Guidance for Industry 

Recommendations for Assessment of
 
Donor Suitability and Blood and Blood
 
Product Safety in Cases of Possible
 
Exposure to Anthrax
 
Final Guidance 
This guidance is being distributed for immediate implementation. 
FDA is issuing this guidance without initially seeking comment because the agency has 
determined that prior public participation is not feasible or appropriate.  Comments and 
suggestions regarding this document should be submitted anytime to Dockets Management 
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 
20852.  All comments should be identified with the docket number listed in the notice of 
availability that publishes in the Federal Register. 
Additional copies of this guidance are available from the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), 1401 Rockville Pike, 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 (CBER) 
October 2001  TABLE OF CONTENTS 

I.  INTRODUCTION............................................................................................................. 1
 
II.  BACKGROUND ............................................................................................................... 1
 
III.  RECOMMENDATIONS on DONOR DEFERRAL...................................................... 4
 
A.  Proven Anthrax Disease of Any Type or Proven Bacterial Colonization................ 4
 
B.  Undiagnosed Skin Lesions Suspected to be Anthrax ................................................. 4
 
IV.  RECOMMENDTIONS on PRODUCT QUARANTINE AND RETRIEVAL ............ 5
 
A.  Proven Anthrax Disease of Any Type ......................................................................... 5
 
B.  Undiagnosed Post-donation Illness in Potentially Exposed Individuals .................. 5
 
V. 	 RECOMMENDATIONS on NOTIFICATION OF PRIOR TRANSFUSION 

RECIPIENTS .................................................................................................................... 5
 
VI. 	 IMPLEMENTATION....................................................................................................... 6
 
VII. 	 REFERENCES .................................................................................................................. 6
 
APPENDIX:  SIGNS AND SYMPTOMS OF ANTHRAX INFECTION1 .............................. 7
 
i  GUIDANCE FOR INDUSTRY 
Recommendations for Assessment of Donor Suitability and Blood 
and Blood Product Safety in Cases of Possible Exposure to Anthrax 
This guidance document represents the agencys 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. 
An alternative approach may be used if such approach satisfies the requirements of the 
applicable statute and regulations. 
I.   INTRODUCTION 
This guidance document provides the current recommendations of the Food and Drug 
Administration (FDA) for assessment of donor suitability and product safety for donors 
potentially exposed to Bacillus anthracis, the agent of anthrax.  This guidance applies to Whole 
Blood, blood components (including recovered plasma) and Source Plasma collections intended 
for use in transfusion or for further manufacturing into injectable products.  FDA developed the 
recommendations in this guidance in consultation with other Public Health Service Agencies and 
with the Blood Safety Committee of the Department of Health and Human Services. 
At present there are insufficient systematic human data to fully address the possible occurrence 
of bacteremia in an asymptomatic individual who is infected with anthrax bacilli.  However, 
based on the current available scientific data, highly knowledgeable experts agree that such a 
possibility is extremely remote.  There is no known risk of transmission of anthrax from blood 
collected from asymptomatic donors who might have been exposed to the anthrax bacterium. 
Moreover, current regulations provide for the deferral of any donor who is not in good health at 
the time of donation, and specifically require deferral of a donor with acute respiratory disease or 
any infectious skin disease presenting a risk of contamination of the blood.  [21 CFR 640.3(b) 
and 21 CFR 640.63(c)]  Nevertheless, FDA is issuing guidance on prudent measures that should 
be taken to reduce any possible risk for transmission of anthrax from blood or blood products. 
II.   BACKGROUND 
Anthrax is caused by the bacterium Bacillus anthracis, a spore forming Gram-positive rod. 
Anthrax spores can tolerate dry conditions and stay intact for long periods of time (years), 
especially if they are shielded from UV light exposure.  When the spores are inoculated, 
ingested, or inhaled they germinate to the bacterial (vegetative) form that multiply rapidly and 
invade tissues.  There are three types of anthrax infection in humans: cutaneous, gastrointestinal, 
and inhalational. 
Anthrax is reported annually among livestock in the United States.  In areas where these animal 
cases occur, most human cases are the cutaneous form.  Such cases occur among workers who 
have handled infected hoofed animals, or products from these animals.  Gastrointestinal anthrax 
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  has been reported following the ingestion of undercooked or raw meat from infected animals. 
Inhalational anthrax, resulting from inhalation of aerosolized spores, was associated with 
industrial processing of infected wool, hair or hides in the United States in the past.  Prior to 
October 2001, no case of inhalational anthrax had been reported in the United States since 1978. 
Cutaneous anthrax has an incubation period that ranges from 1 to 12 days. The skin lesions of 
cutaneous anthrax typically are found on the hands, arms or feet.  The early infection is 
localized, appearing first as a papule that progresses over a few days to a 1-2 cm. vesicle that 
ruptures leaving a black, necrotic ulcer.  The cutaneous infections usually can be cured with 
antibiotics. 
Gastrointestinal anthrax is considered to have an incubation period that ranges from 1 to 7 days. 
Gastrointestinal anthrax includes anthrax of the mouth and throat (oropharyngeal) and anthrax 
of the lower gastrointestinal tract (abdominal).  Involvement of the oropharynx is characterized 
by lesions at the base of the tongue, sore throat, dysphagia, fever, and regional 
lymphadenopathy.  Lower gastrointestinal tract involvement usually causes nausea, loss of 
appetite, vomiting and fever, followed by abdominal pain, vomiting blood, and the occurrence of 
bloody diarrhea. 
The most serious form of anthrax occurs when someone inhales spores (inhalational anthrax), 
leading to a fulminant infection in the chest (necrotizing mediastinitis) and septicemia.  This 
disease is rapidly fatal in almost all cases unless therapy is begun before the disease becomes 
advanced. The incubation period of inhalational anthrax among humans is unclear, but it is 
reported to between 1 and 7 days, and possibly sometimes as long as 60 days. 
While ciprofloxacin, doxycycline and penicillin are the antibiotics most often recommended by 
infectious diseases experts and public health authorities, susceptibility testing is critical in 
guiding antibiotic therapy for anthrax, particularly for treating presumed intentional infections. 
Clinicians should consult the Centers for Disease Control and Prevention (CDC) or local public 
health authorities for further guidance. 
 
