based on required testing 
and/or screening results, is not prohibited from use for implantation, transplantation, or 
transfer in the following three circumstances. 
 
1.  The HCT/P is for allogeneic use in a first-degree or second-degree blood 
relative.  (Parents, children, and siblings are considered first-degree relatives.  
Aunts, uncles, nieces, nephews, first cousins, grandparents, and grandchildren are 
second-degree relatives.  Relations by adoption or marriage are not included); 
 
2.  The HCT/P consists of reproductive cells or tissue from a directed 
reproductive donor.  (A directed reproductive donor means a donor of 
reproductive cells or tissue, including semen, oocytes, and embryos, to which the 
donor contributed the spermatozoa or oocyte, to a specific recipient, and who 
knows and is known by the recipient before donation.  The term does not include 
a sexually intimate partner ( 1271.3(l)); or 
 
3.  There is an urgent medical need for the HCT/P based upon a physicians 
request documented by the establishment.  (An urgent medical need means that no 
comparable HCT/P is available and the recipient is likely to suffer death or 
serious morbidity without the HCT/P ( 1271.3(u)).   
 
An HCT/P made available under these provisions from an otherwise ineligible donor 
must be labeled prominently with the Biohazard legend ( 1271.3(h)) and with the 
statement WARNING:  Advise patient of communicable disease risk, and, in the case 
of reactive or positive test results, WARNING:  Reactive test results for (name of 
disease agent or disease) ( 1271.65(b)(2)).  The records required under  1271.55 must 
accompany the HCT/Ps used under  1271.65(b).  The records required under  1271.55 
(section III.G. of this document) include the distinct identification code affixed to the 
HCT/P container, the statement of donor eligibility or ineligibility, and the summary of 
records.  If the donor was determined to be ineligible based on screening, the summary of 
records must contain a statement noting the reason or reasons for the determination of 
ineligibility ( 1271.55(b)(4)). 
 
Moreover, if you are the manufacturer of an HCT/P used in the previously described 
circumstances, you must document that you notified the physician using the HCT/P of the 
results of screening and testing ( 1271.65(b)(3)).  
 
Note: If testing and screening are not required under the regulations, such as when a 
donor donates reproductive tissue to a sexually intimate partner, then the reproductive 
tissue may be donated in accordance with that exception, even if you know that the donor 
is otherwise ineligible.   
 
45 
  Contains Nonbinding Recommendations 
 
E.  Are there any other uses for HCT/Ps from donors determined to be ineligible? 
 
Yes.  The use of HCT/Ps from a donor determined to be ineligible, is not prohibited for 
nonclinical uses, so long as they bear the Biohazard legend and are labeled For 
Nonclinical Use Only ( 1271.65(c)). 
 
 
IX.  IMPLEMENTATION 
 
We recommend that you implement the recommendations in this guidance as soon as feasible, 
but not later than 6 months after the original issuance date of this guidance (February 27, 2007).  
 
 
X.  REFERENCES 
 
1.  Food and Drug Administration, Eligibility Determination for Donors of Human Cells, 
Tissues, and Cellular and Tissue-Based Products, Final Rule; 69 FR 29786.  
http://www.fda.gov/cber/rules/suitdonor.htm.   
2.  Food and Drug Administration, Guidance for Industry:  Screening and Testing of Donors 
of Human Tissue Intended for Transplantation, dated July 1997.  
http://www.fda.gov/cber/guidelines.htm.     
3.  Food and Drug Administration, Draft Guidance for Industry:  Eligibility Determination 
for Donors of Human Cells, Tissues, and Cellular and Tissue-based Products (HCT/Ps), 
dated May 2004.  http://www.fda.gov/cber/gdlns/tissdonor.htm. 
4.  Food and Drug Administration, Draft Guidance for Industry:  Preventive Measures to 
Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and 
Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular and 
Tissue-Based Products (HCT/Ps), dated June 2002.  
http://www.fda.gov/cber/guidelines.htm.   
5.  Food and Drug Administration, Draft Guidance for Industry:  Assessing Donor 
Suitability and Blood and Blood Product Safety in Cases of Known or Suspected West 
Nile Virus Infection dated April 2005.  http://www.fda.gov/cber/guidelines.htm.    
6.  Food and Drug Administration, Guidance for Industry: Recommendations for the 
Assessment of Donor Suitability and Blood and Blood Product Safety in Cases of Known 
or Suspected West Nile Virus Infection, dated June 2005.   
http://www.fda.gov/cber/guidelines.htm.  
7.  Food and Drug Aministration's Current Thinking on Donor Deferral for Potential or 
Documented Infection With West Nile Virus. Blood Products Advisory Committee 
(BPAC) Meeting, Holiday Inn Gaithersburg, October 22 2004.    
http://www.fda.gov/ohrms/dockets/ac/cber04.html#BloodProducts. 
8.  Fenner, I., et al., Smallpox and its eradication:  World Health Organization, 1988.   
9.  Blattner, R.J., et al., Antibody Response to Cutaneous Inoculation with Vaccinia Virus:  
Viremia and Viruria in Vaccinated Children.  J Pediatr 1964; 64:839-52.  
46 
  Contains Nonbinding Recommendations 
 
 
10.  Kempe C.H., Studies Smallpox and Complications of Smallpox Vaccination.  Pediatrics 
1960; 26:176-89.   
11.  Centers for Disease Control and Prevention.  Smallpox Vaccine (Vaccine Information 
Sheet) - Version II.  2003.  
http://www.bt.cdc.gov/agent/smallpox/vaccination/pdf/smallpox-vis.pdf. 
12.  Food and Drug Administration.  Guidance for Industry:  Recommendations for Deferral 
of Donors and Quarantine and Retrieval of Blood and Blood Products in Recent 
Recipients of Smallpox Vaccine (Vaccinia Virus) and Certain Contacts of Smallpox 
Vaccine Recipients, dated December 2002.  http://www.fda.gov/cber/guidelines.htm.     
13.  Centers for Disease Control and Prevention.  In the Absence of SARS-CoV Transmission 
Worldwide:  Guidance for Surveillance, Clinical and Laboratory Evaluation, and 
Reporting (Version 2).  January 21 2004.  
http://www.cdc.gov/ncidod/sars/pdf/absenceofsars.pdf.    
14.  Centers for Disease Control and Prevention.  Revised U.S. Surveillance Case Definition 
for Severe Acute Respiratory Syndrome (SARS) and Update on SARS Cases --- United 
States and Worldwide, December 2003.  Morbidity and Mortality Weekly Report 2003; 
52(49):1202-1206.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5249a2.htm.   
15.  Centers for Disease Control and Prevention.  Update: Severe Acute Respiratory 
Syndrome --- Worldwide and United States, 2003.  Morbidity and Mortality Weekly 
Report 2003; 52(28):664-665.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5228a4.htm.   
16.  Peiris, J.S., et al., The Severe Acute Respiratory Syndrome.  N Engl J Med 2003; 
349:2431-41. 
17.  Human Cells, Tissues and Cellular and Tissue-Based Products: Risk Factors for Semen 
Donation, Blood Products Advisory Committee (BPAC) Meeting, Hilton Silver Spring 
Hotel, 14 December 2001.  
http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3817t2.doc.    
18.  Public Health Service.  PHS Guideline for Preventing Transmission of HIV Through 
Transplantation of Human Tissue and Organs.  Morbidity and Mortality Weekly Report 
1994; 43(RR8):1-17.  http://www.cdc.gov/mmwr/PDF/RR/RR4308.pdf. 
19.  Buchbinder, S.P., et al., Feasibility of Human Immunodeficiency Virus Vaccine Trials in 
Homosexual Men in The United States: Risk Behavior, Seroincidence, And Willingness 
to Participate.  J Infect Dis 1996; 174:954-61.   
20.  Busch, M.P., et al., Estimation of HIV Incidence in U.S. Blood Donors Using A Novel 
Detuned Anti-Hiv Eia Test Strategy, 5th Conf Retrovir Oppor Infect 1998; abstract no. 
531.   
21.  Centers for Disease Control and Prevention.  Guidelines for National Human 
Immunodeficiency Virus Case Surveillance, Including Monitoring for Human 
Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome.  MMWR 
Recomm Rep 1999; 48(RR13):1-31.   
22.  Coleman, P.J., et al., Incidence of Hepatitis B Virus Infection in the United States, 1976-
1994: Estimates from the National Health and Nutrition Examination Surveys. J Infect 
Dis 1998; 178:954-9. 
23.  Cowan, D.N., et al., The Incidence of HIV Infection Among Men in the United States 
Army Reserve Components, 1985-1991. AIDS 1994; 8:505-11. 
47 
  Contains Nonbinding Recommendations 
 
