Guidance for Industry 
 
Assessing Donor Suitability and Blood 
and Blood Product Safety in Cases of 
Known or Suspected West Nile Virus 
Infection 
 
 
 
 
 
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 Blood Applications, Office 
of Blood Research and Review at 301-827-3524. 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
June 2005 Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
I.  INTRODUCTION............................................................................................................1 
II.  BACKGROUND..............................................................................................................2 
A.  U.S. Experience with WNV.................................................................................2 
B.  WNV Transmission by Blood Transfusion........................................................5 
III.  RECOMMENDATIONS FOR DONOR DEFERRAL................................................7 
A.  Diagnosed or Suspected Acute WNV Illness or Infection................................7 
B.  Presumptive Viremic Donors..............................................................................8 
C.  Suspected WNV Illness in a Donor....................................................................8 
D.  Donors Who May Have Transmitted WNV Infection......................................8 
IV.   RECOMMENDATIONS FOR RETRIEVAL AND QUARANTINE OF BLOOD 
AND BLOOD COMPONENTS INCLUDING RECOVERED PLASMA, SOURCE 
PLASMA, AND SOURCE LEUKOCYTES..................................................................9 
A.  Diagnosed WNV Infection or Illness in a Donor...............................................9 
B.  Presumptive Viremic Donors..............................................................................9 
C.  Donors Who May Have Transmitted WNV Infection......................................9 
D.  Undiagnosed Post-Donation Illness in Potentially Exposed Individuals......10 
V.  RECOMMENDATIONS ON NOTIFICATION OF PRIOR TRANSFUSION 
RECIPIENTS.................................................................................................................10 
VI.  BIOLOGIC PRODUCT DEVIATION AND FATALITY REPORTING................11 
VII.  LABELING OF PRODUCTS DISTRIBUTED FOR RESEARCH OR INTENDED 
FOR FURTHER MANUFACTURING INTO NON-INJECTABLE PRODUCTS11 
VIII.  IMPLEMENTATION...................................................................................................12 
IX.  REFERENCES...............................................................................................................13 
 
 
i  Contains Nonbinding Recommendations 
Guidance for Industry 
 
Assessing Donor Suitability and Blood and Blood Product Safety in 
Cases of Known or Suspected West Nile Virus Infection 
 
 
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 
 
This guidance document finalizes the 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, and provides revisions to our previously published final guidance 
entitled Guidance for Industry:  Revised Recommendations for the Assessment of Donor 
Suitability and Blood and Blood Product Safety in Cases of Known or Suspected West Nile 
Virus Infection, dated May 2003.  We, FDA, recommend that these revised recommendations 
be applied prospectively, i.e., that actions taken under previous guidance do not need to be 
reconsidered subject to the additional provisions of this guidance.  This guidance revises the 
final May 2003 West Nile Virus (WNV) guidance to add a recommendation to defer donors 
suspected of having WNV infection or diagnosed with WNV infection for 120 days after 
diagnosis or onset of illness, whichever is later. 
 
This guidance further recommends that donors be deferred on the basis of a reactive 
investigational screening test for WNV.  At their discretion, blood establishments may reenter 
such donors after 120 days from the date of their reactive donation.  Although we are not at this 
time recommending additional testing of the donor during the recommended 120 day deferral 
period, individual donation testing using a nucleic acid test (IDT NAT) for WNV on a follow-up 
sample obtained during the 120 day deferral period will provide useful additional scientific 
information on the duration of WNV viremia in donors.  If such a follow-up sample is reactive 
for WNV, we recommend that the donor be deferred for an additional 120 days from the date the 
sample was collected. 
 
This guidance applies to Whole Blood and blood components intended for transfusion and blood 
components intended for use in further manufacturing into injectable products or non-injectable 
products, including recovered plasma, Source Leukocytes and Source Plasma.  Within this 
document, donors refers to donors of all such products, and you refers to blood 
establishments.  We use the term typical WNV season to mean May 1 to November 30; 
however, isolated WNV infections may occur at any time during the year.  We recommend that 
1  Contains Nonbinding Recommendations 
your Medical Director monitor reports of epizootic activity or human transmission of WNV in 
your local area throughout the year.  We developed the recommendations in this guidance in 
consultation with other Public Health Service agencies of the Department of Health and Human 
Services (HHS).  This guidance does not apply to human cells, tissues, and cellular and tissue-
based products that are subject to 21 Code of Federal Regulations (CFR) Part 1271. 
 
