Guidance for Industry  

 
Revised Recommendations for the 

Assessment of 
 
Donor Suitability and Blood Product Safety 
 
in Cases of Suspected
  
Severe Acute Respiratory Syndrome 
 
(SARS) or Exposure to SARS

 
 
 FINAL GUIDANCE  

 
This guidance is being distributed for immediate implementation.  
 
FDA is issuing this guidance for immediate implementation in accordance with 21 CFR 
10.115(g)(3).  The agency has determined that seeking comments from the public prior to 
implementation is not appropriate or feasible because there is an immediate need for clarification 
whether FDA recommends that establishments continue to screen donors on the basis of travel to 
SARS-affected areas during time periods when CDC has identified no areas as currently affected 
by SARS.  
 
FDA invites comme nts on this document.  Please submit comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. You should identify all comments with the docket number listed in the 
notice of availability that publishes in the Federal Register.  FDA will review any comments 
received and will revise the guidance document as appropriate.  
 
Additional copies of this guidance are available from the Office of Communication, Training, 
and Manufacturers Assistance (HFM-40), 1401 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  
September 2003 
   
 
 
TABLE OF CONTENTS 
 
 
I.   INTRODUCTION............................................................................................................. 1
  
II.  	 BACKGROUND ............................................................................................................... 2
  
A. 	  Epidemiology and Pathogenesis........................................................................... 2
  
B.	   Definitions .............................................................................................................. 2
  
1.	   CDC Case Definition of Suspected SARS ............................................... 2
  
2.	   Use of CDC Case Definition in Guidance ............................................... 3
  
3.	   Updated Information on Case Definitions and Areas Affected by 

SARS .......................................................................................................... 3
  
4.	   Infection Control Guidelines about SARS.............................................. 4
  
C. 	  Impact of SARS on Blood Safety ......................................................................... 4
  
D.	   Impact of Guidance on Blood Availability ......................................................... 4
  
III. 	  RECOMMENDATIONS.................................................................................................. 5
  
A. 	  Donor Interview Questions .................................................................................. 5
  
B.	   Donor Deferral Actions ........................................................................................ 6
  
C. 	  Post-Donation Information and Lookback Investigation ................................. 6
  
1.	   Product Retrieval and Quarantine .......................................................... 6
  
2.	   Product Disposition and Special Labeling .............................................. 7
  
3.	   Physician Notification about Potential Transfusion-Transmitted 

SARS .......................................................................................................... 7
  
4.	   Notification of State or Local Public Health Departments about 

Suspected Donor Cases of SARS ............................................................. 7
  
IV.   BIOLOGIC PRODUCT DEVIATION AND FATALITY REPORTING .................. 7
  
V.   IMPLEMENTATION ...................................................................................................... 8
  
VI.   REFERENCES .................................................................................................................. 9
  
  i   Contains Nonbinding Recommendations  
Guidance for Industry
  
 
Revised Recommendations for the Assessment of Donor Suitability 

and Blood Product Safety in Cases of Suspected Severe
  
Acute Respiratory Syndrome (SARS) or Exposure to SARS
  
 
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 FDA staff responsible for implementing this guidance.  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 provides our revised recommendations for assessing donor suitability 
and blood product safety with respect to Severe Acute Respiratory Syndrome (SARS).  This 
guidance applies to Whole Blood and blood components intended for transfusion (including red 
blood cells for immunization) and blood components including recovered plasma, Source 
Leukocytes and Source Plasma intended for use in further manufacturing into injectable products 
or non-injectable products.  Within this document, donors refers to all such donors.  The Food 
and Drug Administration (FDA) developed the recommendations in this guidance in consultation 
with other Public Health Service Agencies of the Department of Health and Human Services.  
Within this guidance, you refers to blood establishments, we and our refers to the FDA. 
This guidance does not apply to tissue establishments or to human cells and tissues other than 
blood.  However, tissue establishments may consider implementing similar donor screening 
practices.  This guidance supersedes our previously issued guidance entitled Guidance for 
Industry: Recommendations for the Assessment of Donor Suitability and Blood Product Safety 
in Cases of Suspected Severe Acute Respiratory Syndrome (SARS) or Exposure to SARS dated 
April 2003.   
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency'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 Agency guidances means that something is suggested or 
recomme nded, but not required.  
 
