Use of Nucleic Acid Tests to Reduce 
the Risk of Transmission of West Nile 
Virus from Living Donors of Human 
Cells, Tissues, and Cellular and 
Tissue-Based Products (HCT/Ps)
  
 
 
Guidance for Industry 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or 
from the Internet at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm. 
 
 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration  
Center for Biologics Evaluation and Research  
September 2016 
Corrected May 2017  
Use of Nucleic Acid Tests to Reduce 
the Risk of Transmission of West Nile 
Virus from Living Donors of Human 
Cells, Tissues, and Cellular and 
Tissue-Based Products (HCT/Ps)
  
 
 
Guidance for Industry 
 
 
 
 
NOTE:  A correction has been made to this guidance as follows: 
 
  Under section III.A.1, the Note has been reformatted.    
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
September 2016 
Corrected May 2017  Contains Nonbinding Recommendations 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  Regulatory Background ....................................................................................... 2 
B.  WNV Epidemiology and Public Health Impact ................................................. 3 
C.  Seasonality of WNV in the United States ............................................................ 4 
D.  Transfusion-Transmitted WNV Infection .......................................................... 4 
E.  Transplant-Transmitted WNV Infection ............................................................ 6 
F.  Assay Development and Performance ................................................................ 8 
III.  RECOMMENDATIONS .................................................................................................. 8 
IV.  IMPLEMENTATION .................................................................................................... 10 
V.  REFERENCES ................................................................................................................ 11 
i  Contains Nonbinding Recommendations 
Use of Nucleic Acid Tests to Reduce the Risk of Transmission of 
West Nile Virus from Living Donors of Human Cells, Tissues, and 
Cellular and Tissue-Based Products (HCT/Ps) 
 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
This guidance provides you, establishments that make donor eligibility (DE) determinations for 
donors of HCT/Ps, with recommendations for testing living donors for West Nile Virus (WNV) 
using an FDA-licensed donor screening test.  We (FDA) believe that the use of an FDA-licensed 
nucleic acid test (NAT) will reduce the risk of transmission of WNV from living donors of 
HCT/Ps and therefore recommend that you use an FDA-licensed NAT to test living donors of 
HCT/Ps for evidence of infection with WNV as set forth in this guidance.  This guidance does 
not provide information regarding testing of cadaveric HCT/P donors for WNV.  This guidance 
finalizes the draft guidance entitled Use of Nucleic Acid Tests to Reduce the Risk of 
Transmission of West Nile Virus from Living Donors of Human Cells, Tissues, and Cellular and 
Tissue-Based Products (HCT/Ps); Draft Guidance for Industry dated December 2015 (80 FR 
77645).  This guidance supplements WNV donor screening recommendations in sections IV.E. 
(recommendations 15 and 16) and IV.F. (recommendation 5), and supersedes the West Nile 
Virus (WNV) section in Appendix 6, of the guidance entitled Guidance for Industry:  
Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based 
Products (HCT/Ps) (2007 Donor Eligibility Guidance) dated August 20071 (Ref. 1).  
 
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 The 2007 Donor Eligibility Guidance updated the guidance of the same title dated February 2007 (February 28, 
2007, 72 FR 9007).  
1  Contains Nonbinding Recommendations 
 
II.  BACKGROUND 
 
A.  Regulatory Background 
 
In 2002, test manufacturers and blood organizations, with input from Public Health 
Service representatives (National Institutes of Health (NIH), Centers for Disease Control 
and Prevention (CDC), and FDA), actively pursued development of NAT systems for 
WNV.  A workshop entitled Development of Donor Screening Assays for West Nile 
Virus was held on November 4-5, 2002 (Ref. 2).  The workshop discussed the 
possibility that WNV would be recognized as a relevant communicable disease agent or 
disease for HCT/Ps when appropriate screening measures were developed.   
 
Since 2002, studies have documented human-to-human transmission of WNV by blood 
transfusion and transplantation of vascularized human organs (Refs. 3, 4, 5). 
 
