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FDA is responsible for ensuring the safety of the Nation’s blood supply. While a blood supply with zero risk of transmitting infectious disease may not be possible, there are several measures taken by FDA to protect and enhance the safety of blood products.
The blood safety system established by FDA is dependent upon: 1) accurate and complete educational material for donors so that they can assess their risk; 2) sensitive communication of the donor screening questions; 3) donor understanding and honesty; 4) quality controlled infectious marker testing procedures; and 5) appropriate handling and distribution of blood and blood products for patient use. Because of the improvements in donor screening procedures and the use of a variety of new tests in the last few years, the blood supply is safer from infectious diseases than it has been at any other time.
A person’s suitability to donate blood depends on two general considerations: that the donation will not be injurious to the donor, and that the donated blood will not be unnecessarily hazardous to the recipient. Regulations enforced by FDA require that as part of the suitability criteria, a donor be free from any disease transmissible by blood transfusion, in so far as can be determined by health history and medical examination.
Keeping Blood Transfusions Safe; FDA's Multi-layered Protections for Donated Blood
Why are good donors being deferred because they have visited the U.K.?
Regulations enforced by FDA require that as part of the suitability criteria, a donor be free from any disease transmissible by blood transfusion, in so far as can be determined by health history and medical examination.
FDA periodically issues guidance providing recommendations to decrease the potential for transmission of infectious disease when new information or testing methodology becomes available. In August, 1999, FDA issued guidance for Industry entitled, "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfedlt-Jakob Disease (CJD) and New Variant Creutzfeldt-Jakob Disease (nvCJD) by Blood and Blood Products". After reviewing the comments received, FDA further revised the guidance on November 23, 1999. A copy of the most recent revised guidance is available at http://www.fda.gov/cber/gdlns/cjdvcjd.pdf.
The guidance states that, "FDA believes that donors who have resided in the United Kingdom (as identified by questions in section III.D) may be at risk for exposure to nvCJD. As a precaution, FDA recommends that donors who have spent six months or more cumulatively in the United Kingdom from 1980 through 1996 (i.e., from January 1, 1980 through December 31, 1996) be indefinitely deferred."
FDA takes a conservative approach to ensure the safety of the Nation’s blood supply and therefore, issues guidance relating to both known infectious diseases as well as potentially emerging diseases. This conservative approach may result in the deferral of otherwise acceptable donors.
FDA recognizes that the scientific technology for determining individuals at risk for CJD and nvCJD, and detecting the infectious agents in tissues and in products, is continuing to advance, and that there may be a need for future updating of the relevant guidance.
How many people have died as a result of nvCJD?
Cases of variant CJD are very rare, and most have occurred in the United Kingdom. The latest information (October 2, 2000) issued by the Department of Health, United Kingdom (www.doh.gov.uk/cjd/) indicates that there have been 73 confirmed cases of vCJD in the United Kingdom. These cases have all been diagnosed since 1995. France has reported two cases. The Republic of Ireland reported one case in 1999. No cases have been recognized in other European countries, or in the United States.
Where can I obtain more epidemiological information or statistics regarding nvCJD?
Please check CBER's web site at:
Bovine Spongiform Encephalopathy (BSE)
Further information about the disease can be obtained from the Centers for Disease Control and Prevention (CDC):
Centers for Disease Control and Prevention
1600 Clifton Road
Atlanta, Georgia 30333
Phone: 404-639-3091
Website: http://www.cdc.gov/
Where can I obtain additional information issued by the FDA regarding nvCJD?
Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products - 1/9/2002 -
(PDF),
(Text)
Revised Guidance: "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) by Blood and Blood Products" - Information Sheet - 9/8/98
TSE Advisory Committee 6/2/99 Transcript
TSE Advisory Committee 6/3/99 Transcript
Is it true that individuals diagnosed with hemochromatosis can now donate?
FDA has always allowed individuals diagnosed with hemochromatosis to donate blood. However, FDA is now allowing variances to the requirements that blood establishments 1) label such blood with the donor’s disorder, and 2) have a physician examine the donor at the time of donation if less than eight weeks has passed since the previous donation. These variances are specific for individuals with hereditary hemochromatosis.
The existing regulations require that blood establishments using blood collected during therapeutic bleedings label these units with the disease that necessitated the therapeutic bleeding (21 CFR Part 640.3 (d)) and limit the frequency of whole blood collections (21 CFR Part 640.3 (f)). The CFR sections are availble at: http://www.access.gpo.gov/nara/cfr/waisidx_03/21cfr640_03.html. FDA has the authority to permit exemptions to the blood regulations under the provisions of 21 CFR 640.120, Alternative Procedures.