  1
  Contains Nonbinding Recommendations  
II.   BACKGROUND  
 
A.  Epidemiology and Pathogenesis  
 
The Centers for Disease Control and Prevention (CDC) and the World Health Organization 
(WHO) have been investigating a worldwide outbreak of unexplained atypical pneumonia 
referred to as Severe Acute Respiratory Syndrome (SARS).  As of July 2003, over 8,000 
probable cases of SARS have been reported to WHO from 31 countries; in the United States 
as of July 2003, over 300 suspected cases have been reported to CDC from about 30 states.   
Of the United States cases, about 95% had traveled to outbreak areas listed in the case 
definition within 10 days prior to the onset of clinical illness, and the remainder had a history 
of close contact with a person with suspected SARS.  Of these cases reported worldwide, 
approximately 10% (over 800 cases) have been fatal.  In the United States, the majority of 
patients have recovered or stabilized clinically without specific antiviral therapy; no fatalities 
have been reported as of July 2003 (Refs. 1-4 and unpublished CDC communication).  
 
Laboratories at CDC and elsewhere (SARS Laboratory Network organized by WHO) have 
detected a new coronavirus in SARS patients (Refs. 5-9).  Diagnostic tests (nucleic acid and 
serological) for SARS based on the detection of acute infection with the novel coronavirus 
are currently under investigational use.  
 
B.   Definitions  
 
1.	   CDC Case Definition of Suspected SARS  
 
CDCs current interim case definition for a United States case of suspected SARS is 

posted on CDCs website (Ref. 2).  

Respiratory illness which meets the clinical and epidemiologic criteria set forth in CDCs 

websites, such as:  

	   Measured temperature > 100.4 F (>38 C), AND  
	   One or more clinical findings of respiratory illness (e.g., cough, shortness of 
breath, d ifficulty breathing, hypoxia): and radiographic findings of pneumonia or 
respiratory distress syndrome, or autopsy findings consistent with pneumonia or 
respiratory distress syndrome without an identifiable cause), AND  
	   Travel within 10 days of onset of symptoms to an area identified by CDC as a 
SARS-affected area at the time of the donor's travel, OR close contact within 10 
days of onset of symptoms with either a person known or suspected to have 
SARS.  
o	   Please consult CDC for the updated list of SARS -affected areas and current 
SARS definition (see section II.B.3 below for CDC website and phone 
number).  The list and definition are subject to change.  The CDC definition 
currently excludes areas with secondary cases limited to healthcare workers or 
direct house hold contacts.   
o	   Travel includes transit in an airport in an area with documented or suspected 
community transmission of SARS.  
  2
  Contains Nonbinding Recommendations  
o	   Close contact is defined as having cared for, having lived with, or having had 
direct contact with respiratory secretions and/or body fluids of a patient 
known to be a suspect SARS case.  Please consult CDC for the updated case 
definitions, including the definition of close contact (see section II.B.3 below 
for CDC website and phone number).  
 
2. 	  Use of CDC Case Definition in Guidanc e  
 
For donor screening purposes, this guidance currently does not distinguish suspected 
SARS from probable SARS.  The phrase SARS and suspected SARS as used in this 
guidance reflects the current lack of an available approved diagnostic test for SARS.  
 
Although WHO and CDC currently use 10 days as the incubation period in their 
respective case definitions, 14 days may be more appropriate for donor screening as a 
conservative upper limit of the asymptomatic incubation period (time between exposure 
to the SARS agent and the onset of clinical symptoms), based on current available 
information (Ref. 6).  This guidance makes recommendations using 14 days as the 
asymptomatic incubation period.  
 
3. 	  Updated Information on Case Definitions and SARS-Affected Areas  
 
Ep idemiologic and laboratory investigations about SARS are ongoing.  The case 
definitions and the list of SARS -affected areas worldwide are updated periodically as 
new information becomes available.  The case definitions and the updated list of SARS 
affected areas may be obtained at the CDC website or by calling CDC:  
Website:   http://www.cdc.gov/ncidod/sars/casedefinition.htm  
Phone:   888-246-2675; 8 am - 11 pm weekdays, 10 am - 8 pm weekends  
 
Affected areas are defined by evidence of community transmission of SARS.  CDC 
issues a travel advisory upon notification that an outbreak of SARS is occurring in a 
geographic area, and when the risk to a traveler is high because of evidence of 
community transmission and/or inadequate containment. The travel advisory is 
downgraded to a travel alert when there is no evidence of ongoing community 
transmission for 20 days after the date of onset of symptoms for the last case without an 
epidemiological link. CDC removes a travel alert for a geographic area (e.g., country or 
city) if more than 30 days has lapsed since the date of onset of symptoms for the last 
SARS case in that area, and limited or no recent instances of exported cases are reported 
from that area.  As of 15 July 2003, travel alerts for all previously identified SARS- 
affected areas were lifted by CDC, as no areas of the world reported ongoing community 
transmission of disease (www.cdc.gov/ncidod/sars/travel.htm).  It is unknown whether 
outbreaks of SARS will recur or whether exposure to SARS in geographic areas will 
again be included in the SARS case definition.  
  3
  Contains Nonbinding Recommendations  
 