As discussed in the 2007 Donor Eligibility Guidance, FDA determined WNV to be a 
relevant communicable disease agent or disease in accordance with 21 CFR 1271.3(r)(2).  
This determination was based on the severity of the effects of WNV, its incidence and 
prevalence in the donor population, the potential for transmission of WNV by HCT/Ps, 
and the availability of appropriate screening measures.  The 2007 Donor Eligibility 
Guidance contained specific recommendations for donor screening for WNV but not for 
donor testing.   
 
Under 21 CFR 1271.80(a) and 1271.85(a), establishments must perform donor testing to 
adequately and appropriately reduce the risk of transmission of relevant communicable 
disease agents and diseases, unless an exception identified in 21 CFR 1271.90(a) applies.  
An establishment may determine a donor to be eligible only if the results of donor testing 
are negative or nonreactive (21 CFR 1271.50(b)(2)).  However, in 2007, we did not 
recommend testing of HCT/P donors for WNV in recognition of the limited availability 
of such tests.  We stated in the 2007 Donor Eligibility Guidance that we may recommend 
routine use of an appropriate, licensed donor screening test(s) to detect acute infections 
with WNV using NAT technology once such tests were available (Ref. 1). 
 
In April 2008, we published a draft guidance entitled Draft Guidance for Industry:  Use 
of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from 
Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of 
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (Ref. 6).  The 
following year, we finalized the recommendations in that guidance for donations of 
whole blood and blood components in the guidance entitled Guidance for Industry:  Use 
of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from 
Donors of Whole Blood and Blood Components Intended for Transfusion dated  
2  Contains Nonbinding Recommendations 
November 2009 (Ref. 7)2.  In the notice of availability that announced the finalized 
guidance, we stated that we were continuing to review public comments submitted on our 
recommendations for testing HCT/P donor specimens for WNV.  In the notice, we also 
expressed our intention to seek additional public input and to issue guidance for testing 
HCT/P donor specimens for WNV in the future. 
 
In July 2010, the American Association of Tissue Banks (AATB) hosted a public 
workshop entitled, West Nile Virus Workshop:  Scientific Considerations for Tissue 
Donors (Ref. 8).  Workshop participants included subject-matter experts from AATB-
accredited tissue banks (including reproductive tissue banks), Eye Bank Association of 
America (EBAA) representing accredited eye banks, FDA, CDC, the United States 
Department of Health and Human Services (HHS), Health Canada, the Public Health 
Agency of Canada, and other stakeholders.  The goal of the workshop was to develop 
public interest in relevant scientific studies to fill the gaps in the knowledge of WNV in 
human tissues.  The data generated by such studies could further inform regulatory 
decisions regarding HCT/P donor screening and testing for WNV.  
 
In October 2013, we published a revised draft guidance for HCT/Ps entitled Draft 
Guidance for Industry:  Use of Nucleic Acid Tests to Reduce the Risk of Transmission of 
West Nile Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based 
Products (HCT/Ps) to provide establishments that make donor eligibility determinations 
for donors of HCT/Ps, with recommendations for donor testing for WNV using an FDA-
licensed donor screening test (Ref. 9).  The guidance provided information and 
recommendations regarding NAT testing of HCT/P donors for WNV.  
 
B.  WNV Epidemiology in the United States and Public Health Impact 
 
WNV is an arthropod-borne virus (arbovirus) in the family Flaviviridae which has a 
single-stranded ribonucleic acid (RNA).  WNV was first detected in the United States 
(U.S.) in 1999 during an outbreak in the New York City area (Ref. 10).  WNV has 
become endemic with high viral activity during warmer months of the year.  WNV is 
maintained in nature primarily in a mosquito-bird-mosquito transmission cycle 
predominantly involving Culex (Cx.) species mosquitoes (Cx. pipiens, Cx. tarsalis, and 
Cx. quinquefasciatus), but can also infect other animals, such as horses and humans 
(Refs. 10, 11, 12). 
 