Standard infection control precautions (handwashing, wearing gloves for handling contaminated 
materials) are sufficient when treating patients with anthrax.  Inhalational anthrax is not 
contagious from person to person, obviating a need for respiratory precautions.  Bacillus 
anthracis is very resistant to common environmental conditions that would destroy non-spore
forming organisms.  However, household bleach, diluted 1:10 and applied for 30 minutes will 
eliminate the spore form as well as the bacterial form of B. anthracis. Steam sterilization, 
autoclaving, or burning may also be employed for destruction of the spores and bacteria. 
Limited amounts of a vaccine for anthrax have been produced but are not currently available for 
general use. 
Blood Donor and Blood Product Issues 
The FDA has received inquiries about procedures for blood collection in reaction to reports of 
exposures to B. anthracis.  To date, these reports have involved small numbers of persons either 
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  with anthrax infection (disease) or well individuals from whom the anthrax bacillus could be 
cultured or otherwise detected (colonization).  In these cases, anthrax apparently was acquired in 
circumscribed locations after direct contact with contaminated materials. Inquiries have focused 
on the safety of blood donation by other individuals living or working in the same general area 
who might also have been exposed.  In response, FDA is issuing guidance on prudent measures 
that should be taken to reduce any possible risk for transmission of anthrax from blood or blood 
products. 
In most cases of cutaneous anthrax, the bacteria are localized at the site of inoculation of the skin 
where they cause development of a necrotic ulcer.  The organisms usually do not enter the 
bloodstream unless the individual remains untreated.  Although clinical experience with 
gastrointestinal anthrax is extremely limited, bacteremia is known to occur in the fulminant stage 
of the abdominal form of gastrointestinal anthrax.  In inhalational anthrax, the bacteria initially 
are localized to the mediastinal lymph nodes.  After a generally brief incubation period, a 
fulminant illness develops that is characterized by necrotizing mediastinitis and bacterial sepsis. 
The appearance of anthrax bacteria in the blood of an infected person is thought to coincide very 
closely with the onset of fever and other symptoms of a serious illness in any form of anthrax. 
Thus,  the likelihood of anthrax bacteremia in a person who feels well enough to donate is 
extremely remote.  For this reason, standard screening procedures that exclude sick persons from 
donating blood are expected to result in deferral of donors who otherwise might transmit the 
disease due to bacteria in their blood.  In addition, the apparently limited number of individuals 
exposed in these recent episodes makes transfusion transmission of anthrax even less likely to 
occur. 
After consulting with scientific experts at the CDC, the National Institutes for Health (NIH), and 
the United States Army Medical Research Institute for Infectious Diseases (USAMRIID) about 
the possible transmission of anthrax by blood transfusion, the FDA is not recommending any 
changes to standard donor screening and blood collection procedures to identify or otherwise 
query donors who may have been exposed to anthrax.  This policy is based on the assessment 
that there is not known or suspected to be a significant risk of transmission of anthrax from blood 
collected from asymptomatic donors who might have been exposed to the anthrax bacterium or 
its spores, and the fact that standard blood collection procedures that already are in place include 
deferral of any donor who is not in good health at the time of donation. 
If an asymptomatic donor (other than those donors known to have proven bacterial colonization) 
mentions use of antibiotics to prevent anthrax, medical directors may exercise their own 
discretion whether to defer donors who are taking antibiotics.  If an otherwise healthy and 
asymptomatic potential donor is taking antibiotics solely because medical or public health 
authorities recommended this after possible exposure to anthrax, donation is acceptable if all 
other criteria are met. 
Nevertheless, as a prudent measure to address the possible increased risk of anthrax bacteremia 
in cases of active disease or proven bacterial colonization (as opposed solely to potential 
exposure), FDA  is providing recommendations on criteria for donor deferral, and on criteria for 
product quarantine and retrieval related to reports of post-donation illnesses. 
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  The FDA is continuing to consult with experts on anthrax at the CDC, NIH, and USAMRIID to 
ensure the greatest possible safety of the blood supply.  In addition, the situation and 
epidemiology of this and other potential biological threats are rapidly changing. Any new data or 
experience related to this issue will be evaluated rapidly and further updates will be provided as 
appropriate. 
III.   RECOMMENDATIONS ON DONOR DEFERRAL 
Consistent with existing regulations and applicable guidance, donors should be in good health 
