 |
 |
 |
|
 |
FDA Home Page | CBER A-Z Index | CBER Search | Contact CBER | CBER Home Page  |
||||
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.
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.
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:
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.
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 SARS-affected areas may be obtained at the CDC website or by calling CDC:
Website: http://www.cdc.gov/ncidod/sars/casedefinition.htm
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.
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.
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 viral 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.
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.
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.
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:
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:
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.
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.
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.
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
AND
"For laboratory research use only," OR
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.
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.
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)].
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.
|