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. 
 
 
II.  BACKGROUND 
 
WNV is an arthropod-borne virus that belongs to the Japanese encephalitis complex of 
flaviviridae.  WNV is a small (50nm) spherical, lipid-enveloped virus enclosing a single-
stranded positive sense ribonucleic acid (RNA) genome of approximately 11,000 nucleotides 
that lacks a 3 prime poly A tract.  The viral genome encodes a polyprotein that is further 
processed to form three viral structural proteins (capsid, membrane, and envelope) and seven 
nonstructural proteins.  While only limited data specific to the inactivation of WNV are 
available, other members of the flaviviridae family are inactivated by heat or solvent detergent 
treatments used to prepare plasma derivatives. 
 
WNV is primarily transmitted in birds through mosquito bites while humans are incidental hosts.  
Incidental mosquito borne infection may also occur in other mammals including horses, cats, and 
domestic animals.  WNV outbreaks have been reported in Europe, the Middle East, and Russia 
during the past decade and have been associated with human encephalitis and meningitis.  A 
poliomyelitis-like illness of acute asymmetrical flaccid paralysis in the absence of pain or 
sensory loss has also been reported. 
 
A.  U.S. Experience with WNV 
 
WNV was first identified in the United States in 1999 as 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.  The 2002 epidemic of WNV 
neuroinvasive disease was the largest ever reported.  In 2002, 4,156 cases of human 
illness were reported, including 2,946 neuroinvasive disease cases and 284 fatalities.  In 
2003, a total of 9,862 cases of human illness, including 2,775 neuroinvasive disease cases 
and 264 fatalities, were reported.  While more human illnesses were reported in 2003 
than in 2002, the number of neuroinvasive disease cases and fatalities were comparable.  
In 2002, 28% of the cases reported were West Nile fever; in 2003, 69% were West Nile 
fever.  The Centers for Disease Control and Prevention (CDC) stated in 2002 that West 
Nile fever is underreported, but as described above, reporting increased in 2003 due in 
2  Contains Nonbinding Recommendations 
part to increased awareness by public health providers and officials, the availability of 
two FDA-cleared WNV diagnostic tests, and the widespread use of the investigational 
WNV NAT in the blood donation setting.  The 2002 WNV epidemic involved the first 
documented cases of WNV transmission through organ transplantation, blood transfusion 
and possibly breastfeeding (Refs. 1-3).  In addition, intrauterine infection was reported.  
Based upon two years of epidemiologic observation, it appears that the peak WNV 
epidemic period occurs in August to late September and abates as female mosquitoes 
enter diapause (dormant state) and stop biting. 
 
In the 2004 WNV epidemic, CDC reported WNV activity in 47 continental states, with 
2,470 reported human cases and 88 fatalities (Ref. 2).  A total of 199 presumptive WNV 
NAT reactive donors were observed in 28 states.  Although the reported levels of human 
infection were lower than the same period in 2003, projections for the distribution and 
extent of WNV infection in 2005 are unknown.  CDC advised that it is likely that WNV 
activity may still occur in areas that experienced high levels of epidemic and epizootic 
infection in previous years.  The earliest onset of human infection in the United States 
was in July 2000 and 2001; May 2002; and April 2003 and 2004.  However, 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. 
 
The pre-clinical incubation period is thought to range from 2 to 14 days following 
infection by mosquito bite.  Although most people infected with WNV (~80%) remain 
asymptomatic, approximately 20% of those infected will develop mild symptoms, which 
are often indistinguishable from other viral infections.  These symptoms may include 
fever, headache, body aches, gastrointestinal complaints, eye pain, or occasionally 
generalized rash or swollen lymph nodes.  Limited published data prior to 2004 
suggested that a transient WNV viremia occurs within 1 to 3 days following WNV 
infection by mosquito bite, and lasts 1 to 11 days (with a mean of 6 days).  Longer 
periods of viremia were noted in some patients with advanced malignancies or who were 
taking immunosuppressive drugs (Ref. 4).  More recently, viremia in asymptomatic 
donors has been shown to persist for longer periods of time, including 104 days after 
initial detection by NAT in a single donor (see below).  However, studies are ongoing.  It 
is estimated that 1 in 150 persons infected with WNV develops a more severe form of the 
disease.  Among individuals with severe disease, fatality-to-case ratios range from 4 to 
14%, with higher ratios in older age groups. 
 