4.   Infection Control Guidelines about SARS  
 
Based on clinical and epidemiological experience to date, CDC has developed interim 
infection control guidelines for use at healthcare and household settings by infection 
control practitioners and clinicians providing medical care for patients with suspected 
SARS, including guidelines for triage of potential SARS cases.  These guidelines are 
available at the CDC websites (Refs. 10-12).  We recommend that blood center personnel 
consult these guidelines frequently to keep abreast of evolving CDC recommendations.  
 
C.  Impact of SARS on Blood Safety  
 
The potential for transmission of SARS through blood and blood products is not known.  The 
possibility of a viremic period, before the onset of clinical symptoms and/or after symptom 
resolution, remains an important concern regarding blood safety.  The new coronavirus that 
is the possible cause of SARS has been isolated from infected kidney, lung, and 
bronchoalveolar-lavage fluid (Ref. 8) but has not been isolated yet from blood or serum of an 
infected individual (Refs. 5-9), though data are limited.  Detection by nucleic acid 
amplification of this new coronavirus in blood samples from persons acutely infected with 
SARS has been reported in a single patient (Ref. 9).  Because, as in some other early viral 
infections, persons with SARS could potentially be viremic without symptoms, transfusion 
transmission of SARS may be possible.  Therefore, until more information is known abo ut 
the epidemiology and pathogenesis of SARS, we recommend, as a preventative measure, the 
implementation of blood donor deferral for at least 14 days after possible exposure to SARS. 
Additionally, in cases of suspected SARS, we recommend donor deferral for at least 28 days 
after symptom resolution and completion of therapy due to the present uncertainty about 
possible persistence of viremia and/or viral shedding in body fluids (Ref. 9).  
 
At this time, we believe SARS is unlikely to be transmitted through products manufactured 
from plasma.  Lipid -enveloped RNA virus(es), including the putative agent(s), should be 
readily removed and/or inactivated during manufacturing of plasma derivatives (Refs. 13, 
14).  Licensed plasma derivatives undergo intentional vir al clearance procedures that are 
validated to be effective against lipid-enveloped RNA viruses.  These procedures include: 
filtration, heating, acidification, and detergent treatment.  Based on any new scientific 
information about the safety of plasma derivatives, we intend to revise these 
recommendations as appropriate.  
 
D.  Impact of Guidance on Blood Availability  
 
Our recommendations contained in this revised guidance reflect recent active consultation 
with CDC.  The impact of this guidance on any possible future outbreaks of SARS will vary 
depending on the geographic areas affected by SARS and thus cannot be predicted.  We will 
monitor closely the impact of this guidance on the blood supply.  Based on that impact 
assessment and any new scientific information about the potential risk of transfusion 
transmission of the infectious agent(s) causing SARS, we intend to revise these 
recommendations as appropriate.  
  4
  Contains Nonbinding Recommendations  
 
 
III.   RECOMMENDATIONS 
 
 
Consistent with existing regulations and applicable guidance, donors must be in good health at 
the time of donation [21 CFR 640.3(b) and 21 CFR 640.63(b)(3)].  Standard procedures that are 
already in place should serve as an effective safeguard against the unusual donor who seeks to 
donate after the onset of clinical illness.  The following recommendations apply primarily to the 
potentially infected person during the asymptomatic incubation period before the onset of 
clinical symptoms.  
 
A.  Donor Interview Questions  
 
To ensure that the questions used remain consistent with updated case definitions and the list 
of SARS-affected areas, we recommend that you routinely and periodically refer to the CDC 
website (www.cdc.gov/ncidod/sars/casedefinition.htm) or call CDC (888-246-2675; 8 am   
11 pm weekdays, 10 am - 8 pm weekends) to obtain t he updated information.  
 
At donor interview, in the event that CDC has identified SARS -affected areas as existing 
within the previous 90 days, we recommend that you ask (orally or in writing) potential 
donors about:  
 
1. 	History of SARS, suspected SARS, or treatment for SARS within the previous 28 
days.  For example, In the past 28 days, have you been ill with SARS or suspected 
SARS?  
 
2. 	 Close contact within the previous 14 days with persons with SARS or suspected 
SARS.  For example,  In the past 14 days, have you cared for, lived with, or had 
direct contact with body fluids of a person with SARS or suspected SARS?  
 