Birds are the natural reservoir hosts for WNV.  Many WNV-infected avian species 
develop transient viremia sufficient to infect feeding mosquitoes (Ref. 13).  Birds 
commonly survive their infections and develop permanent immunity, although certain  
                                                 
2 The final guidance, Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from 
Donors of Whole Blood and Blood Components Intended for Transfusion provides recommendations for testing 
blood and blood components which include allowing minipool testing in times of low incidence of WNV.  The 
policy determination regarding the appropriate type of testing recommended to protect the public health is dependent 
on both the epidemiology of the communicable disease, and the characteristics of the product type for which the 
testing applies.     
3  Contains Nonbinding Recommendations 
species become ill and die (Ref. 14).  Humans are considered dead-end hosts for the virus 
since they do not develop viremia sufficient to allow virus transmission to feeding 
mosquitoes (Ref. 15).  
 
Approximately 80% of WNV infections in humans result in an asymptomatic infection.  
The clinical features of WNV infections in the 20% of humans who are symptomatic are 
broad-ranging and vary from febrile illness that includes headache, myalgia, arthralgia, 
rash, or gastrointestinal symptoms (Refs. 16, 17) to the development of neuroinvasive 
disease, which occurs in less than 1% of infected humans.  West Nile virus neuroinvasive 
disease, which typically presents as a panencephalitis, meningitis, or acute flaccid 
paralysis may lead to irreversible neurological damage, coma, and death (Refs. 17, 18, 
19).  From 2002 to 2013, the annual incidence of WNV neuroinvasive disease in the U.S. 
has ranged from 0.12 to 1.02 per 100,000 population, with peaks in 2002, 2003, and 2012 
(Refs. 20, 21, 22, 23, 24).  People over the age of 50 and some immunocompromised 
persons may have a higher risk of developing WNV neuroinvasive disease (Refs. 25, 26). 
 
C.  Seasonality of WNV in the United States 
 
WNV became a nationally notifiable disease in 2002.  Therefore, state and local health 
authorities use standard case definitions to report cases of WNV to CDC via ArboNET 
(Ref. 27).  As noted above, WNV has become endemic in the United States with high 
viral activity during warmer months of the year, which means the HCT/P donor 
population has a higher risk of becoming infected with WNV during these months.  In an 
effort to identify the months during which the risk of infection is greatest, FDA-CBERs 
Office of Biostatistics and Epidemiology performed an analysis of the data collected via 
ArboNET from 1999 through 2013 (provided by CDC) to assess the seasonal and 
geographical patterns of WNV infections in the United States.  Analysis of these data 
indicates that > 98.5% of WNV infections in each region of the United States (50 states 
and the District of Columbia) occur between June 1st and October 31st.  The data also 
indicate that the pattern of seasonal activity has been consistent since the appearance of 
WNV in the United States.  Publically available data that support this observation are 
maintained by CDC (Ref. 28). 
 
Since adequate data for locations outside of the United States (50 states and District of 
Columbia) are not necessarily available for analysis and routine monitoring, 
establishments located outside of the United States (50 states and District of Columbia) 
should not rely upon these analyses to support seasonal testing. 
 
D.  Transfusion-Transmitted WNV Infection 
 
The potential for WNV transmission by blood transfusion was first recognized in 2002 
(Ref. 3).  WNV transmission usually occurs during the acute phase of infection when 
infected individuals are viremic and asymptomatic (Ref. 29).  Few infected donors 
develop clinically significant disease.  Studies have shown that questioning blood donors 
for recent illness suggestive of WNV infection is ineffective at identifying 
infected/seropositive donors (Refs. 30, 31, 32).  During 2002, CDC conducted 
4  Contains Nonbinding Recommendations 
investigations of five blood transfusion recipients who subsequently developed 
neurologic disease.  In four of these five cases, there was WNV-associated disease in the 
blood recipients, including one fatality.  In the fifth of the five transfusion cases, there 
was an unspecified encephalopathy in a recipient of a WNV TaqMan-positive blood 
product, but there was no documentation of seroconversion in this recipient (Ref. 33).  
 
Pealer et al., reported a total of 23 confirmed cases of WNV transmission by blood and 
blood components in 2002, including the five above mentioned investigations reported by 
CDC (Ref. 3).  Of the 23 confirmed cases, 10 (43%) of the patients were 
immunocompromised due to immune suppression related to transplantation or cancer, 
and 8 (35%) were older than 70 years of age.  All 23 infected recipients were linked to 16 
donors with evidence of viremia at the time of donation.  In follow-up studies with the 
donors, 9 of the 16 donors reported viral symptoms before or after donation, five were 
asymptomatic, and two were lost to follow-up.  All 16 donors were immunoglobulin M 
(IgM) seronegative at the time of donation (Ref. 3). 
 