24.  Davis, S.F., et al., Trends in HIV Prevalence Among Childbearing Women in the United 
States, 1989-1994. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 19:158-64. 
25.  Glynn, S.A., et al., Demographic Characteristics, Unreported Risk Behaviors, and The 
Prevalence and Incidence Of Viral Infections: A Comparison of Apheresis and Whole-
Blood Donors.  The Retrovirus Epidemiology Donor Study.  Transfusion 1998; 38:350-8. 
26.  Hawkins, R.E., et al., Risk of Viral Hepatitis Among Military Personnel Assigned to US 
Navy Ships.  J Infect Dis 1992; 165:716-9. 
27.  Holmberg, S.D., The Estimated Prevalence and Incidence Of HIV In 96 Large Us 
Metropolitan Areas.  Am J Public Health 1996; 86:642-54. 
28.  Hyams, K.C., et al.  Geographic risk Factors for Viral Hepatitis and Cytomegalovirus 
Infection Among United States Armed Forces Blood Donors. Transfusion 1992;  
32:644-7. 
29.  Karon, J.M., et al., Prevalence of HIV Infection in the United States, 1984 to 1992.  Jama 
1996; 276:126-31. 
30.  Katz, M.H., et al., Continuing High Prevalence of HIV and Risk Behaviors Among 
Young Men Who Have Sex With Men: The Young Men's Survey in the San Francisco 
Bay Area in 1992 to 1993 and in 1994 to 1995.  J Acquir Immune Defic Syndr Hum 
Retrovirol 1998; 19:178-81. 
31.  Koblin, B.A., Taylor, P.E., Avrett, S., Stevens, C.E., The Feasibility of Hiv-1 Vaccine 
Efficacy Trials Among Gay/Bisexual Men In New York City: Project Achieve.  AIDS 
Community Health Initiative Enroute to the Vaccine Effort.  AIDS 1996; 10:1555-61. 
32.  McFarland, W., et al., Detection of Early HIV Infection and Estimation of Incidence 
Using A Sensitive/Less-Sensitive Enzyme Immunoassay Testing Strategy at Anonymous 
Counseling and Testing Sites in San Francisco.  J Acquir Immune Defic Syndr 1999; 
22:484-9. 
33.  McFarland, W., et al., Estimation of Human Immunodeficiency Virus (HIV) 
Seroincidence Among Repeat Anonymous Testers in San Francisco.  Am J Epidemiol 
1997; 146:662-4. 
34.  McQuillan, G.M., et al., H.S. Prevalence of Hepatitis B Virus Infection in the United 
States: the National Health and Nutrition Examination Surveys, 1976 through 1994.  Am 
J Public Health 1999; 89:14-8. 
35.  Parrish, E.M., et al., HIV Infection in Disadvantaged Out-Of-School Youth:  Prevalence 
for U.S. Job Corps Entrants, 1990 through 1996.  Clinical Laboratory Science 1995; 
8:350-353. 
36.  Peterman, T.A., et al., Decreasing Prevalence Hides a High HIV Incidence: Miami. AIDS 
1995; 9:965-70. 
37.  Renzullo, P.O., et al., Human Immunodeficiency Virus Type-1 Seroconversion Trends 
Among Young Adults Serving in the United States Army, 1985-1993.  United States 
Military Medical Consortium for Applied Retroviral Research.  J Acquir Immune Defic 
Syndr Hum Retrovirol 1995; 10:177-85. 
38.  Seage, G.H., et al., Feasibility of Conducting HIV-1 Vaccine Trials in the United States:  
Recruitment, Retention and HIV-1 Seroincidence From the HIV Network for Prevention 
Trials (HIVNET) Vaccine Preparedness Study (VPS).  12th World AIDS Conference, 
1998.
48 
  Contains Nonbinding Recommendations 
 
 
39.  Tabet, S.R., et al., Incidence of HIV and Sexually Transmitted Diseases (STD) in a 
Cohort of HIV-negative Men Who Have Sex With Men (MSM).  AIDS 1998; 12:2041-8. 
40.  Thomas, D.L., et al., Hepatitis C, Hepatitis B, and Human Immunodeficiency Virus 
Infections Among Non-Intravenous Drug-Using Patients Attending Clinics for Sexually 
Transmitted Diseases.  J Infect Dis 1994; 169:990-5. 
41.  Torian, L., et al., High HIV Seroincidence in Nonwhite Bisexual Men Making Repeat 
Visits to A New York City Sexually Transmitted Disease Clinic, 1994-1995:  Results of 
A Blinded Longitudinal Survey., 4th Conference on Retroviruses and Opportunistic 
Infections 1997, 1997. 
42.  Valdiserri, R.O., et al., Trends in HIV Seropositivity in Publicly Funded HIV Counseling 
and Testing Programs: Implications for Prevention Policy.  Am J Prev Med 1998; 14:31-
42. 
43.  Valleroy, L.A., et al., HIV Infection in Disadvantaged Out-Of-School Youth: Prevalence 
for U.S. Job Corps Entrants, 1990 through 1996.  J Acquir Immune Defic Syndr Hum 
Retrovirol 1998; 19:67-73. 
44.  Weinstock, H., et al., HIV Seroincidence and Risk Factors Among Patients Repeatedly 
Tested For HIV Attending Sexually Transmitted Disease Clinics in the United States, 
1991 to 1996. STD Clinic HIV Seroincidence Study Group.  J Acquir Immune Defic 
Syndr Hum Retrovirol 1998; 19:506-12. 
45.  Centers for Disease Control and Prevention.  HIV and AIDS - United States, 1981-2000. 
Morbidity and Mortality Weekly Report 2001; 50:430-4.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5021a2.htm.    
46.  Centers for Disease Control and Prevention.  HIV Prevalence Trends in Selected 
Populations in the United States:  Results from National Serosurveillance, 1993-1997.  
2001.  http://www.cdc.gov/hiv/pubs/hivprevalence/toc.htm.   
47.  Alter, M.J., et al., The Prevalence of Hepatitis C Virus Infection in the United States, 
1988 through 1994.  N Engl J Med 1999; 341:556-62. 
48.  Armstrong, G.L., et al., The Past Incidence of Hepatitis C Virus Infection:  Implications 
for the Future Burden of Chronic Liver Disease in the United States.  Hepatology 2000; 
31:777-82.   
49.  Centers for Disease Control and Prevention.  Recommendations for Prevention and 
Control of Hepatitis C Virus (HCV) Infection and HCV-related Chronic Disease. 
MMWR Recomm Rep 1998; 47:1-39.   
50.  Des Jarlais, D.C., et al., HIV Incidence Among Injection Drug Users in New York City, 
1992-1997: Evidence for a Declining Epidemic.  Am J Public Health 2000; 90:352-9.   
51.  Edlin, B.R., et al., High HIV Incidence Among Young Urban Street-Recruited Crack 
Cocaine Smokers, XI International Conference on AIDS, 1996. 
52.  Garfein, R.S., et al., Prevalence and Incidence of Hepatitis C Virus Infection Among 
Young Adult Injection Drug Users.  J Acquir Immune Defic Syndr Hum Retrovirol 1998; 
18 Suppl 1:S11-9. 
53.  Garfein, R.S., et al., Viral Infections in Short-Term Injection Drug Users: The Prevalence 
of The Hepatitis C, Hepatitis B, Human Immunodeficiency, and Human T-lymphotropic 
Viruses.  Am J Public Health 1996; 86:655-61.   
54.  Hagan, H., et al., Syringe Exchange and Risk af Infection With Hepatitis B and C 
Viruses.  Am J Epidemiol 1999; 149:203-13.   
49 
  Contains Nonbinding Recommendations 
 
