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

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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
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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.
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
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.
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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
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, 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.
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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 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.
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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 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.
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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
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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.
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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 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 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)].
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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.
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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 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. 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.
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