The cases in 2002 involving transfusion-transmitted WNV infection prompted the 
initiation of donor testing in 2003.  In June 2003, blood establishments began to screen 
blood donations for WNV by NAT using two different tests under FDAs Investigational 
New Drug Application (IND) regulations (21 CFR Part 312).  The protocols implemented 
to screen donations included minipool NAT (MP-NAT) testing of samples using 
minipools of either 6 or 16 donations, depending on the manufacturer, followed by 
individual testing (ID-NAT) of each donation that was part of any reactive minipool (Ref. 
19).  Between July 1 and October 31, 2003, blood donor testing by American Red Cross 
(ARC) and participating members of Americas Blood Centers (ABC) yielded 944 
confirmed viremic donors out of 4,585,573 units screened (1 in 4,858 donations),  
thereby preventing the use of approximately 1,500 potentially infectious blood 
components (Ref. 32).   
 
Additionally, in 2003, a total of 36 suspected cases of WNV transfusion-transmitted 
infections were reported to CDC.  Upon investigation, five of the 36 cases were classified 
as probable cases and one was classified as a confirmed case.  In each of these six cases, 
the recipients received blood components from multiple donations; however, only one 
infectious blood component was found in each case.  All six infectious donations had 
been collected between July 29, 2003 and September 18, 2003 and had not been detected 
by MP-NAT (Ref. 34).  
 
Until 2004, all WNV testing in blood donors was performed using MP-NAT.  Late in 
2004, there was a transition from MP-NAT testing to ID-NAT in geographic regions with 
high WNV activity during epidemic periods.  While there were 15 suspected cases of 
transfusion-transmitted WNV infections investigated in 2004, only one probable 
transfusion-transmitted case was documented.  The WNV transmission resulted from a 
blood donation which tested nonreactive in a MP-NAT assay.  In 2005, there were eight 
suspected cases investigated, and there was no documented transfusion-transmitted WNV 
infection (Ref. 34). 
 
5  Contains Nonbinding Recommendations 
Since the implementation of routine screening of blood products for WNV, transfusion-
associated WNV infections have been rare (Refs. 7, 35).  Since implementation of 
screening in 2003, 12 transfusion-associated transmissions of WNV have been 
documented, according to the CDC (Ref. 35).  Most recently, CDC reported a case of 
fatal WNV encephalitis in a severely immunosuppressed patient after probable 
transfusion-associated transmission.  The subsequent investigation suggested that the 
implicated donation contained a level of viral load that was near the limit of detection of 
the NAT assays used for the screening and therefore produced inconsistent results on 
repeat testing (Ref. 35).    
 
In 2006, transfusion-transmitted WNV infection occurred in two immunocompromised 
individuals who experienced onset of WNV neuroinvasive disease after receiving blood 
products from a single infected donor, despite a negative MP-NAT result at the time of 
donation (Ref. 36).  In October 2008, the Louisiana Department of Health (LDH) 
reported two cases of probable transfusion-transmitted WNV infections from a common 
blood donor.  One infection resulted in WNV neuroinvasive disease via organ donation 
from an organ donor who had received blood from a WNV-infected blood donor.  The 
other case resulted in asymptomatic WNV infection directly to the blood transfusion 
recipient (Ref. 37). 
 