Preliminary evidence suggests that solid organ recipients are at increased risk of 
neuroinvasive disease, perhaps due to their immunocompromised condition.  The risk of 
neuroinvasive disease in persons who are immunocompromised (e.g., due to AIDS or 
primary immune deficiencies) is unknown.  Severe illness may include encephalitis, 
meningitis, meningoencephalitis, or acute flaccid paralysis, which may occur singly or in 
combination.  Symptoms may include:  headache, high fever, neck stiffness, stupor, 
disorientation, coma, tremors, convulsions, and muscle weakness or paralysis.  Severe 
symptoms may last weeks to months, and some permanent neurologic impairment may 
occur.  Currently, treatment for WNV disease is supportive.  In severe cases, this often 
3  Contains Nonbinding Recommendations 
involves hospitalization, intravenous fluids, respiratory support, and prevention of 
secondary infections.  Case fatalities among patients who were hospitalized in the United 
States with severe WNV illness have ranged from 10 to 14%.  CDC has designated WNV 
encephalitis as a nationally notifiable arboviral encephalitides (Refs. 4 and 5). 
 
In 2003, FDA cleared WNV antibody tests that separately detect Immunoglobulin G 
(IgG) or Immunoglobulin M (IgM) anti-WNV antibodies for use in the diagnosis of 
WNV infection (PanBio Limited and Focus Technologies, Inc.).  Additionally, HHS, 
through FDA, encouraged the development and implementation of investigational WNV 
NAT for detection of WNV RNA in the blood donation setting.  In June 2003, blood 
banks began participating in studies under FDAs Investigational New Drug (IND) 
regulations involving the use of investigational NATs from two test-kit manufacturers.  
Initial screening protocols included NAT performed on mini-pools (MP NAT) of samples 
from six or 16 donations, depending on the test-kit manufacturer.  Reactive mini-pools 
were resolved by IDT NAT.  In addition, selected blood banks in areas with high 
epidemic activity implemented IDT NAT screening during limited periods of the 
epidemic season.  Donations that were IDT NAT reactive were not released for 
transfusion, and donors were deferred from donation.  It is estimated that, through 2004, 
at least 1,017 presumptively viremic donations were removed from the blood supply as a 
result of blood establishment's voluntary participation in WNV NAT screening studies. 
 
In the studies, many of the donors of NAT reactive samples identified by either screening 
method agreed to participate in follow-up studies to confirm WNV infection and evaluate 
the persistence of WNV RNA in blood samples collected subsequently.  Certain studies 
have shown that blood donors found to be WNV-positive at the time of donation may, in 
rare instances, demonstrate a low level viremia in the presence of IgM antibodies for as 
long as 49 days after initial NAT reactivity (mean duration 20.5 days).  The estimated 
range for duration of viremia of 6.5 to 56.4 days represented 99% of the population in 
one mathematical model with a time to loss of viremia of 48 days for 99% of the 
population following detection by MP NAT (Ref. 6).  A second model, using a different 
donor base but including the donor detected at 49 days, estimated 31 days to negative 
RNA by individual donor NAT from the index reactive donation for 99% of the 
population.  These investigational studies are ongoing.  In one unpublished study, a 
single donor was found to be IDT NAT reactive after 104 days on one of five replicate 
tests.  Additionally, preliminary data from FDA laboratories have indicated WNV 
infectivity in blood from 7 of 16 WNV NAT reactive individuals who were also 
seropositive for WNV antibodies, when inoculated into Vero cell and human macrophage 
tissue cultures.  These data indicate that live virus may circulate despite the presence of 
antibodies to WNV, but do not clarify whether blood components obtained from 
individuals at this stage of infection can transmit WNV. 
 
