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 comments 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
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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
Contains Nonbinding Recommendations

1

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 

recommended, but not required.
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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

CDC’s current interim case definition for a United States case of suspected SARS is 

posted on CDC’s website (Ref. 2). 

Respiratory illness which meets the clinical and epidemiologic criteria set forth in CDC’s 

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, difficulty 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 household contacts. 

o Travel includes transit in an airport in an area with documented or suspected 

community transmission of SARS.
Contains Nonbinding Recommendations

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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 Guidance

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

Epidemiologic 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 SARSaffected 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 SARSaffected 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.
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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 about 

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.
Contains Nonbinding Recommendations

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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 the 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 SARSaffected 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 question about travel or residence in SARS-affected areas 
Contains Nonbinding Recommendations

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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 donor 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 on 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, but 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. 
Contains Nonbinding Recommendations

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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 CDC’s 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 FATALITY REPORTING

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)].
Contains Nonbinding Recommendations

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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.
Contains Nonbinding Recommendations

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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 adults. 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. Studies with human coronaviruses. II. Some 

properties of strains 229E and OC43. Proceedings of the Society of Experimental Biology 

and Medicine 1972; 139:722-727.