E.  Transplant-Transmitted WNV Infection 
 
1.  WNV Transmission via Transplantation of Vascularized Human Organs  
 
WNV is also transmissible via transplantation of vascularized human organs.  
Although organ donors are not always tested for WNV (Refs. 37, 38), multiple 
WNV transmissions via transplantation of vascularized human organs have been 
reported in the published medical literature.  For example, in 2002, a published 
report from CDC identified four recipients of vascularized human organs that 
developed WNV infection (Refs. 4, 39).  Three of the four recipients developed 
WNV neuroinvasive disease, and one recipient died.  The attributed mortality rate 
is therefore 25%.  Additionally, since 2002, there have been at least 14 reported 
cases of WNV infections transmitted to recipients by transplantation of 
vascularized human organs.  In three recipients from a single donor who had a 
febrile illness prior to fatal head injury, retrospective testing of stored donor blood 
samples were reactive for WNV IgM, but not for WNV RNA by NAT testing 
(Ref. 40).  In the remaining 11 cases, there was a probable or confirmed 
transmission via transplantation of vascularized human organs.  Of these 14 cases, 
three (21%) were asymptomatic, one (7%) developed a febrile illness, one (7%) 
was found to be viremic, and nine (64%) developed WNV neuroinvasive disease.  
Of those nine individuals who developed WNV neuroinvasive disease, one (11%) 
resulted in death, three (33%) resulted in coma, two (22%) had severe motor or 
cognitive permanent damage, two (22%) recovered, and one has an unknown 
outcome (Refs. 4, 37, 40, 41, 42, 43). 
 
6  Contains Nonbinding Recommendations 
2.  WNV Transmission via HCT/P Transplantation 
 
The documented transmission of WNV by blood transfusion and transplantation 
of vascularized human organs combined with WNV epidemiology, increasing 
understanding of WNV biology, and experience with transmission of other 
relevant communicable disease agents and diseases by HCT/Ps indicate the 
potential for transmission of WNV by HCT/P transplantation.  HCT/Ps constitute 
a heterogeneous group of products that differ in many ways, such as:  donor 
source (living vs. cadaveric); type of tissue or cell product (hematopoietic 
progenitor cells (HPCs), reproductive, structural tissue); extent of processing and 
storage conditions; recipient clinical condition (otherwise healthy to severely 
compromised).  It is impractical to have different DE testing recommendations for 
every type of HCT/P.  However, for certain emerging infectious diseases such as 
WNV, testing living donors only may be both practical and adequate to reduce the 
transmission by HCT/Ps.   
 
In a reported case of intrauterine transmission for WNV, placenta and umbilical 
cord tissue were PCR-positive for the virus, and umbilical cord blood was 
positive for WNV IgM antibodies (Ref. 44).  The potential for WNV transmission 
through HPCs and certain other HCT/Ps containing live cells is presumably 
similar to that of blood transfusion given the similarities in the product 
composition and donor characteristics (e.g., recovered from similar populations 
composed of healthy, living donors).  Moreover, typical recipients of HPCs are 
severely immunocompromised and are more likely to experience serious 
outcomes as a result of WNV infection.  Therefore, the risk of WNV transmission 
is a particularly important consideration for this patient population.  In 2003, there 
was a published report of two cases of WNV neuroinvasive disease in patients 
receiving HPCs for the treatment of acute myeloid leukemia.  In one of these 
patients, the source of the WNV was not determined; in the other patient, the 
WNV was traced to a blood transfusion (Ref. 45).  More recently, there is a 
published report of WNV transmission as a result of a granulocyte transfusion to a 
patient with persistent neutropenia related to cancer chemotherapy (Ref. 46).  In 
this case, although the donor was tested for WNV, the limited shelf life of the 
granulocyte necessitated transfusion of the patient with the granulocyte apheresis 
product prior to obtaining results of the WNV testing.  Because of the increased 
susceptibility to infection in these immunosuppressed patients, and the potential 
for donors to contract WNV infection between DE determination and HPC 
recovery during certain months, medical practitioners may wish to order 
supplemental testing of the donor at the time of HPC recovery.  This additional 
day of test is not required for determining donor eligibility, but may be a useful 
medical practice in post-HPC transplant care. 
 
Scientific data on the risk of transmission of WNV through transplantation of 
HCT/Ps recovered from cadaveric donors are limited.  The paucity of reports of 
WNV transmission via transplantation of such tissue products may reflect factors 
such as differences in viral load, viral inactivation, or other processing steps 
7  Contains Nonbinding Recommendations 
which differ between tissues.  For example, we note that tissues recovered from 
cadaveric donors for processing to decellularized HCT/Ps typically undergo more 
extensive processing than HCT/Ps donated by living donors, and therefore there 
may be potential for decreased transmissibility of WNV from these HCT/Ps.  We 
continue to recognize the value of future studies to better understand the risk of 
transmission through HCT/Ps of various types, and therefore, the 
recommendations in this guidance are limited to living donors of HCT/Ps. 
 