At this time, we believe WNV is unlikely to be transmitted through derivatives 
manufactured from plasma, since lipid-enveloped RNA viruses such as WNV would be 
removed and/or inactivated during manufacture of plasma derivatives (Ref. 7).  Although 
direct studies on the clearance of WNV during manufacturing of plasma derivatives are 
limited (Refs. 7-10), licensed plasma derivatives undergo intentional viral clearance 
4  Contains Nonbinding Recommendations 
procedures that are validated to be effective against lipid-enveloped RNA viruses.  These 
procedures include filtration, heating, acidification, and solvent/detergent treatment.  We 
intend to revise these recommendations as appropriate as new scientific information 
about the safety of plasma derivatives becomes available. 
 
B.  WNV Transmission by Blood Transfusion 
 
Between August 28, 2002 and March 1, 2003, the CDC received reports of 61 possible 
cases of transfusion transmitted WNV infection.  Epidemiological investigations and 
testing of available retained donor blood samples demonstrated that blood transfusion 
was a confirmed source of WNV infection in 23 of these cases, with 19 cases remaining 
inconclusive.  West Nile Virus infection was ruled out in the remaining 19 cases.  Fifteen 
confirmed WNV post-transfusion cases had symptomatic illness, including 13 with 
meningoencephalitis and two with fever.  Onset of illness was between 2 and 21 days 
(median 10 days) after the implicated transfusion.  Fourteen WNV viremic donors were 
implicated in the 23 transfusion-associated cases.  Seven instances of transmission to two 
or more patients occurred when the patients received different blood components derived 
from a single blood donation subsequently found to have evidence of WNV.  Nine of the 
14 donors reported symptoms compatible with WNV infection before or after donation.  
In four instances, WNV was isolated from the withdrawn unit of frozen plasma collected 
as part of the suspect donation, indicating that the virus can survive in frozen blood 
components (Ref. 11).  In addition to these patients, investigations in Georgia and Florida 
have demonstrated transmission of WNV in four recipients of solid organs from a single 
organ donor (Ref. 12). 
 
During May to December 2003, an additional 23 suspected cases of WNV transfusion 
transmission were reported to CDC.  Of these 23 cases, public health authorities reported 
15 suspected cases of WNV transfusion transmission among patients who had WNV 
illness after receiving transfusions.  The other eight suspected cases were in recipients of 
components derived from low-level viremic donations that were identified during special 
retrospective studies of MP NAT negative blood retested with IDT NAT by two blood 
organizations.  Follow-up of these eight cases was performed to determine whether WNV 
infection had resulted from the implicated transfusions.  As a result of these 23 
investigations, six cases were classified as confirmed or probable WNV transmission by 
transfusion, 11 as non-cases, and six cases remained unresolved.  Retained donation 
samples from four of the six confirmed or probable cases had a low viral titer (~0.11 
pfu/ml) (Ref. 3). 
 
5  Contains Nonbinding Recommendations 
In 2004, there was one confirmed case of WNV transmission attributed to blood screened 
by investigational MP NAT.  The case resulted in severe WNV encephalitis in the 
recipient.  The source of the infection was identified as a platelet transfusion for which 
plasma aliquot had been saved.  This plasma was subsequently shown to have low level 
WNV viremia by an investigational IDT NAT.  Seroconversion of the donor was also 
observed at the time of follow-up (Ref. 13).  To assist in identification of other possible 
cases of WNV infection potentially associated with transfusion, state and local public 
health authorities report to CDC cases where patients with diagnosed WNV infection 
have received blood transfusions or organs within the eight weeks preceding the onset of 
symptoms.  In addition, the Public Health Service has requested that cases of WNV 
infection in donors who had onset of symptoms within two weeks of blood or organ 
donation be reported to CDC through state and local public health departments.  
Retention by blood establishments of potentially affected blood products (e.g., frozen 
plasma units from donors whose red cells or platelets were given to the affected 
recipient), and, where available, samples of blood and tissue from the affected recipients 
may facilitate the epidemiological investigation in such cases. 
 