55.  Kerndt, P.R., et al., HIV Incidence Among Injection Drug Users Enrolled in a Los 
Angeles Methadone Program.  Jama 1995; 273:1831-2.   
56.  Meyers, K., et al., Will Preventive HIV Vaccine Efficacy Trials Be Possible With Female 
Injection Drug Users?  J Acquir Immune Defic Syndr Hum Retrovirol 1995; 10:577-85.   
57.  Nelson, K.E., Temporal trends, demographic and behavioral risk factors for HIV 
incidence among injection drug users in Baltimore. Am J Epidemiol 1999; 149:S10.   
58.  Nelson, K.E., et al., Temporal Trends in the Incidence of Human Immunodeficiency 
Virus Infection and Risk Behavior Among Injection Drug Users in Baltimore, Maryland, 
1988-1998.  Am J Epidemiol 2002; 156:641-53.   
59.  Villano, S.A., et al., Incidence and Risk Factors for Hepatitis C Among Injection Drug 
Users in Baltimore, Maryland.  J Clin Microbiol 1997; 35:3274-7.   
60.  Schreiber, G.B., et al., The Risk of Transfusion-Transmitted Viral Infections.  The 
Retrovirus Epidemiology Donor Study.  N Engl J Med 1996; 334:1685-90.   
61.  Onorato, I.M., et al., Prevalence, Incidence, and Risks for HIV-1 Infection in Female Sex 
Workers in Miami, Florida.  J Acquir Immune Defic Syndr Hum Retrovirol 1995; 9:395-
400.   
62.  Rosenblum, L., et al., Sexual Practices in The Transmission Of Hepatitis B Virus and 
Prevalence of Hepatitis Delta Virus Infection in Female Prostitutes in the United States.  
Jama 1992; 267:2477-81.   
63.  Williams, C.M., Sexual Practices Associated With Hepatitis C Virus Infection Among 
Non Injecting-Drug-Using Female Prostitutes in the United States, 6th International 
Symposium on Hepatitis C & Related Viruses:  Molecular Virology and Pathogenesis, 
1999.   
64.  Public Health Service.  PHS Inter-Agency Guidelines for Screening Donors of Blood, 
Plasma, Organs, Tissues, and Semen for Evidence of Hepatitis B and Hepatitis C. 
Morbidity and Mortality Weekly Report 1991; 40:1-17.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/00043883.htm.   
65.  NIH Consensus Statement.  Management of Hepatitis C:  2002.  2002; 19:24.  
http://www.consensus.nih.gov/cons/116/116cdc_intro.htm.   
66.  Food and Drug Administration, Draft Guidance for Industry: Acceptable Full-Length 
Donor History Questionnaire and Accompanying Materials for Use in Screening Human 
Donors of Blood and Blood Componentsdated May 2004.  
http://www.fda.gov/cber/guidelines.htm.     
67.  Food and Drug Administration Memorandum to All Blood Establishments for "Deferral 
of Current and Recent Inmates of Correctional Institutions as Donors of Whole Blood, 
Blood Components, Source Leukocytes, and Source Plasma" June 8, 1995.  
http://www.fda.gov/cber/bldmem/060895.txt.    
68.  Ruiz, J.D., et al., Prevalence and Correlates of Hepatitis C Virus Infection Among 
Inmates Entering The California Correctional System.  West J Med 1999; 170:156-60. 
69.  Food and Drug Administration Revised Recommendations Memorandum to All Blood 
Establishments for "Testing Whole Blood, Blood Components, Source Plasma and 
Source Leukocytes for Antibody to Hepatitis C Virus Encoded Antigen (Anti-HCV)" 
April 23, 1992.  http://www.fda.gov/cber/memo.htm.  
50 
  Contains Nonbinding Recommendations 
 
70.  Food and Drug Administration Memorandum to All Blood Establishments for 
"Exemptions to Permit Persons with a History of Viral Hepatitis Before the Age of 
Eleven Years to Serve as Donors of Whole Blood and Plasma:  Alternative Procedures, 
21 CFR 640.120" April 23, 1992.  http://www.fda.gov/cber/bldmem/042392ex.txt.    
71.  Food and Drug Administration Recommendations to All Blood Establishments for 
"Donor Suitability Related to Laboratory Testing for Viral Hepatitis and a History of 
Viral Hepatitis" December 22, 1993.  http://www.fda.gov/cber/bldmem/122293.txt.    
72.   Centers for Disease Control and Prevention. Clinical Guidance on the Identification and 
Evaluation of Possible SARS-CoV Disease Among Persons Presenting with Community-
Acquired Illness (Version 2).  January 8, 2004.  http://www.fda.gov/cber/memo.htm.   
73.  Food and Drug Administration, Guidance for Industry:  Recommendations for the 
Assessment of Donor Suitability and Blood Product Safety in Cases of Suspected Severe 
Acute Respiratory Syndrome (SARS) or Exposure to SARS dated April 2003.  
http://www.fda.gov/cber/gdlns/sarsbldgd1.htm.   
74.  Food and Drug Administration, Guidance for Industry: Revised Recommendations for 
the Assessment of Donor Suitability and Blood Product Safety in Cases of Suspected 
Severe Acute Respiratory Syndrome (SARS) or Exposure to SARS dated September 
2003. http://www.fda.gov/cber/guidelines.htm.     
http://www.fda.gov/cber/blood/bldguid.htm 
75.  Food and Drug Administration, Guidance for Industry: Revised Preventive Measures to 
Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and 
Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products dated January 
2002. http://www.fda.gov/cber/guidelines.htm.     
76.  Food and Drug Administration Recommendations to all Blood Establishments for 
"Interim Recommendations for Deferral of Donors at Increased Risk for HIV-1 Group O 
Infection", December 11, 1996.  http://www.fda.gov/cber/bldmem/mem121196a.txt.     
77.  Food and Drug Administration, Draft Guidance for Industry:  Precautionary Measures to 
Reduce the Possible Risk of Transmission of Zoonoses by Blood and Blood Products 
from Xenotransplantation Product Recipients and Their Intimate Contacts, dated 
February 2002.  http://www.fda.gov/cber/gdlns/zoobldxeno.htm.   
78.  Report of the Food and Drug Administration Subcommittee on Xenotransplantation: 
meeting of January 13, 2000, Center for Biologics Evaluation and Research. 
Xenotransplantation 2000; 7:75-9.  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citati
on&list_uids=10961289.    
79.  Food and Drug Administration Revised Recommendations to all Blood Establishments 
for "The Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood 
and Blood Products", April 23, 1992.  http://www.fda.gov/cber/memo.htm.   
80.  Food and Drug Administration Recommendations to all Blood Establishments for 
"Clarification of FDA Recommendations for Donor Deferral and Product Distribution 
Based on the Results of Syphilis Testing", December 12, 1991.     
http://www.fda.gov/cber/memo.htm.   
 81.  Centers for Disease Control and Prevention.  Outbreak of Severe Acute Respiratory 
Syndrome ---Worldwide, 2003.  Morbidity and Mortality Weekly Report 2003; 
52(11):226-228.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5211a5.htm.  
51 
  Contains Nonbinding Recommendations 
 