Ninety days after CDC has lifted all travel alerts for SARS -affected areas, we recommend 
that you discontinue asking donors questions 1) and 2).  
 
At donor interview, in the event that CDC has identified SARS -affected areas as existing 
within the previous 14 days, we recommend that you ask (orally or in writing) potential 
donors about:  
 
3. 	 Travel to or residence in SARS -affected areas within the previous 14 days.  Blood 
collection establishments with existing capture questions (e.g., Have you traveled 
outside the United States within the past year?) should review these questions to 
ensure that they are adequate to identify possible travel to CDC defined SARS 
affected areas.  Capture questions may be followed up with questions specific to travel 
to SARS -affected areas as necessary.   
 
If adequate travel capture questions are not currently in use, we recommend that 
donors be asked a specific q uestion about travel or residence in SARS -affected areas 
  5
  Contains Nonbinding Recommendations  
within the past 14 days.  For example, In the past 14 days, have you traveled to, 
traveled through, or resided in areas affected by SARS?  
 
Note that you should read to or show donors a list of SARS -affected areas as updated 
by CDC.  
 
Fourteen days after CDC has lifted the travel alert for a geographic area, we 
recommend that you discontinue asking donors question 3) concerning travel or 
residence in that area related to SARS.   
 
B.   Donor Deferral Actions  
 
We recommend that donors reporting a history of SARS or suspected SARS be asked about 
duration of symptoms and any treatment given.  We recommend that you defer these donors 
for a period of at least 28 days after complete symptom resolution AND the cessation of any 
treatment.  
 
For asymptomatic donors with a history of contact with persons with SARS or suspected 
SARS, we recommend that you defer these donors for a period of at least 14 days after last 
exposure.  For travel/residence exposure, the do nor should be deferred for at least 14 days 
after arrival in the United States.  
 
C.   Post-Donation Information and Lookback Investigation  
 
We recommend that you actively encourage donors to report, post donation, any further 
information about SARS exposure that may have occurred within 14 days prior to donation, 
or SARS illness or treatment within 28 days prior to donation.  Donors should also be 
encouraged to report SARS illness or treatment that occurs within 14 days after donation. 
These recommendations o n post-donation information and lookback investigation apply to 
Whole Blood and blood components intended for transfusion (including red blood cells for 
donor immunization), and to unpooled units of recovered plasma, Source Plasma, and Source 
Leukocytes, b ut not to pooled units of plasma.  
 
1.   Product Retrieval and Quarantine  
 
If a donor reports, post donation, a history of SARS disease (as described in section 
III.A.1, above) that occurred within 28 days prior to blood collection, SARS exposure (as 
described in sections III.A.2 and III.A.3, above) that occurred within 14 days prior to 
blood collection, or SARS disease that occurred within 14 days after blood collection, we 
recommend that blood establishments promptly retrieve and/or quarantine the collected 
in-date units of Whole Blood and/or blood components and any unpooled units collected 
for further manufacturing.  
NOTE:  If the donor is symptom-free more than 14 days post-exposure, product retrieval 
and quarantine are not necessary.   
 
  6
  Contains Nonbinding Recommendations  
2.   Product Disposition and Special Labeling  
 
Quarantined units should be destroyed in accordance with established procedures, unless 
distributed for further manufacturing into non-injectable products or for research use 
under special labeling, as follows:  
 
Biohazard, AND  

Collected from a donor with SARS exposure or suspected SARS,  

 
AND 
 
 
For laboratory research use only, OR  

Intended only for further manufacturing into non-injectable products. 
 
 
3.   Physician Notification about Potential Transfusion-Transmitted SARS  
 
A blood establishment (including a blood collecting establishment or transfusion service) 
may receive information that a donor of already-transfused blood or blood components 
has been exposed to SARS, or became sick with suspected SARS, during the time frames  
described in section III.A.1-3.  We recommend that the establishments consider notifying 
the treating physician of the recipients of the suspect unit(s) about the post donation 
information, including whether the donor developed suspected SARS.   
 
4. Notification of State or Local Public Health Departments about Suspected Donor 
Cases of SARS  
 
We recommend that blood establishments report cases of SARS in either donors or blood 
recipients to their respective state or local public health departments.  Also, if a donor 
reports the existence of clinical symptoms consistent with SARS within 14 days 
subsequent to donation, and a possible SARS exposure, CDC has asked blood 
establishments to contact the CDCs Assistant Director for Blood Safety, Office of the 
Director, Division of Viral and Rickettsial Diseases (404-639-2775) to determine if 
retrieved units should be sent to CDC for laboratory studies, under quarantine and 
specially labeled as indicated above.   
 