On August 17, 2002, we issued an alert to blood establishments entitled Information 
about WNV and Blood Safety which was updated on October 3, 2002.  We urged blood 
establishments to pay careful attention to their existing procedures to screen donors for 
symptomatic infection.  We also recommended that when cases of probable or proven 
WNV infection are discovered post-donation, medical directors of blood establishments 
carefully evaluate the potential need for component quarantine and retrieval and consult 
FDA if necessary. 
 
On October 25, 2002, we issued guidance to industry, Recommendations for the 
Assessment of Donor Suitability and Blood and Blood Product Safety in Cases of Known 
or Suspected West Nile Virus Infection.  On May 1, 2003, we issued revised guidance to 
industry to recommend deferral of donors who reported fever with headache in the week 
before donation.  Additionally, we recommended that blood establishments actively 
encourage donors to report post-donation illnesses that could be associated with infection 
by WNV.  Our previous guidance recommended that donors be deferred for a period of 
28 days based on information from older studies of the longest known viremia. 
 
At the time we issued the May 2003 revised guidance, investigational donor screening for 
WNV infection was not yet available.  Limited donor interview data were available 
regarding possible WNV-related symptoms that occurred in a period of three weeks prior 
to an implicated donation.  Based upon the potential for a combination of these symptoms 
to be predictive of early WNV infection in the absence of testing, we recommended the 
deferral of donors reporting fever with headache in the week prior to donation.  We 
recognized at that time that symptoms occur in only approximately 20% of persons 
infected with WNV and that only a portion of the implicated donors reported symptoms 
prior to donation. 
 
At the October 22, 2004, meeting, the Blood Products Advisory Committee (BPAC) 
heard scientific presentations that viremia associated with WNV infection rarely 
6  Contains Nonbinding Recommendations 
extended up to 49 days following a WNV NAT-positive donation.  Data presented at the 
October 2004, BPAC meeting (Ref. 6) also indicated that self-reported fever with 
headache in the past week before donation did not appear to be predictive of WNV 
infection and did not correlate with peak periods of WNV incidence as determined by 
WNV NAT prevalence in the donor pool.  Based upon these data, we no longer 
recommend donor deferral based upon a reported history of headache with fever in the 
week prior to donation. 
 
We are continuing to consult with experts on WNV at the CDC and elsewhere to ensure 
the safety of the blood supply from WNV infection.  Epidemiological and laboratory 
investigations are rapidly evolving; therefore, we will evaluate promptly any new data or 
experiences related to this issue and provide further updates as appropriate. 
 
The prevalence of WNV seropositivity among blood donors in 2003 and 2004 indicates 
that WNV NAT testing of donated blood in response to annual epidemics is likely to 
continue for the foreseeable future.  The Public Health Service has worked with device 
manufacturers and blood organizations to facilitate the availability of investigational tests 
and to develop more focused testing strategies for areas of high infection incidence, and 
we are working with manufacturers to make licensed tests available in the near future. 
 
 
III.  RECOMMENDATIONS FOR DONOR DEFERRAL 
 
Donors must be in good health at the time of donation and free of diseases transmissible by 
blood (21 CFR 640.3 and 640.63).  Standard procedures that are already in place should result in 
deferral of potentially infected individuals who have symptoms consistent with WNV illness at 
the time of donation.  Such individuals are likely to manifest fever, headache, eye pain, body 
aches, a generalized skin rash, or swollen lymph nodes.  
 
The following recommendations apply to cases of known or suspected WNV illness, or active 
infection.  Although there are limited data on the natural course of WNV infection, the deferral 
periods we are recommending are based on a 14 day asymptomatic incubation period and a 120 
day potential viremic period, which includes all known observations of prolonged viremia plus 
an additional margin of safety. 
 
A.  Diagnosed or Suspected Acute WNV Illness or Infection 
 
In the course of routine medical screening, donors may volunteer symptom histories that 
reflect WNV infection.  We recommend that you defer a potential donor with a medical 
diagnosis or suspicion of WNV infection (based on symptoms and/or laboratory results) 
7  Contains Nonbinding Recommendations 
for 120 days following diagnosis or onset of illness, whichever is later.  At your 
discretion, you may reenter such donors after the 120 day deferral period.1  
 
In the absence of a WNV compatible illness in the previous two weeks, an IgM positive 
WNV antibody test result alone should not be grounds for deferral provided that the 
donor was tested and found to be negative for WNV by MP or IDT NAT at the time of 
collection. 
 