 
82.  Centers for Disease Control and Prevention.  Updated Interim Surveillance Case 
Definition for Severe Acute Respiratory Syndrome (SARS)---April 29, 2003.  2003; 
52(17):391-393.  http://www.cdc.gov/ncidod/sars/casedefinition.htm. 
83.  Centers for Disease Control and Prevention.  Severe Acute Respiratory Syndrome;  
"Current SARS Situation".  http://www.cdc.gov/ncidod/sars/situation.htm.  
84.  Mandell: Principles and Practice of Infectious Diseases, 5th ed.: Churchill Livingstone, 
Inc., 2000:806-808; 1991-2000.   
85.  Food and Drug Administration Recommendations to all Blood Establishments for 
"HTLV-I Antibody Testing", November 29, 1988.  
http://www.fda.gov/cber/bldmem/112988.txt. 
86.  Food and Drug Administration, Guidance for Industry:  Donor Screening for Antibodies 
to HTLV-II, dated August 1997.  http://www.fda.gov/cber/guidelines.htm.  
87.  Centers for Disease Control and Prevention.  Smallpox Home Page.  Last modified date: 
April 4, 2005.  http://www.bt.cdc.gov/agent/smallpox/index.asp.   
88.  Chopek, M.M., Protein and Biochemical Changes During Plasma Exchange. Therapeutic 
Hemapheresis: A Technical Workshop Presented by the Committee on Technical 
Workshops, American Association of Blood Banks 1980; 1980:13-52.   
89.  Dudrick, S.J., Professor of Surgery, Yale University, 2005: Personal Communication. 
90.  Food and Drug Administration, Guidance for Industry:  Use of Nucleic Acid Tests on 
Pooled and Individual Samples from Donors of Whole Blood and Blood Components 
(including Source Plasma and Source Leukocytes) to Adequately and Appropriately 
Reduce the Risk of Transmission of HIV-1 and HCV dated October 2004.  
http://www.fda.gov/cber/guidelines.htm.     
91.  Food and Drug Administration Recommendations to all Blood Establishments 
Concerning "Testing for Antibody to Hepatitis B Core Antigen (Anti-HBc)", September 
10, 1991.  http://www.fda.gov/cber/bldmem/091091.txt.   
92.  Hsia, C.C., et al., Molecular and Serological Aspects of HBsAg-negative Hepatitis B 
Virus Infections in North America.  J Med Virol 2003; 70:20-6.   
93.  Minuk, G.Y., et al., Occult Hepatitis B Virus Infection in a North American Community-
Based Population.  J Hepatol 2005; 42:480-5.   
94.  Nakamoto, N., et al., Genomic Mutations With Amino Acid Substitutions of Circulating 
Hepatitis B Virus Found in Non-B, Non-C Patients With Hepatocellular Carcinoma.  
Intern Med 2003; 42:322-30.   
95.  Takaguchi, K., et al., Detection of Hepatitis B Virus DNA in the Liver and Serum of 
Patients With Hepatitis B Surface Antigen and Hepatitis C Virus Antibody Negative 
Chronic Liver Disease.  Hepatol Res 2002; 22:139-144.   
96.  Torbenson, M., et al., High Prevalence of Occult Hepatitis B in Baltimore Injection Drug 
Users.  Hepatology 2004; 39:51-7.   
97.  Weber, B., et al., Hepatitis B Virus Markers in Anti-HBc Only Positive Individuals.   
J Med Virol 2001; 64:312-9.   
98.  Fagan, E.A., et al., Persistence of Free HBV DNA in Body Secretions and Liver Despite 
Loss of Serum HBV DNA After Interferon-Induced Seroconversion.  J Med Virol 1986; 
20:183-8.   
99.  Zou, S., et al., Probability of Viremia with HBV, HCV, HIV, and HTLV Among Tissue 
Donors in the United States.  N Engl J Med 2004; 351:751-9.   
52 
  Contains Nonbinding Recommendations 
 
100.  Food and Drug Administration, Draft Guidance for Industry: Revised Recommendations 
for Donor and Product Management Based on Screening Tests for Syphilis, dated June 
2003.  http://www.fda.gov/cber/guidelines.htm.     
101.  Food and Drug Administration Recommendations to all Blood Establishments for "Donor 
Screening with a Licensed Test for HIV-1 Antigen", August 8, 1995.  
http://www.fda.gov/cber/bldmem/hiv-ag.txt. 
102.  Ali, B.A., et al., Detection and Expression of Hepatitis B Virus X Gene in One And Two-
Cell Embryos From Golden Hamster Oocytes in Vitro Fertilized with Human 
Spermatozoa Carrying HBV DNA.  Mol Reprod Dev 2005; 70:30-6.   
103.  Bertrand, E., et al., Presence of HIV-1 in Follicular Fluids, Flushes And Cumulus 
Oophorus Cells Of HIV-1-Seropositive Women During Assisted-Reproduction 
Technology.  AIDS 2004; 18:823-5. 
104.  Bourlet, T., et al., Multicenter Quality Control for the Detection of Hepatitis C Virus 
RNA In Seminal Plasma Specimens.  J Clin Microbiol 2003; 41:789-93. 
105.  Bujan, L., et al., Intermittent Human Immunodeficiency Type 1 Virus (HIV-1) Shedding 
in Semen and Efficiency of Sperm Processing Despite High Seminal HIV-1 RNA levels.  
Fertil Steril 2002; 78:1321-3. 
106.  Bujan, L., et al., Factors of Intermittent HIV-1 Excretion in Semen and Efficiency of 
Sperm Processing in Obtaining Spermatozoa Without HIV-1 Genomes.  AIDS 2004; 
18:757-66. 
107.  Bujan, L., et al., Insemination With Isolated and Virologically Tested Spermatozoa is a 
Safe Way For Human Immunodeficiency Type 1 Virus-Serodiscordant Couples With an 
Infected Male Partner to Have a Child.  Fertil Steril 2004; 82:857-62. 
108.  Cassuto, N.G., et al., A Modified RT-PCR Technique to Screen for Viral RNA in the 
Semen of Hepatitis C Virus-Positive Men.  Hum Reprod 2002; 17:3153-6. 
109.  Davison, F., et al., Detection of Hepatitis B Virus DNA in Spermatozoa, Urine, Saliva 
and Leucocytes, of Chronic HBsAg Carriers.  A Lack of Relationship with Serum 
Markers of Replication.  J Hepatol 1987; 4:37-44. 
110.  Dejucq, N., Jegou, B. Viruses in the Mammalian Male Genital Tract and Their Effects on 
the Reproductive System.  Microbiol Mol Biol Rev 2001; 65:208-31. 
111.  Devaux, A., et al., Hepatitis C Virus Detection in Follicular Fluid and Culture Media 
From HCV+ Women, And Viral Risk During IVF Procedures.  Hum Reprod 2003; 
18:2342-9. 
112.  Englert, Y., et al., Medically Assisted Reproduction in the Presence of Chronic Viral 
Diseases.  Hum Reprod Update 2004; 10:149-62. 
113.  Garrido, N., et al., Report of the Results of a 2 year Programme of Sperm Wash and ICSI 
Treatment for Human Immunodeficiency Virus and Hepatitis C Virus Serodiscordant 
Couples.  Hum Reprod 2004; 19:2581-6. 
114.  Gilling-Smith, C.. HIV Prevention.  Assisted Reproduction in HIV-Discordant Couples.  
AIDS Read 2000; 10:581-7. 
115.  Hadchouel, M., et al., Presence of HBV DNA in Spermatozoa:  A Possible Vertical 
Transmission of HBV via the Germ Line.  J Med Virol 1985; 16:61-6. 
116.  Hanabusa, H., et al., An Evaluation of Semen Processing Methods for Eliminating HIV-
1.  Aids 2000; 14:1611-6.
53 
  Contains Nonbinding Recommendations 
 