 
IV.   BIOLOGIC PRODUCT DEVIATION AND FATAL ITY REPORTIN G  
 
Regulations on reporting of product deviations by licensed manufacturers, unlicensed registered 
blood establishments, and transfusion services are located at 21 CFR 606.171 and 21 CFR 
600.14.  Pursuant to these regulations, blood and plasma collection establishments (including 
establishments that collect Source Leukocytes and licensed manufacturers of leukocyte 
derivatives) must submit biological product deviation reports for events related to SARS, if the 
establishment distributed the affected product.  Additionally, if a suspect donation results in the 
fatality of a transfusion recipient, blood establishments must report the fatality to the FDA [21 
CFR 606.170(b)].  
  7
  Contains Nonbinding Recommendations  
 
 
V.   IMPLEMENTATION  
 
We recommend that you implement the recommendations in this guidance as soon as feasible, 
but not later than 30 days after the guidance issue date.  Consistent with 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 establishment revised and 
implemented their standard operating procedures, consistent with these recommendations.  These 
changes do not require our prior approval.  
  8
  Contains Nonbinding Recommendations  
VI.   REFERENCES  
 
1. 	  Centers for Disease Control and Prevention.  Outbreak of Severe Acute Respiratory 
Syndrome -- worldwide, 2003.  MMWR 2003; 52:226-228.  
2. 	  Centers for Disease Control and Prevention.  Severe Acute Respiratory Syndrome (SARS) 
updated interim case definition.  http://www.cdc.gov/ncidod/sars/casedefinition.htm.  
3.	   World Health Organization.  Cumulative number of reported cases of Severe Acute 
Respiratory Syndrome (SARS).  http://www.who.int/csr/sarscountry/2003_04_02/en.  
4.	   World Health Organization.  Case definitions for surveillance of Severe Acute Respiratory 
Syndrome (SARS).  http://www.who.int/csr/sars/casedefinition/en.  
5. 	  Tsang KW, Ho PL, Ooi GC, et al.  A cluster of cases of Severe Acute Respiratory Syndrome 
in Hong Kong.  New England Journal of Medicine (on-line). 
http://content.nejm.org/cgi/content/abstract/NEJMoa030666v1 .  
6. 	  Lee N, Hui D, Wu A, et al.  A major outbreak of Severe Acute Respiratory Syndrome in 
Hong Kong.  New England Journal of Medicine (on-line). 
http://nejm.org/earlyrelease/sars.asp.  
7. 	  Poutanen SM, Low DE, Henry B, et al.  Identification of Severe Acute Respiratory 
Syndrome in Canada.  New England Journal of Medicine (on-line). 
http://nejm.org/earlyrelease/sars.asp.  
8. 	  Ksiazek TG, Erdman D, Goldsmith C, et al.  A novel coronavirus associated with Severe 
Acute Respiratory Syndrome.  New England Journal of Medicine (on-line). 
http://nejm.org/earlyrelease/sars.asp.  
9. 	  Drosten C, Guenther S, Preiser W, et al.  Identification of a novel coronavirus in Patients 
with Severe Acute Respiratory Syndrome.  New England Journal of Medicine (on-line). 
http://nejm.org/earlyrelease/sars.asp.  
10.  Centers for Disease Control and Prevention. 	 Interim guidance on infection control 
precautions for patients with suspected Severe Acute Respiratory Syndrome (SARS) and 
close contacts in households.  http://www.cdc.gov/ncidod/sars/ic -closecontacts.htm.  
11.  Centers for Disease Control and Prevention. 	 Triage of Patients Who May Have Severe 
Acute Respiratory Syndrome: Interim Guidance for Screening in Ambulatory Care Settings. 
http://www.cdc.gov/ncidod/sars/triage_interim_guidance.htm.  
 
12.  Bartlett JG, Dowell SF, Mandell LA, et al. 	 Practice guidelines for the management of 
community-acquired pneumonia in ad ults.  Clinical Infectious Disease 2000; 31:347-382.  
 
13.  Lamarre A and Talbot PJ. 	 Effect of pH and temperature on the infectivity of human 
coronavirus 229E.  Canadian Journal of Microbiology 1989; 35:972-974.  
 
14.  Bucknall RA, King LM, Kapikian AZ, et al.  S	 tudies with human coronaviruses. II. Some 
properties of strains 229E and OC43.  Proceedings of the Society of Experimental Biology 
and Medicine 1972; 139:722-727.  
 
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