In August 2001, FDA issued Guidance for Industry: Variances for Blood Collection from Individuals with Hereditary Hemochromatosis providing recommendations to blood establishments that wish to apply for these variances. Refer to the guidance document for the conditions blood establishments must meet in order for us to approve the variance requests.
Not all blood establishments have applied for these variances. Ultimately, it is the decision of each blood establishment to apply for any variance. A list of the facilities that have been granted the hemochromatosis-related variances is available at http://www.fda.gov/cber/blood/hemochromvar.htm.
In summary, when a blood establishment desires to use blood from a therapeutic hemochromatosis bleeding for transfusion purposes, the blood establishment must either 1) label the collected blood with the donor’s disorder and have a physician examine the donor on the day of donation if less than eight weeks has passed since the previous donation, or 2) apply for the variances.
I was diagnosed with hepatitis at a young age. Am I still deferred?
Under Title 21 CFR 610.41, persons with a history of a positive (confirmed) test for hepatitis B virus surface antigen (HBsAg), regardless of age at the time of the positive test, may not serve as a donor of human blood, plasma, or serum.
Donor suitability in regard to a history of viral hepatitis at the age of 11 years or later should be assessed by asking the donor for recollections of experiencing physical signs or symptoms of clinical hepatitis (e.g., "yellow jaundice," or other pertinent physical evidence of clinical hepatitis), or having received a diagnosis of viral hepatitis from a physician. Records of laboratory data (e.g., serology, ALT, AST, bilirubin, prothrombin time), if available, may assist the medical director in making the donor suitability determination in the face of an inconclusive history. However, certain isolated laboratory test results should not be considered equivalent to a history of viral hepatitis. In particular, a history of an elevated alanine aminotransferase (ALT) or a reactive test for antibodies to Hepatitis A Virus (anti-HAV) or Antibodies to Hepatitis B surface antigen (anti-HBs) need not be a cause to defer a donor.
If a clinical history or diagnosis of viral hepatitis occurring at age 11 years or later is established, the donor will should be permanently deferred, and blood and blood components collected from the donor should not be used in the manufacture of products intended for transfusion. If viral hepatitis infection before the age of 11 is suspected to have occurred, the donor should be temporarily deferred and blood and blood components collected from the donor should not be used in the manufacture of products intended for transfusion until the circumstances are investigated and a medical opinion rendered on the significance of the history, and the conclusion drawn that there is no history or diagnosis of viral hepatitis after age 11.
Please be aware, however, that a blood center may voluntarily elect to adopt more stringent donor deferral criteria in its Standard Operating Procedures (SOPs) than those required or recommended by the FDA. Under these circumstances, FDA does require that the blood center follow its own SOPs.
There are two relevant documents available that can further clarify FDA’s current donor deferral criteria:
Memorandum to blood establishments: "Exemptions to Permit Persons with a History of Viral Hepatitis Before the Age of Eleven Years to Serve as Donors of Whole Blood and Plasma: Alternative Procedures, 21 CFR 640.120" - April 23, 1992.
Memorandum to blood establishments: "Donor Suitability Related to Laboratory Testing for Viral Hepatitis" - December 22, 1993.
I was recently deferred for an inconclusive Hepatitis B core test. Can you explain the reasoning behind the deferral?
Anti-HBc is an antibody that generally appears at the onset of clinical hepatitis and may persist for years or life. In 1987, U.S. blood banks voluntarily began anti-HBc screening of blood and blood components for transfusion. This test was intended as a surrogate non-specific test for hepatitis C (formerly called non-A, non-B hepatitis). In addition, studies of transfusion-associated hepatitis B prior to anti-HBc testing indicated that hepatitis B still occurred, despite the use of a sensitive test for hepatitis B surface antigen (HBsAg).
On September 10, 1991, FDA issued a memorandum to all registered blood establishments providing recommendations and guidance on testing for anti-HBc, donor deferral, product labeling and quarantine. FDA recommends that blood and blood components found to be repeatedly reactive for anti-HBc should not be used for transfusion. Studies have demonstrated that transfusions of blood that is reactive for anti-HBc, but negative for Hepatitis B Surface Antigen, were associated with some cases of post-transfusion hepatitis. The numbers of transfusion recipients developing hepatitis in such circumstances are indeed extremely low, but FDA is committed to ensuring the safest blood supply possible.