and free of acute respiratory illnesses and of infectious skin disease presenting a risk of 
contamination of the blood. [21 CFR 640.3(b) and 21 CFR 640.63(c)] Standard procedures that 
already are in place should be adequate to defer potential donors who may have gastrointestinal 
or inhalational anthrax at the time of donation since such persons are expected to be 
symptomatic.  However, additional considerations are needed to address bacterial colonization in 
an asymptomatic donor.  Also, special consideration is needed to address confirmed or suspected 
cutaneous anthrax because the skin lesions usually are painless.  At this time, FDA is not 
proposing revisions to standard donor questions.  However, a donor may report such lesions, or 
in the performance of routine donor screening and preparation for phlebotomy, a skin lesion 
compatible with cutaneous anthrax may be found. 
The following recommendations apply to cases of known or suspected anthrax disease or proven 
bacterial colonization at the time of donation. 
A.   Proven Anthrax Disease of Any Type or Proven Bacterial Colonization 
1. 	 FDA recommends that a potential donor with a current confirmed medical diagnosis of 
anthrax of any form should be deferred until the person subsequently completes a full 
course of an appropriate treatment and the condition is considered to be resolved. 
2. 	 Although there is no evidence that proven bacterial colonization in well persons indicates 
an increased risk for transmission of anthrax by transfusion, as a prudent measure FDA 
recommends that such persons should be deferred from donation until they have 
completed a full course of prophylaxis with an appropriate antibiotic. 
B.   Undiagnosed Skin Lesions Suspected to be Anthrax 
FDA recommends that a potential donor with a skin lesion suspected to be anthrax should be 
deferred until either: 
a) 	 the lesion is later shown not to be due to anthrax (and is not otherwise considered to be a 
cause for deferral), or 
b)  the lesion is confirmed as cutaneous anthrax and the person subsequently completes a full 
course of an appropriate treatment and the infection is considered to be resolved. 
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  IV.   RECOMMENDTIONS ON PRODUCT QUARANTINE AND RETRIEVAL 
The FDA is recommending that blood establishments quarantine and retrieve previously 
collected in-date units of blood and blood components intended for transfusion, as well as 
unpooled units of Source Plasma and recovered plasma intended for fractionation to make 
injectable products under the following circumstances: 
A.   Proven Anthrax Disease of Any Type 
FDA recommends that the in-date blood components from prior collections should be 
quarantined and retrieved promptly if a donor later reports a confirmed medical diagnosis of 
anthrax (i.e., clinical disease of anthrax and not solely bacterial colonization).  Product 
quarantine and retrieval should date back to the known time of potential donor exposure to B. 
anthracis or 60 days prior to the onset of illness, whichever is the shorter period. 
B.   Undiagnosed Post-donation Illness in Potentially Exposed Individuals 
In cases of undiagnosed post-donation illnesses among donors who were in areas under 
investigation for anthrax exposures, FDA recommends that medical directors should exercise 
judgment regarding product quarantine and retrieval.  Factors that may be considered include 
the character and severity of the illness (index of suspicion for anthrax), the likelihood of 
anthrax exposure for the specific individual, and whether or not the donor subsequent to an 
anthrax exposure received an appropriate course of antibiotic therapy recommended by 
public health authorities as effective prophylaxis against anthrax in the setting of likely 
exposure to the anthrax bacterium. In general, quarantine and retrieval would not be expected 
in response to undiagnosed illnesses unless there were felt to be strong epidemiologic and/or 
clinical evidence raising the suspicion of active anthrax disease. 
If a decision is made to quarantine and retrieve prior collections, then product quarantine and 
retrieval should be performed promptly and should date back to the known time of potential 
donor exposure to anthrax or 60 days prior to the onset of illness, whichever is the shorter 
period. 
V.   RECOMMENDATIONS ON NOTIFICATION OF PRIOR TRANSFUSION 
RECIPIENTS 
In the case that subsequent to donation, a donor is reported to have a confirmed medical 
diagnosis of anthrax (clinical disease of anthrax and not solely bacterial colonization), FDA 
recommends that medical directors consider the need for prompt record tracing and notification 
to the treating physicians of prior recipients of blood and blood components collected from that 
donor.  FDA considers relevant units to be those dating back to the known time of potential 
donor exposure to anthrax, or 60 days from onset of illness, whichever is the shorter period. 
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Because the chance of anthrax transmission from transfusion is highly unlikely, FDA is not 
recommending lookback notification of blood and blood component recipients in cases of prior 
donation by a person who later reports an undiagnosed illness compatible with anthrax.  
 