B.  Presumptive Viremic Donors 
 
We recommend that you defer a donor who has tested reactive for WNV infection using 
the investigational WNV NAT donor screening tests.  At your discretion, you may 
reenter such donors after 120 days from the date of their reactive donations (see footnote 
1). 
 
C.  Suspected WNV Illness in a Donor 
 
We recommend that donors who report an otherwise unexplained post-donation febrile 
illness with headache or other symptoms suggestive of WNV infection (i.e., flu-like 
symptoms that include fever with headache, eye pain, body aches, generalized weakness, 
new skin rash or swollen lymph nodes or other evidence of WNV infection) within two 
weeks after donation during the typical WNV season (or at other times when your 
Medical Director determines that there is evidence of local WNV activity), be deferred 
for 120 days following the onset of illness. 
 
D.  Donors Who May Have Transmitted WNV Infection 
 
We recommend that blood donors whose blood or blood components were potentially 
associated with a transfusion-related WNV transmission be deferred for 120 days 
following the date of donation.  At your discretion, you may reenter such donors after 
120 days from the date of donation (see footnote 1).  The following sites provide 
information that may be helpful to blood establishments in counseling blood donors: 
 
http://www.cdc.gov/ncidod/dvbid/westnile/clinical_guidance.htm 
http://www.cdc.gov/ncidod/dvbid/westnile/city_states.htm 
  
 
 
                                                 
1 As discussed in the introduction to this guidance, we are not at this time recommending additional testing of the 
donor during the recommended 120 day deferral period.  However, we encourage you to perform IDT NAT for 
WNV on a follow-up sample obtained from such donors during the 120 day deferral period because of the 
additional scientific information that might be obtained on the duration of WNV viremia in donors.  If a follow-up 
sample is reactive for WNV, we recommend that the donor be deferred for an additional 120 days from the date the 
sample was collected. 
8  Contains Nonbinding Recommendations 
IV.  RECOMMENDATIONS FOR RETRIEVAL AND QUARANTINE OF BLOOD 
AND BLOOD COMPONENTS INCLUDING RECOVERED PLASMA, SOURCE 
PLASMA, AND SOURCE LEUKOCYTES 
 
As a prudent measure to address the possible risk of transmission of WNV by blood transfusion, 
we are providing revised recommendations for component retrieval and quarantine related to 
reports of post-donation illnesses in the donor, or association with WNV infection in recipients 
of blood. 
 
During a typical WNV season, we recommend that you actively encourage donors to report 
unexplained post-donation febrile illnesses with headache or other symptoms suggestive of 
WNV infection (i.e., flu-like symptoms that include fever with headache, eye pain, body aches, 
generalized weakness, new skin rash or swollen lymph nodes) occurring within two weeks after 
blood donation. 
 
A.  Diagnosed WNV Infection or Illness in a Donor  
 
We recommend that in-date components from relevant collections be quarantined and 
retrieved promptly if a donor later reports a medical diagnosis of WNV.  Relevant 
collections include those occurring between an asymptomatic incubation period of 14 
days prior to onset of illness and up to and including 120 days after diagnosis or onset of 
illness, whichever is later.  Absent a recent compatible illness, a positive WNV antibody 
test result alone should not be grounds for product quarantine and retrieval provided that 
the donor did not test positive for WNV by MP or IDT NAT at the time of collection. 
 
B.  Presumptive Viremic Donors 
 
We recommend that in-date components from relevant collections be quarantined and 
retrieved promptly if a donor has tested reactive for WNV infection using the 
investigational WNV NAT donor screening test.  Relevant collections include those 
occurring between 120 days prior to the date of the reactive test and 120 days after the 
date of the reactive test. 
 