 
117.  Huang, J.M., et al., Effects of Hepatitis B Virus Infection on Human Sperm 
Chromosomes.  World J Gastroenterol 2003; 9:736-40. 
118.  Huang, J.M., et al., Studies on the Integration of Hepatitis B Virus DNA Sequence in 
Human Sperm Chromosomes.  Asian J Androl 2002; 4:209-12. 
119.  Leruez-Ville, M., et al., Assisted Reproduction in HIV-1-Serodifferent Couples:  The 
Need for Viral Validation of Processed Semen.  AIDS 2002; 16:2267-73. 
120.  Lesourd, F., et al., Transmissions of Hepatitis C Virus During the Ancillary Procedures 
for Assisted Conception.  Hum Reprod 2000; 15:1083-5. 
121.  Letur-Konirsch, H., et al., Safety of Cryopreservation Straws for Human Gametes Or 
Embryos:  A Study with Human Immunodeficiency Virus-1 Under Cryopreservation 
Conditions.  Hum Reprod 2003; 18:140-4. 
122.  Levy, R., et al., Pregnancy After Safe IVF With Hepatitis C Virus RNA-Positive Sperm.  
Hum Reprod 2002; 17:2650-3. 
123.  Levy, R., et al., Transmission Risk of Hepatitis C Virus in Assisted Reproductive 
Techniques.  Hum Reprod 2000; 15:810-6. 
124.  Maertens, A., et al., Validation of Safety Procedures for the Cryopreservation of Semen 
Contaminated With Hepatitis C Virus in Assisted Reproductive Technology.  Hum 
Reprod 2004; 19:1554-7. 
125.  Manno, M., et al., Preliminary Evidence on The Safety of ICSI with Testicular 
Spermatozoa in Hcv-Infected Male:  A Case Report.  Hum Reprod 2003; 18:1666-8. 
126.  Marina, S., et al., Human Immunodeficiency Virus Type 1--Serodiscordant Couples Can 
Bear Healthy Children After Undergoing Intrauterine Insemination.  Fertil Steril 1998; 
70:35-9. 
127.  Meseguer, M., et al., Comparison of Polymerase Chain Reaction-Dependent Methods for 
Determining The Presence of Human Immunodeficiency Virus and Hepatitis C Virus in 
Washed Sperm.  Fertil Steril 2002; 78:1199-202. 
128.  Nicopoullos, J.D., et al., The Effect of Human Immunodeficiency Virus on Sperm 
Parameters and the Outcome of Intrauterine Insemination Following Sperm Washing.  
Hum Reprod 2004; 19:2289-97. 
129.  Papaxanthos-Roche, A., et al., PCR-Detected Hepatitis C Virus RNA Associated with 
Human Zona-Intact Oocytes Collected From Infected Women for ART.  Hum Reprod 
2004; 19:1170-5. 
130.  Pasquier, C., et al., Intermittent Detection of Hepatitis C Virus (HCV) in Semen From 
Men With Human Immunodeficiency Virus Type 1 (HIV-1) and HCV.  J Med Virol 
2003; 69:344-9. 
131.  Passos, E.P., et al., Hepatitis C Virus Infection and Assisted Reproduction.  Hum Reprod 
2002; 17:2085-8. 
132.  Payne, M.A., Lamb, E.J., Use of Frozen Semen to Avoid Human Immunodeficiency 
Virus Type 1 Transmission by Donor Insemination:  A Cost-Effectiveness Analysis.  
Fertil Steril 2004; 81:80-92. 
133.  Politch, J.A., et al., Separation of Human Immunodeficiency Virus Type 1 From Motile 
Sperm By The Double Tube Gradient Method Versus Other Methods.  Fertil Steril 2004; 
81:440-7. 
134.  Semprini, A.E., et al., Insemination of HIV-Negative Women with Processed Semen of 
HIV-Positive Partners.  Lancet 1992; 340:1317-9. 
54 
  Contains Nonbinding Recommendations 
 
135.  Steyaert, S.R., et al., Infections in IVF:  Review and Guidelines.  Hum Reprod Update 
2000; 6:432-41. 
136.  Tedder, R.S., et al., Hepatitis B Transmission from Contaminated Cryopreservation Tank.  
Lancet 1995; 346:137-40. 
137.  Wang, S., et al., Identification of Hepatitis B Virus Vertical Transmission from Father to 
Fetus by Direct Sequencing.  Southeast Asian J Trop Med Public Health 2003; 34:106-
13. 
138.  Zhang, H., et al., Human Immunodeficiency Virus Type 1 in the Semen of Men 
Receiving Highly Active Antiretroviral Therapy.  N Engl J Med 1998; 339:1803-9. 
139.  Centers for Disease Control and Prevention.  Sexually Transmitted Diseases Treatment 
Guidelines.  MMWR Recomm Rep 2002; 51(RR06):1-80.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5106a1.htm.   
140.  Chacko, M.R., et al., Chlamydia and Gonorrhea Screening in Asymptomatic Young 
Women.  J Pediatr Adolesc Gynecol 2004; 17:169-78. 
141.  Dowell, S.F., et al., Standardizing Chlamydia Pneumoniae Assays: Recommendations 
from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre 
for Disease Control (Canada).  Clin Infect Dis 2001; 33:492-503. 
142.  Ford, C.A., et al., Testing for Chlamydial and Gonorrheal Infections Outside of Clinic 
Settings:  A Summary Of The Literature.  Sex Transm Dis 2004; 31:38-51. 
143.  Fredlund, H., et al., Molecular Genetic Methods for Diagnosis and Characterisation of 
Chlamydia Trachomatis and Neisseria Gonorrhoeae:  Impact On Epidemiological 
Surveillance And Interventions.  Apmis 2004; 112:771-84. 
144.  Rager, K.M., Biro, F.M., Techniques of Testing For Sexually Transmitted Diseases.  Curr 
Womens Health Rep 2001; 1:111-5. 
145.  Schneede, P., et al., Sexually Transmitted Diseases (STDs)--A Synoptic Overview for 
Urologists.  Eur Urol 2003; 44:1-7. 
146.  Wiesenfeld, H.C., et al., Self-Collection of Vaginal Swabs for the Detection of 
Chlamydia, Gonorrhea, and Trichomoniasis:  Opportunity to Encourage Sexually 
Transmitted Disease Testing Among Adolescents.  Sex Transm Dis 2001; 28:321-5. 
147.  Centers for Disease Control and Prevention.  Screening Tests to Detect Chlamydia 
Trachomatis and Neisseria Gonorrhoeae Infections--2002.  MMWR Recomm Rep 2002; 
51(RR15):1-38; quiz CE1-4.  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citati
on&list_uids=12418541.   
148.  Holland-Hall, C.M., et al., Self-Collected Vaginal Swabs for the Detection of Multiple 
Sexually Transmitted Infections in Adolescent Girls.  J Pediatr Adolesc Gynecol 2002; 
15:307-13.   
149.  Centers for Disease Control and Prevention.  Possible West Nile Virus Transmission to 
an Infant Through Breast-Feeding --- Michigan, 2002.  Morbidity and Mortality Weekly 
Report 2002; 51:877-888.  
http://www.cdc.gov/mmwr//preview/mmwrhtml/mm5139a1.htm.  
150.  Pealer, L.N., et al., Transmission of West Nile Virus Through Blood Transfusion in the 
United States in 2002.  N Engl J Med 2003; 349:1236-45. 
151.  Centers for Disease Control and Prevention.  Intrauterine West Nile Virus Infection --- 
New York, 2002.  Morbidity and Mortality Weekly Report 2002; 51:1136-1136. 
55 
  Contains Nonbinding Recommendations 
 