In addition, FDA recommends that donors having a repeatedly reactive test for anti-HBc on more than one occasion be indefinitely deferred until a licensed confirmatory test is available for use. At present, there is no licensed confirmatory test available. However, the FDA does not prevent blood banks from developing procedures more stringent than FDA's regulations and recommendations. When a blood bank incorporates a standard operating procedure, the FDA requires the blood center to specifically follow the procedures that the center has developed. Therefore, the blood bank where you donated may be following a standard operating procedure that is more rigid than current FDA recommendations.
If you have had only one reactive test for anti-HBc, then you may be eligible to donate blood again, provided that all other donor suitability criteria are met and the blood center's procedures are followed. Again, the blood bank where you donated may be following a standard operating procedure that is more rigid than current FDA recommendations and, for that reason, you may be excluded from donating.
FDA recommendations were reviewed in January 1995 when the National Institutes of Health held a Consensus Development Conference for Infectious Disease Testing for Blood Transfusions. The panel of experts, who are not government employees, based their report on presentations by investigators working in areas relevant to the consensus questions, questions and statements from the conference attendees, and closed deliberations by the panel. The panel's recommendations included continuing testing for anti-HBc as part of the donor screening process, both to prevent hepatitis B and as a surrogate marker for HIV risk. The panel also emphasized the need to improve the specificity of screening tests for anti-HBc. FDA certainly will continue to cooperate in this effort, even potentially allowing a re-entry scheme in the future. In January 1998, the issue of continuing testing for anti-HBc was discussed at FDA’s Blood Products Advisory Committee meeting. This panel of outside experts, which provides scientific advice to FDA, recommended to continue testing blood for transfusion for antibodies to hepatitis B core antigen.
Individuals can be perfectly healthy, give a negative history, and yet be carriers of one or more hepatitis viruses. Unfortunately, the presence of hepatitis viruses cannot always be detected with absolute certainty by any presently available means, including history, physical exam, or laboratory tests. While some FDA requirements and recommendations may seem inconvenient or not reasonable in all situations, they actually represent measures taken to ensure that blood and blood products are as safe as possible. There is no doubt that some persons, without hepatitis or other infectious diseases, are deferred as a result of established criteria.
If you would like further information about the NIH Consensus Conference, a summary statement can be obtained from the NIH Consensus Program Information Service, P.O. Box 2577, Kensington, MD 20891, phone 1-800-644-6627.
In addition, a copy of the September 10, 1991, memorandum entitled "FDA Recommendations Concerning Testing for Antibody to Hepatitis B Core Antigen (Anti-HBc)" can be obtained by from CBER’s web site at:
http://www.fda.gov/cber/bldmem/091091.pdf
or by contacting CBER’s Office of Communication, Training and Manufacturers Assistance at 301-827-1800.
As a gay male, why am I deferred as a potential blood donor simply because of my sexual orientation? Furthermore, I am in a monogamous relationship. I am being discriminated against. Will this recommendation be removed any time soon?
In 1983, FDA recommended donor-screening procedures to exclude individuals at increased risk for transmitting Human Immunodeficiency Virus (HIV), the virus that causes Acquired Immunodeficiency Syndrome (AIDS). These recommendations have been updated periodically since then. The exclusion of potential donors based on certain sexual histories has been discussed often, and in-depth, by FDA's Blood Products Advisory Committee (BPAC). This panel of non-FDA independent experts continues to recommend the deferral of men who have sex with other men and their recent partners. This issue was discussed at the December 11-12, 1997, BPAC meeting. The committee voted to reconsider the current recommendations for deferral of men who have had sex with other men. However, at that time the committee did not specify what the specific recommendations should be. Data on the incidence and prevalence of HIV and other viruses in men who have had sex with other men and data on HIV positive blood donors were presented at the November 23, 1998, FDA Workshop on Blood Donor Suitability. A transcript from this workshop can be obtained from CBER’s web site at:
www.fda.gov/cber/minutes/bld112398trans.pdf
The BPAC met on September 14-15, 2000 to revisit this issue. After much discussion, the BPAC recommended that men who had sex with other men since 1977 continue to be deferred from donating blood. A copy of the meeting transcript is available at:
http://www.fda.gov/ohrms/dockets/ac/cber00.htm#Blood Prducts
A test for the antibodies to HIV (previously termed HTLV-III) was licensed by FDA in 1985 and has been used to screen blood donors since that time. Studies have shown that up to 2 months may elapse between the time of infection and the time the HIV antibody test is reactive. This period of time is often referred to as the "window period." Accepting men who have had sex with other men since 1977 as blood donors increases the likelihood for the collection of HIV-positive window period blood, because epidemiologic studies have documented higher incidence and prevalence rates in these populations. On March 14, 1996, FDA recommended donor screening with a licensed test for HIV-1 antigen, which has succeeded in further reducing the window period. In addition, almost all blood collections in the U.S. are tested for HIV RNA using investigational/experimental tests under the IND regulation. This probably decreases window period risks.