Scientific data on the risk of transmission of WNV through transplantation of 
HCT/Ps recovered from living donors outside the United States are limited.  We 
continue to recognize the value of future studies to better understand the risk of 
transmission through HCT/Ps of various types recovered outside the United 
States. 
 
F.  Assay Development and Performance 
 
Nationwide clinical studies to evaluate NAT for the detection of WNV were initiated in 
2003 under FDAs IND regulations.  Such large-scale studies were undertaken to help 
ensure blood safety and to determine the efficacy of investigational blood assays to 
prevent the transmission of WNV through blood transfusion because, at that time, there 
was no FDA-licensed screening assay available to detect WNV infection.  Donors of 
HPCs were also tested in this initiative as part of the IND studies. 
 
Since 2005, FDA has approved biologics license applications (BLAs) for NAT assays for 
detecting WNV RNA in plasma specimens from donors of Whole Blood and blood 
components, and blood specimens from donors of organs and tissues.  Two assays that 
are licensed for testing specimens from donors of whole blood and blood components are 
also licensed for testing both living and cadaveric (non-heart-beating) HCT/P donors.  
These assays are intended for use in testing individual donor (ID) specimen from such 
donors.  In addition, these assays may also be used for testing pools of human plasma in 
minipools comprised of equal aliquots of individual donations from volunteer donors of 
Whole Blood and blood components.  
 
 
III.  RECOMMENDATIONS  
 
As noted above and as described at greater length in the 2007 Donor Eligibility Guidance, WNV 
is a relevant communicable disease agent or disease as defined in 21 CFR 1271.3(r)(2).  We now 
determine that testing for WNV is necessary to adequately and appropriately reduce the risk of 
transmission of WNV in living donors of HCT/Ps.  Therefore, FDA recommends that:  
 
8  Contains Nonbinding Recommendations 
A.  Living HCT/P donors should be tested for WNV using an FDA-licensed NAT 
donor screening test.3,4 
 
1.  For establishments located within the United States (includes the 50 states 
and District of Columbia), we recommend performing WNV testing on 
HCT/Ps recovered from June 1st through October 31st every year. 
 
Note:   In the case of a repeat semen donor from whom a specimen has 
already been collected and tested, and for whom retesting is 
required under  1271.85(d), you are not required to collect a 
donor specimen at the time of each donation ( 1271.80(b)(2)).  
However, you should collect a specimen for WNV NAT testing at 
the time of (or within 7 days before or after) the first donation that 
is recovered within the June 1st through October 31st testing period, 
even if an earlier specimen was already collected and tested.  
 
Due to the increased potential for donors, to contract WNV 
infection from June 1st through October 31st, establishments may 
want to consider collecting a specimen for WNV NAT testing at 
the time of (or within 7 days before or after) each donation made 
during this time period. Although this additional testing for 
subsequent donations is not required, any reactive results must be 
considered when making a donor eligibility determination. 
 
2.  For all other establishments not specified above, and intending to import 
HCT/Ps into the United States, testing of HCT/P donors for WNV should 
be performed year-round. 
 
B.  Any HCT/P donor whose specimen tests negative (or nonreactive) for WNV NAT 
should be considered to be negative (or nonreactive) for WNV for purposes of 
determining donor eligibility.5 
 
C.  Any HCT/P donor whose specimen tests positive (or reactive) for WNV must be 
considered ineligible to donate (21 CFR 1271.50(b)(2), 1271.80(d)(1)).  
                                                 