152.  Centers for Disease Control and Prevention.  Erratum: Vol. 52, No. 38. Morbidity and 
Mortality Weekly Report 2003; 52:942.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5239a8.htm.  
153.  Centers for Disease Control and Prevention.  Update: Detection of West Nile Virus in 
Blood Donations --- United States, 2003.  Morbidity and Mortality Weekly Report 2003; 
52:916-919.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5238a6.htm  
154.  Centers for Disease Control and Prevention. West Nile Virus Home.  Access date:  20 
April 2005.  Last Update Date:  11 January 2005. 
155.  Centers for Disease Control and Prevention. West Nile Virus Activity --- United States, 
November 3--8, 2004. Morbidity and Mortality Weekly Report 2004; 53:1050-1051.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5344a7.htm 
156.  Centers for Disease Control and Prevention. West Nile Virus Activity --- United States, 
November 9--16, 2004. Morbidity and Mortality Weekly Report 2004; 53:1071-1072.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a4.htm. 
157.  Martin, G.S., et al., The Epidemiology of Sepsis in the United States from 1979 through 
2000.  N Engl J Med 2003; 348:1546-54.  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citati
on&list_uids=12700374. 
158.  Centers for Disease Control and Prevention.  Septic Arthritis Following Anterior Cruciate 
Ligament Reconstruction Using Tendon Allografts---Florida And Louisiana, 2000.  
Morbidity and Mortality Weekly Report 2001; 50:1080-1083.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5048a3.htm.  
159.  Centers for Disease Control and Prevention.  Unexplained Deaths Following Knee 
Surgery---Minnesota, November 2001.  Morbidity and Mortality Weekly Report 2001; 
50:1035-1036.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5046a3.htm.   
160.  Centers for Disease Control and Prevention.  Update:  Allograft-Associated Bacterial 
Infections --- United States, 2002.  Morbidity and Mortality Weekly Report 2002; 
51:207.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5110a2.htm. 
161.  Centers for Disease Control and Prevention.  Update:  Unexplained deaths following 
knee surgery---Minnesota, 2001.  Morbidity and Mortality Weekly Report 2001; 
50:1080.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5048a2.htm  
162.  Eastlund, T., Infectious Disease Transmission Through Cell, Tissue, And Organ 
Transplantation: Reducing the Risk Through Donor Selection.  Cell Transplant 1995; 
4:455-77.   
163.  Brecher, M.E., Hay, S.N., Bacterial Contamination Of Blood Components.  Clin 
Microbiol Rev 2005; 18:195-204. 
164.  Centers for Disease Control and Prevention.  Fatal Bacterial Infections Associated with 
Platelet Transfusions --- United States, 2004.  Morbidity and Mortality Weekly Report 
2005; 54:168-170.  http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5407a2.htm.  
165.  Angus, D.C., et al., Epidemiology of Severe Sepsis in the United States:  Analysis of 
Incidence, Outcome, and Associated Costs of Care.  Crit Care Med 2001; 29:1303-10. 
166.  Annane, D., et al., Septic Shock.  Lancet 2005; 365:63-78. 
167.  McBean, M., Rajamani, S.  Increasing Rates of Hospitalization Due to Septicemia in the 
US Elderly Population, 1986-1997.  J Infect Dis 2001; 183:596-603.
56 
  Contains Nonbinding Recommendations 
 
 
168.  Sessler, C.N., Shepherd, W., New Concepts in Sepsis.  Curr Opin Crit Care 2002; 8:465-
72. 
169.  Angus, D.C., Wax, R.S., Epidemiology of Sepsis:  An Update. Crit Care Med 2001; 
29:S109-16. 
170.  Cono, J., et al., Smallpox Vaccination and Adverse Reactions.  Guidance for clinicians. 
MMWR Recomm Rep 2003; 52:1-28.   
171.  Lupatkin, H., et al., Smallpox in the 21st century.  Anesthesiol Clin North America 2004; 
22:541-61, viii.   
172.  Sepkowitz, K.A., How Contagious Is Vaccinia?  N Engl J Med 2003; 348:439-46.   
173.  Centers for Disease Control and Prevention.  Vaccinia (Smallpox) Vaccine 
Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001.  
Morbidity and Mortality Weekly Report 2001; 50(RR10):1-25.  
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5010a1.htm.  
174.  Koplan, J.P., Marton, K.I., Smallpox vaccination revisited.  Some Observations on the 
Biology of Vaccinia.  Am J Trop Med Hyg 1975; 24:656-63.   
175.  Department of Defense Health Care Provider's Briefing, January 16, 2004.   
176.  Lorich, M.F., et al., Conjugal Transfer Vaccinia.  J Am Acad Dermatol 2004; 51:460-2.   
177.  Deputy Secretary of Defense. Memorandum for Secretaries of the Military Departments:  
Expansion of Force Health Protection Anthrax and Smallpox Immunization Programs for 
DOD Personnel.  June 28, 2004.   
178.  The Assistant Secretary of Defense.  Memorandum for Secretaries of the Military 
Departments:  Clarification of Service Responsibilities in Vaccinating Department of 
Defense (DoD) Personnel and Dependents Assigned to Department of State (DoS) 
Missions or Residing in High-Threat Areas, March 13, 2003.   
179.  The Assistant Secretary of Defense.  Memorandum for Secretaries of the Military 
Departments:  Resumption of Anthrax Vaccinations for Personnel Previously Deferred,  
July 28, 2004.   
180.  Under Secretary of Defense. Memorandum for Secretaries of the Military Departments:  
Expansion of Force Health Protection Anthrax and Smallpox Immunization Programs for 
Emergency-Essential and Equivalent Department of Defense Civilian Employees, 
September 22, 2004.   
181.  The Assistant Secretary of Defense. Memorandum for Assistant Secretaries of the Army, 
Navy, and Air Force:  Status Report of Anthrax and Smallpox Vaccinations, February 11, 
2004.   
182.  Department of Defense.  Mil Vax - Smallpox Vaccination Program. Access date:  April 
19, 2004.  Last update date:  April 18, 2005.   
   
 
57 
  Contains Nonbinding Recommendations 
 
APPENDIX 1 
 
EXAMPLE OF A FLOW CHART FOR DETERMINING  
IF A DONOR SPECIMEN IS ADEQUATE FOR  
INFECTIOUS DISEASE TESTING 
 
 
Donor transfused/infused-----No-----Test blood specimen 
               | 
            Yes 
     |     
Donor is an adult-----No-----Recent pre-transfusion/infusion-----Yes-----Test pre-transfusion 
(>12                   blood specimen available                            /infusion blood specimen 
years old)                                        | 
     |                                      No 
     |                                        | 
    Yes                                   Apply algorithm 
     |                                     (See Appendix 2) 
     | 
Recent pre-transfusion/infusion 
blood specimen available             ------Yes------Test pre-transfusion/infusion blood specimen 
               | 
   No 
               | 
Blood loss occurred-----No-----Test blood specimen   
     | 
   Yes 
     | 
Are the following conditions exceeded: 
1. 2000 mL blood or colloid within 48 hours or  
2. 2000 mL crystalloids within 1 hour or 
3. 2000 mL total combination of blood and colloid in last 48     ------No------Test blood specimen                       
  hours with crystalloid in last hour 
     | 
   Yes 
     | 
Apply algorithm 
(see Appendix 2) 
   
58 
  Contains Nonbinding Recommendations 
 
 
ACCOMPANYING QUESTIONS FOR FLOW CHART FOR DETERMINING  
IF A DONOR SPECIMEN IS ADEQUATE FOR  
INFECTIOUS DISEASE TESTING 
 
Question #1  Has the donor had a transfusion or infusion? 
 
  If the answer to question # 1 is no, then test the blood specimen 
  If the answer to question #1 is yes, then ask question #2 
 
 
Question #2  Is the donor an adult? 
 
  If the answer to question #2 is no, then ask question #2a 
  If the answer to question #2 is yes, then ask question #3 
   
   
Question #2a  Is there a recent pre-transfusion/infusion blood specimen available for the donor 
who is twelve years of age or younger? 
  If the answer to question # 2a is no, then apply the algorithm (see appendix 2) 
  If the answer to question #2a is yes, then test the pre-transfusion/infusion blood specimen 
that is available 
 
Question #3  Is there a recent pre-transfusion/infusion blood specimen available for the donor 
who is more than twelve years of age? 
 
  If the answer to Question #3 is yes, then test the pre-transfusion/infusion blood specimen 
  If the answer to Question #3 is no, then ask Question #4 
 
Question #4  Has blood loss occurred? 
 