 
VI.   IMPLEMENTATION  
 
The recommendations in this guidance should be implemented immediately and do not require 
prior approval from the FDA.  Under 21 CFR 601.12 licensed establishments implementing 
these recommendations should submit by official correspondence a statement in their annual 
reports indicating the date that the revised standard operating procedures, consistent with these 
recommendations have been established and implemented.  
 
 
VII.   REFERENCES  
 
1. 	  A.M. Friedlander, Anthrax, In: F.R. Sidell, E.T. Takafuj i, D.R. Franz, eds. Textbook of   
      Military Medicine: Medical Aspects of Chemical and Biological Warfare, Washington, DC:  
      Office of the Surgeon General, Dept. of the Army, 1997, 467-478.  
 
2. 	  T.V. Inglesby, D.A. Henderson, J.G. Bartlett, M.S. Ascher, E. Eitzen, A.M. Friedlander, J. 
Hauer, J. McDade, M.T. Osterholm, T. OToole, G. Parker, T.M. Perl, P.K. Russel, K. Tonat, 
Anthrax as a Biological Weapon; Medical and Public Health Management, JAMA (1999) 
281; 1735-1745.  
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   APPENDIX:  SIGNS AND SYMPTOMS OF ANTHRAX INFECTION1 
Inhalational anthrax:  A brief prodrome resembling a viral respiratory illness followed by 
development of hypoxia and dyspnea, with radiographic evidence of mediastinal widening. 
This, the most lethal, form of anthrax results from inspiration of 8,000-40,000 spores of B. 
anthracis. The incubation of inhalational anthrax among humans is unclear, but it is reported to 
range between 1 and 7 days possibly ranging up to 60 days.  Host factors, dose of exposure and 
chemoprophylaxis may play a role. Initial symptoms include sore throat, mild fever, muscle 
aches and malaise. These may progress to respiratory failure and shock. Meningitis frequently 
develops. Case-fatality estimates for inhalational anthrax are based on incomplete information 
regarding exposed populations and infected populations in the few case series and studies that 
have been published. However, case-fatality is extremely high, even with all possible supportive 
care including appropriate antibiotics. Records of industrially acquired inhalational anthrax in the 
United Kingdom before antibiotics were available reveal that 97% of cases were fatal.  With 
antibiotic treatment the fatality rate is estimated to be at least 75%.  Estimates of the impact of 
the delay in post-exposure prophylaxis or treatment on survival are not known.  It has been 
suggested that each day of delay in initiating treatment may significantly increase morbidity and 
mortality from anthrax infection. 
Gastrointestinal anthrax:  Severe abdominal distress followed by fever and signs of septicemia. 
This form of anthrax usually follows the consumption of raw or undercooked contaminated meat 
and is considered to have an incubation period of 1-7 days. An oropharyngeal and an abdominal 
form of the disease have been described in this category. Involvement of the pharynx is usually 
characterized by lesions at the base of the tongue, sore throat, dysphagia, fever, and regional 
lymphadenopathy. Lower bowel inflammation usually causes nausea, loss of appetite, vomiting 
and fever, followed by abdominal pain, vomiting blood, and bloody diarrhea. The case-fatality 
rate is estimated to be 25-60%, and the effect of early antibiotic treatment on that case-fatality 
rate is not defined. 
Cutaneous anthrax:  A skin lesion evolving from a papule, through a vesicular stage, to a 
depressed black eschar.  This is the most common naturally occurring type of infection (>95%) 
and usually occurs after skin contact with contaminated meat, wool, hides, or leather from 
infected animals.  Incubation period ranges from 1-12 days. Skin infection begins as a small 
papule, progresses to a vesicle in 1-2 days followed by a necrotic ulcer.  The lesion is usually 
painless, but patients also may have fever, malaise, headache and regional lymphadenopathy. 
The case-fatality rate for cutaneous anthrax is 20% without, and less than 1% with, antibiotic 
treatment. 
1See CDC Guidelines for State Health Departments, Revised October 14, 2001. 
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