C.  Donors Who May Have Transmitted WNV Infection 
 
Based on the observation that time to development of illness may be prolonged in some 
blood recipients, we consider a donor to be potentially associated with transmission of 
WNV if a recipient of blood or transfusible blood components is diagnosed with WNV 
and received blood components from the donor within the 120 days before the onset of 
symptoms in the recipient.  The collections from which the infected recipient received a 
blood component are regarded as suspect donations.  We recommend that you conduct 
prompt product quarantine and retrieval for in-date components collected from the donor 
of a suspect donation in the period between 120 days before the suspect donation and up 
to and including 120 days after the suspect donation. 
 
 
9  Contains Nonbinding Recommendations 
D.  Undiagnosed Post-Donation Illness in Potentially Exposed Individuals 
 
We recommend that you conduct quarantine and retrieve in-date prior collections only if 
your medical director concludes that a donors febrile illness represents likely infection 
by WNV, taking into account whether the illness occurs during the typical WNV season, 
or following donor exposure in an area with an extended outbreak of WNV.  Current 
information on WNV activity in different geographical areas can be found at 
http://www.cdc.gov/ncidod/dvbid/westnile/city_states.htm, or by contacting the local or 
state public health department.  WNV data from state health departments (by county) can 
also be accessed at http://www.npic.orst.edu/wnv/states.htm. 
 
When you decide to quarantine and retrieve in-date prior collections, we recommend that 
you do so promptly, and include the current donation and any others that date back to an 
asymptomatic incubation period of 14 days prior to the onset of symptoms in the donor 
and 120 days after onset of symptoms.  We do not recommend that quarantine or retrieval 
of blood or blood components be performed for otherwise suitable donors who report 
mild symptoms of upper respiratory infection unassociated with fever or for donors who 
only report mosquito bites. 
 
In the event that you decide to conduct quarantine and retrieval of Source Plasma, 
recovered plasma or Source Leukocytes, we do not recommend quarantine and retrieval 
of those products once they have been pooled for fractionation.  We have reviewed the 
viral reduction processes in place for all plasma derivatives.  The methods in place have 
been validated to inactivate flaviviruses related to WNV. 
 
 
V.  RECOMMENDATIONS ON NOTIFICATION OF PRIOR TRANSFUSION 
RECIPIENTS 
 
A blood establishment may receive information that a donor has a medical diagnosis of WNV 
that is relevant to prior donations.  We recommend that establishments that receive such 
information consider tracing records and notifying transfusion services so that they, in turn, may 
consider notifying treating physicians of prior recipients of blood and blood components 
collected from that donor.  We consider relevant units to be those dating from an asymptomatic 
incubation period of 14 days prior, through 120 days after, the onset of illness in the donor.  If a 
post-donation illness is not diagnosed as WNV infection, we do not recommend that you 
consider record tracing and notification of the transfusion services to identify prior recipients of 
blood and blood components collected from that donor. 
 
In cases where an epidemiological investigation suggests that a specific donor is the likely 
source of transmission of WNV to a transfusion (e.g., WNV infection was later confirmed in the 
donor, and the donor was the sole source of blood received by the affected recipient; or multiple 
blood component recipients developed WNV infection and had the donor in common), we 
recommend that blood establishments consider tracing records and notifying transfusion services 
so that they, in turn, may consider notifying treating physicians of prior recipients of relevant 
units of blood and blood components collected from that donor.  We consider relevant units to be 
10  Contains Nonbinding Recommendations 
those dating from 120 days prior, to 120 days subsequent to, the date of the donation that was 
implicated in transmission of WNV.  However, in cases where a donor is potentially associated 
with a case of transmission of WNV, but the epidemiological investigation has not established 
the specific donor as a likely source of transmission of WNV, we do not recommend that you 
consider notifying the transfusion services. 
 