  If the answer to Question #4 is no, then test the blood specimen 
  If the answer to question number 4 is yes, then ask Question #5 
 
Question #5  Are any of the following conditions exceeded? 
  2000 mL of blood or colloid given to the donor within the past 48 hours; 
  2000 mL of crystalloids within the last hour; or 
  2000 mL total of any combination of blood and colloid within past 48 hours, and 
crystalloid within the past hour 
  If the answer to Question #5 is no, then test the blood specimen 
  If the answer to Question #6 is yes, then apply algorithm (see Appendix 2) 
 
59 
  Contains Nonbinding Recommendations 
 
APPENDIX 2 
EXAMPLE OF AN ALGORITHM 
 
DONOR ID # ____________________ 
 
  Date and Time of Specimen Collection ______________________ 
  Donors weight in kg ____________________ 
   
 
A =      Total volume of blood transfused in the 48 hours before death or sample collection, 
whichever comes first 
      
B =      Total volume of colloid infused in the 48 hours before death or sample collection, 
whichever comes first  
 
C =      Total volume of crystalloid infused in the 1 hour before death or sample collection, 
whichever comes first  
 
BV =   donors blood volume 
 
  Calculated blood volume =  donors weight (kg) / 0.015 OR  
donors weight (kg) x 70 mL/kg  
 
PV =   donors plasma volume 
 
  Calculated plasma volume = donors weight (kg) / 0.025 OR  
  donors weight (kg) x 40 mL/kg 
 
Calculate both: 
 
1.  Is B + C > PV? 
2.  Is A + B + C > BV? 
 
[Enter a zero if a category (A, B, or C) was not transfused/infused.] 
 
Determination of Sample Acceptability for Infectious Disease Tests: 
 
If the answers to both 1 and 2 are NO, the post-transfusion/infusion sample is acceptable. 
 
If the answer to either 1 or 2 is YES, the post-transfusion/infusion sample is not acceptable; use a 
pre-transfusion/infusion sample or reject the donor 
60 
  Contains Nonbinding Recommendations 
 
APPENDIX 3 
 
Example of a Plasma Dilution Worksheet (Using Appendix 2 Algorithm) 
 
Donor ID # _________________                                                     
   Date and Time of Sampling..................................      __________________ am/pm 
  Donor Weight in kg ..........................................            _______________ kg 
  Blood Volume  (BV) = donors weight (kg) _______  0.015 ............ 
                              OR  (BV) = donors weight (kg) _______ X 70 mL/kg.......        _______ mL 
Plasma Volume (PV) = donors weight (kg) _______  0.025 ............   
                               OR  (PV) = donors weight (kg) _______ X 40 mL/kg.......        _______ mL 
 
A.  Total Volume of Blood Transfused/48 hours (before death or sample collection, whichever comes first) 
  Volume of:  RBCs transfused/48 hours            _________  
                               +  whole blood transfused/48 hours  _________                                            A   =  _________ mL 
   
B. Total Volume of Colloid Infused/48 hours (before death or sample collection, whichever comes first) 
  Volume of:      dextran   _________ mL 
      +      plasma   _________ mL 
      +    platelets   _________ mL 
      +    albumin   _________ mL 
      + hetastarch  __________mL 
      +         Other  _________ mL    ____________ 
               __________mL    ____________   
           B    =  _________ mL  
 
C. Total Volume of Crystalloid Infused/1 hour (before death or sample collection, whichever comes first) 
  Volume of:                     saline   __________  mL 
      +  Dextrose in water  __________  mL 
        +     Ringers lactate  __________  mL 
      +                     Other  __________  mL  ____________ 
                __________  mL  ____________                                C    =  _________ mL  
 
Determination of Sample Acceptability for Infectious Disease Tests: 
[Calculate both 1. and 2.  Enter a zero if a category (A, B, or C) was not transfused/infused] 
 
1.  Is B + C > PV?                                                                                                                    Y    N 
2.  IS A + B + C > BV?                         Y   N 
 
*   If the answers to both 1 and 2 are NO, the post-transfusion/infusion sample is acceptable 
*   If the answer to either 1 or 2 is YES, the post-transfusion/infusion sample is not acceptable; use a pre-
transfusion/infusion sample or reject the donor 
 
 
61 
  Contains Nonbinding Recommendations 
 
APPENDIX 4 
 
MODERATE AND SEVERE COMPLICATIONS OF SMALLPOX VACCINATION AND 
INADVERTENT VACCINIA VIRUS INFECTION  
 
Complications of smallpox vaccine or of inadvertent vaccinia virus infection, for the purpose of 
this guidance, are defined as the following, and are consistent with CDC definitions of moderate 
to severe adverse reactions to the smallpox vaccine, or to inadvertent vaccinia virus infection in 
contacts of vaccine recipients (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5010a1.htm).  
 
 
Eczema vaccinatum  
Generalized vaccinia  
Progressive vaccinia  
Postvaccinial encephalitis  
Vaccinial keratitis  
 
Eczema vaccinatum is a localized or systemic dissemination of vaccinia virus in someone with 
eczema (atopic dermatitis) or a history thereof, or with other chronic or exfoliative skin 
conditions.  
 
Generalized vaccinia is characterized by a vesicular rash of varying extent that can occur among 
persons without underlying illnesses.  The rash is generally self-limited and requires minor or no 
therapy except in rare cases, when the vaccine recipient is systemically ill.  
 
Progressive vaccinia (vaccinia necrosum) is a severe, potentially fatal illness characterized by 
progressive necrosis in the area of vaccination, often with metastatic vaccinia lesions.  It has 
occurred almost exclusively among persons with cellular immunodeficiency.  
 
Postvaccinial encephalitis is a rare but serious complication of vaccinia virus infection.  
 
Vaccinial keratitis is an infection of the cornea, which can cause corneal scarring and visual 
impairment. This condition is usually caused by accidental self-inoculation of the eye from the 
vaccine site, or from self-inoculation after contact with another vaccine recipient, and is not 
believed to be due to hematogenous spread or associated with a secondary viremia.  
 
62 
  Contains Nonbinding Recommendations 
 
APPENDIX 5  
 
LIST OF BSE-AFFECTED COUNTRIES APPLICABLE TO DONOR DEFERRAL 
 
European Countries to be Used for Deferral of Donors Based on Geographic Risk of BSE  
 
 
Albania, Austria, Belgium, Bosnia-Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, 
Finland, France, Germany, Greece, Hungary, Ireland, Italy, Liechtenstein, Luxembourg, 
Macedonia, Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain, 
Sweden, Switzerland, United Kingdom1, and Yugoslavia.  
  
 
 
 
 
1For purposes of this guidance, the United Kingdom should include all of the following: 
England, Northern Ireland, Scotland, Wales, the Isle of Man, the Channel Islands, Gibraltar, and 
the Falkland Islands. 
 
  
63 
  Contains Nonbinding Recommendations 
 
APPENDIX 6 
 
West Nile Virus (WNV)  
 
WNV was first identified in the United States in 1999, in an epizootic outbreak among birds and 
horses and an epidemic of meningitis and encephalitis in humans in the New York City area.  
Throughout 2000 - 2001, avian mortality surveillance documented geographic spread to about 
half of the United States. In 2001, 66 human cases of WNV encephalitis or meningitis occurred 
in 10 states.  In 2002, a major epizootic outbreak of WNV was detected in many parts of the 
United States combined with the largest human WNV meningoencephalitis outbreak ever 
documented, and the largest outbreak of meningoencephalitis from any cause in North America.  
In 2002, the number of human cases far surpassed those reported in 2001 with 4,161 cases of 
WNV illness and 277 deaths reported as of March 12, 2003. Ninety-nine percent of the human 
cases occurred between July 1 and October 31, 2002. Human cases were reported in 736 counties 
in 39 states and the District of Columbia. The 2002 WNV epidemic involved the first 
documented cases of WNV transmission through organ transplantation, blood transfusion, and 
possibly breastfeeding (Refs. 149 and 150).  In addition, intrauterine infection was reported (Ref. 
151).  Surveillance reports published weekly in Morbidity and Mortality Weekly Report 
(MMWR) indicated that WNV was active in the United States in 2003 and had spread to 
additional areas of the country as compared to 2002.  Blood establishments began using WNV 
nucleic acid amplification tests (NAT) under investigational drug exemptions (IND) beginning 
late June 2003.  It is estimated that, through 2004, at least 1017 presumptively viremic donations 
were removed from the blood supply as a result of blood establishments voluntary participation 
in WNV NAT screening studies (Ref. 5).  In 2003, a total of 9,862 cases of human illness, 
including 2,775 neuroinvasive disease cases and 264 fatalities were reported to CDC (Refs. 5, 
152, 153, and 154).  In the 2004 WNV epidemic, CDC reported WNV activity in 47 continental 
states, with 2,470 reported human cases and 88 fatalities (Refs. 5, 154, 155, and 156).   
 
