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
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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 PRODUCTS 11

VIII. IMPLEMENTATION ...................................................................................................12

IX. REFERENCES...............................................................................................................13
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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 Administration’s (FDA’s) 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 
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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 tissuebased products that are subject to 21 Code of Federal Regulations (CFR) Part 1271. 

FDA’s guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the FDA’s 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 FDA’s 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 singlestranded 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 
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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 
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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 FDA’s 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 
Contains Nonbinding Recommendations 

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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). 
Contains Nonbinding Recommendations 

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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 
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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) 
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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.
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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. 
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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 donor’s 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 
Contains Nonbinding Recommendations 

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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 noninjectable products,” whichever is applicable. 
Contains Nonbinding Recommendations 

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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. 
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IX. REFERENCES 

1. Possible West Nile Virus Transmission to an Infant Through Breast-Feeding–Michigan, 

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 Bdomain 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.