 
VI.  BIOLOGIC PRODUCT DEVIATION AND FATALITY REPORTING  
 
Regulations on Reporting of Product Deviations by Licensed Manufacturers, Unlicensed 
Registered Blood Establishments, and Transfusion Services are in 21 CFR 606.171.  Under these 
regulations, you must submit biological product deviation reports when you distribute a product 
and an event occurred while the product was in your control.  An event is reportable if it is 
associated with product manufacture and it either represents a deviation from current good 
manufacturing practice or specifications that may affect the safety, purity, or potency of the 
product, or represents an unexpected or unforeseeable event that may affect the safety, purity, or 
potency of the product.  The receipt of post donation information concerning a diagnosed or 
suspected WNV infection would be reportable under this section, because collection from a 
donor who may have been infectious at the time of donation would be an unexpected event that 
may affect the safety, purity, or potency of the product.  Additionally, if a suspect donation 
results in fatality in a transfusion recipient, you must report the fatality to the FDA (21 CFR 
606.170(b)). 
 
 
VII.  LABELING OF PRODUCTS DISTRIBUTED FOR RESEARCH OR INTENDED 
FOR FURTHER MANUFACTURING INTO NON-INJECTABLE PRODUCTS  
 
We recommend that quarantined components described in Section IV. above, that are distributed 
for further manufacturing into non-injectable products or for research use, be labeled consistent 
with recommended labeling described below: 
 
Biohazard; 
 
Collected from a donor determined to be at risk for West Nile Virus, or Collected from a 
donor positive for evidence of infection with West Nile Virus; and 
 
For laboratory research use only or Intended only for further manufacturing into non-
injectable products, whichever is applicable.  
 
11  Contains Nonbinding Recommendations 
 
VIII.  IMPLEMENTATION  
 
We recommend that you implement the recommendations in this guidance as soon as feasible, 
but not later than 30 days after issuance of this guidance.  Consistent with 21 CFR 
601.12(d)(3)(ii), licensed establishments implementing these recommendations must submit a 
statement in their annual reports indicating the date that the revised standard operating 
procedures were implemented.  These changes do not require our prior approval. 
12  Contains Nonbinding Recommendations 
IX.  REFERENCES  
 
1.  Possible West Nile Virus Transmission to an Infant Through Breast-FeedingMichigan, 
2002. MMWR Morb Mortal Wkly Rep 2002; 51:877-8. 
2.  http://www.cdc.gov/ncidod/dvbid/westnile/index.htm 
3.  Update: West Nile Virus Screening of Blood Donations and Transfusion-Associated 
Transmission  United States, 2003. MMWR Morb Mortal Wkly Rep 2004; 53:281-284. 
4.  Petersen, L.R., Marfin, A.A. West Nile Virus: A Primer for the Clinician. Ann Intern Med 
2002; 137:173-179.  
5.  http://www.cdc.gov/epo/dphsi/nndsshis.htm   
6.  Blood Products Advisory Committee meeting, October 22, 2004. 
http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004-4074t2.htm 
7.  Kreil, T.R., Berting, A., Kistner, O., Kindermann, J. West Nile Virus and the safety of 
plasma derivatives: verification of high safety margins, and the validity of predictions based 
on model virus data. Transfusion 2003; 43:1023-8. 
8.  Mather, T., Takeda, T., Tassello, J., et al. West Nile Virus in blood: stability, distribution, 
and susceptibility to PEN110 inactivation. Transfusion 2003; 43:1029-37. 
9.  Jakubik, J.J., Vicik, S.M., Tannatt, M.M., Kelley, B.D. West Nile Virus inactivation by the 
solvent/detergent steps of the second and third generation manufacturing processes for B-
domain deleted recombinant factor VIII. Haemophilia 2004; 10:69-74. 
10. Mohr, H., Knuver-Hopf, J., Gravemann, U., et al. West Nile Virus in plasma is highly 
sensitive to methylene blue-light treatment. Transfusion 2004; 44:886-90. 
11. Pealer, L.N., Marfin, A.A., Petersen, L.R., et al. Transmission of West Nile Virus through 
blood transfusion in the United States in 2002. N Engl J Med 2003; 349:1236-45. 
12. Update: Investigations of West Nile Virus Infections in Recipients of Organ Transplantation 
and Blood Transfusion  Michigan, 2002. MMWR Morb Mortal Wkly Rep 2002; 51:879. 
13. Transfusion-Associated Transmission of West Nile Virus  Arizona, 2004. MMWR Morb 
Mortal Wkly Rep 2004; 53:842-844.  
 
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