WNV has the potential to be spread via HCT/Ps, as evidenced by its transmission via organ 
transplantation, and via blood and blood product transfusion.  Though it is not possible to predict 
the incidence or severity of future WNV epidemics, our experience with the transmission pattern 
of WNV and the rapid geographic spread of the disease epidemic suggests that all or most of the 
United States would be at risk for exposure to the illness each year.  WNV activity in birds and 
mosquitoes has been documented year-round in states with warm winter climates.  Human 
infection in these areas is a theoretical risk at all times of the year (Ref. 5).  
 
Our current recommendation is only for donor screening.  Some HCT/P donors are being tested 
under the IND previously mentioned, though testing with an investigational product is not a 
requirement.   In WNV infection, 80% of persons are asymptomatic, 20% have mild symptoms, 
and only about 1/150 persons experience severe illness.  Because symptoms occur in only 
approximately 20% of persons infected with WNV, donor exclusions based on donor health 
screening will have limited effectiveness.  Laboratory screening tests to detect donor infections 
with WNV will be needed if the epidemic persists.  We may recommend routine use of 
appropriate licensed donor screening test(s) to detect acute infections with WNV using NAT 
64 
  Contains Nonbinding Recommendations 
 
technology once such tests are available.  (See Refs. 5, 6, and 7 for further information regarding 
the background and rationale for WNV deferral.) 
 
Sepsis 
 
For the purpose of this document, sepsis includes, but is not limited to, bacteremia, septicemia, 
sepsis syndrome, systemic infection, systemic inflammatory response syndrome (SIRS), or septic 
shock.  The causative agent in sepsis has been changing over the years.  Fungal pathogens have 
become an increasingly important cause of sepsis.  Gram-negative organisms were the most 
common organisms leading to sepsis between 1979 and 1987, but, by 2000, gram-positive 
organisms caused 52.1% of cases and gram-negative organisms were responsible for about 
37.6% (Ref. 157).   Various bacterial, fungal, and viral agents have been shown to be 
transmissible via HCT/Ps (Refs. 158 through 162) and bacterial infection potentially resulting in 
sepsis with associated morbidity and mortality is a widely recognized risk from transfused blood 
and blood products (Refs. 163 and 164).   
 
A recent study in the New England Journal of Medicine (NEJM) reviewed the epidemiology of 
sepsis in the United States from 1979 through 2000 by looking at discharge data contained in the 
National Hospital Discharge Survey (Ref. 157).  This study showed that the incidence of sepsis 
has been increasing over that time period and estimated the incidence as of 2000 to be 240.4 
cases/100,000 population.  The NEJM study also cited references stating that sepsis is now 
among the top ten leading causes of death in the United States.  Another widely cited sepsis 
study by Angus, et al. reviewed all the 1995 discharge data from a sample of hospitals in 7 states 
that collectively served approximately 25% of the population of the United States (Ref. 165).  
The Angus study estimated the incidence of sepsis over that year to be about 3.0 cases per 1,000 
population and 2.26 cases per 100 hospital discharges.  The Angus study estimated that in 1995, 
about 9.3% of all deaths in the United States were a direct or indirect result of sepsis  similar to 
the number of deaths caused by myocardial infarction over the course of that year.  The mortality 
rate of sepsis in these studies was estimated to be about 17.9% and 28.6%, respectively.  These 
studies (Refs. 157 and 165), as well as others (Refs. 166, 167, and 168), agree that the risk of 
sepsis is increased with age (after one year old), male sex, comorbid illness, and in non-whites.  
The incidence and prevalence of sepsis is widely believed to be increasing (Refs. 157, 165, 166, 
167, and 169). While the mortality rate of sepsis has been decreasing slightly with advances in 
medical care, the overall number of deaths due to sepsis has been increasing (Ref. 157).   
 
Vaccinia  
 
Although there are no documented cases of transmission of vaccinia virus through implantation, 
transplantation, infusion, or transfer of HCT/Ps into a human recipient, FDA believes that 
vaccinia virus is potentially transmissible via HCT/Ps.  Two different investigators, in 1930 and 
1953, reported that vaccinia virus could sometimes be isolated from a patients blood 3-10 days 
after vaccination (Ref. 8). These studies did not use the less virulent NYCBOH strain of vaccinia 
virus that comprises currently available vaccines in the U.S. Using the NYCBOH strain of 
vaccinia virus, other investigators were only able to detect virus in the blood of patients with 
  65 
  Contains Nonbinding Recommendations 
 
disseminated infection, but not in patients who only had localized lesions (Refs. 9 and 10).  
These studies are of limited value, however, because of their small size.  Studies are now 
underway to determine the presence and frequency of vaccinia virus in the blood after 
vaccination.  
 
A frequent complication of smallpox vaccination is autoinoculation or inadvertent inoculation of 
a contact (Refs. 170, 171, and 172).  Vaccinia virus is readily recovered from the vaccination site 
until the vaccination scab spontaneously separates from the skin. The scabs themselves contain 
infectious virus. Thus, although viremia is unlikely once an immune response is initiated, 
recipients of the vaccine could still inadvertently infect contacts that touch the vaccination site or 
dressing (Ref. 173). Vaccinia virus can be recovered from the skin at the vaccination site for a 
mean duration of 7.8 days, with a range of 0 to 18 days (Ref. 174).  After an individual is 
vaccinated with the vaccinia virus, vaccinia can be accidentally spread to other parts of the body 
and to others since the virus is capable of contact transmission (Refs. 11, 172, and 175).  
Nosocomial spread of vaccinia has also been reported (Ref. 172).  Recent literature describes the 
conjugal transfer of vaccinia from 2 different active-duty military personnel to their respective 
partners after smallpox vaccination (Ref. 176). 
 
Smallpox vaccination was routinely performed in the U.S. until 1971. In recent years, smallpox 
vaccination has been recommended only for laboratory personnel working with certain orthopox 
viruses, including vaccinia and smallpox.  On June 20, 2002, the Advisory Committee for 
Immunization Practices (ACIP) of the CDC recommended that smallpox vaccine also be given to 
persons pre-designated to conduct investigation and follow-up of initial smallpox cases and to 
personnel in facilities that are pre-designated to serve as referral centers to provide care for initial 
smallpox cases. On December 13, 2002, President Bush announced his decision to begin a 
smallpox vaccination campaign targeted to those military and civilian personnel who have an 
occupational risk of contracting smallpox.  There is a policy in place to vaccinate Department of 
Defense (DoD) personnel who are deployed to areas designated as high-threat by the Secretary 
of Defense.  In addition, DoD offers voluntary smallpox vaccination for military members and 
their families, civilian employees and their family members, and contract personnel serving at 
Department of State missions in Near East Asia, Israel, Turkey, North Africa, Lebanon, Syria, 
Jordan, Egypt, and Korea (Refs. 177 through 180).  Implementation and review of these policies 
appear to be ongoing (Ref. 181).  According to the DoD Smallpox Vaccination Program website 
(updated 4/14/05) (Ref. 182), more than 760,000 people have been vaccinated with smallpox 
vaccine since December 2002 through its vaccination program.  Since the smallpox vaccination 
program affects a large number of people throughout the country, we believe the incidence of 
vaccinia in the donor population is sufficient to warrant its addition to the list of relevant 
communicable diseases.   
 
 
  66