3 This recommendation for testing does not apply to donations that fall within the scope of any of the exceptions 
described in 21 CFR 1271.90(a), including cells and tissues for autologous use; reproductive cells or tissue donated 
by a sexually intimate partner of the recipient for reproductive use; and, in certain circumstances, cryopreserved 
cells or tissue for reproductive use that were originally exempt from the donor eligibility requirements.  In these 
instances, we do not believe that testing for WNV is necessary to adequately and appropriately reduce the risk of 
transmission of WNV in living donors of HCT/Ps. 
4 If a repeat anonymous semen donor, for whom retesting at least 6 months after donation is required under  
21 CFR 1271.85(d), discontinues donations, then you may use the results for WNV obtained at the final donation, or 
any time later than that, as the test of record to qualify that final donation. 
5 FDAs recommendations regarding donor screening for WNV can be found in sections IV.E. and IV.F. of the 2007 
Donor Eligibility Guidance (Ref. 1).  Consistent with this guidance, 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 
should be considered ineligible. 
9  Contains Nonbinding Recommendations 
IV.  IMPLEMENTATION 
 
FDA recommends that you implement the recommendations in this guidance as soon as feasible, 
but not later than 6 months after the final guidance issuance date.  These recommendations apply 
to all HCT/Ps recovered on or after the implementation date.   
10  Contains Nonbinding Recommendations 
V.  REFERENCES  
 
1.  Food and Drug Administration, Guidance for Industry:  Eligibility Determination for 
Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (August 2007).  
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulator
yInformation/Guidances/Tissue/UCM091345.pdf 
 
2.  Food and Drug Administration, Workshop on Development of Donor Screening Assays 
for West Nile Virus (November 4-5, 2002). 
http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetin
gsConferences/TranscriptsMinutes/UCM054461.pdf. 
 
3.  Pealer LN, et al., Transmission of West Nile Virus through Blood Transfusion in the 
United States in 2002.  N Engl J Med, 2003; 349:1236-1245.  
 
4.  Iwamoto M, et al., Transmission of West Nile Virus from an Organ Donor to Four 
Transplant Recipients.  N Engl J Med, 2003; 348: 2196-2203.  
 
5.  Mezochow AK, et al., Transfusion Transmitted Infections in Solid Organ 
Transplantation.  Am J of Trans, 2015; 15:547-554. 
 
6.  Federal Register Notice:  Food and Drug Administration, Draft Guidance for Industry:  
Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from 
Donors of Whole Blood and Blood Components Intended for Transfusion and Donors of 
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Availability 
(April 28, 2008, 73 FR 22958). 
 
7.  Food and Drug Administration, Guidance for Industry:  Use of Nucleic Acid Tests to 
Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and 
Blood Components Intended for Transfusion (November 2009). 
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulator
yInformation/Guidances/Blood/UCM189464.pdf. 
 
8.  Brubaker SA, Rigney P, West Nile Virus Workshop:  Scientific Considerations for Tissue 
Donors.  Cell Tissue Bank, 2012; 499-511. 
 
9.  Federal Register Notice:  Food and Drug Administration, Draft Guidance for Industry:  
Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from 
Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); 
Availability (October 24, 2013, 78 FR 63476). 
 
10.  Nash D, et al., The outbreak of West Nile Virus Infection in the New York City Area in 
1999.  N Engl J Med, 2001; 344:1807-1814. 
 
11.  Hayes CG, West Nile fever.  In:  Monath TP, ed.  The arboviruses:  epidemiology and 
ecology, Vol V. Boca Raton, FL:  CRC Press, 1989; 59-88. 
11  Contains Nonbinding Recommendations 
 
12.  Turell MJ, et al., An Update on the Potential of North American Mosquitoes (Diptera: 
Culicidae) to Transmit West Nile Virus.  J Med Entomol, 2005; 42:57-62. 
 
13.  Work TH, et al., Indigenous Wild Birds of the Nile Delta As Potential West Nile Virus 
Circulating Reservoirs.  Am J Trop Med Hyg, 1955; 4:872-888. 
 
14.  Komar N, et al., Serologic Evidence for West Nile Virus Infection in Birds in the New 
York City Vicinity During an Outbreak in 1999.  Emerg Infect Dis, 2001; 7:621-625. 
 
15.  Hayes EB, et al., Epidemiology and Transmission Dynamics of West Nile Virus Disease. 
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12  Contains Nonbinding Recommendations 
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13  Contains Nonbinding Recommendations 
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