FDA continues to recommend that blood donors be informed of behaviors that potentially place them at increased risk for transmitting HIV. In addition, donors are informed that there is a time interval early in infection during which any test for HIV may be negative and an infection may still be transmitted. Providing donors with this information allows them to consider their behaviors and self-exclude from donation if they participated in any of the identified risk behaviors. Note that donors do not have to specify the basis for their decision to self-defer.
In an April 23, 1992, memorandum to all blood establishments entitled, "Revised Recommendations for the Prevention of Human Immunodeficiency (HIV) Transmission by Blood and Blood Products," FDA outlined updated policies for deferral of donors based on HIV-associated signs and symptoms, medical history, laboratory test results, and certain activities that place the donor at increased risk for HIV infection. Taken together, these control measures had been effective in reducing the risk of transfusion transmission of HIV to about 1 unit per million donations. However, since 2002, the routine use of nucleic acid testing (NAT) for HIV has even further reduced the risk of transfusion transmission of HIV to about 1 unit per 2 million donations. A copy of this memorandum can be obtained from CBER’s web site at:
http://www.fda.gov/cber/bldmem/hiv042392.pdf
or by contacting CBER’s Office of Communication, Training and Manufacturers Assistance at 301-827-1800.
In the above-mentioned memorandum, certain categories of high-risk behaviors are specifically mentioned, without further elaboration, as a basis for deferral: "men who have had sex with another man even one time since 1977," "men and women who have engaged in sex for money or for drugs since 1977," and "persons who have had sex with any person meeting (these) descriptions during the preceding 12 months," are all examples of such categories. Because there is a potential danger to blood safety in making the criteria for exclusion too specific, activities encompassed by each general area of exclusion have not been described. The April 23, 1992, memorandum also addresses a variety of high risk behaviors and medical conditions that are unrelated to sexual preference, including past or present drug use, hemophilia or other blood clotting disorders, being treated for syphilis or gonorrhea or receiving a transfusion, as well as asking whether a person has had a positive test for antibodies to HIV.
Although a potential individual donor may practice safe sex, persons who have participated in high-risk behaviors are, as a group, still considered to be at increased risk of transmitting HIV. Safe sex practices reduce, but do not eliminate, the risk of the transmission of AIDS. Several Centers for Disease Control and Prevention (CDC) studies have shown that many people who believe they are engaging in safe sex practices are not doing so, either because of poor technique (i.e., condom is incorrectly used) or lack of consistency (i.e., proper safe sex practices are not used at every sexual encounter). The August 6, 1993, Morbidity and Mortality Weekly Report (MMWR) will provide you with further information on this subject.
FDA believes that there is scientific justification for screening out all potential donors who are men who have had sex, even once, with another man since 1977, and for screening out the recent (within 12 months) sexual partners of such men. Since 1983, CDC and, the previously mentioned, BPAC have been advising FDA on high-risk categories as a basis for deferral of potential blood donors. Studies have shown that men with a history of male to male sex since 1977 may be infected with HIV and/or may have evidence of a lifestyle that potentially exposes them to HIV. In a recent "HIV/AIDS Surveillance Report" CDC's states that men who have sex with men account for the largest proportion (38%) of new AIDS cases reported in the United States from 1996-1997. Intravenous drug users (23%) are the second highest proportions of reported cases. Studies also show that men with a history of male to male sex since 1977 are also at increased risk of transmitting hepatitis viruses. For further information on CDC studies you may wish to contact:
Center for Disease Control and Prevention
Mailstop D-21
1600 Clifton Road
Atlanta, GA 30333
http://www.cdc.gov/
FDA donor exclusion criteria are intended to utilize all prudent measures, which may reduce the potential risk for transmitting HIV and other infectious diseases. FDA’s conservative approach, originates from several published sources and public discussions. This approach, consistent with external advice, has the potential to decrease transmission of HIV virus from entering the blood supply. FDA is very much aware that strict exclusion policies eliminate some safe donors in the attempt to maximally protect the nation's blood supply by deferring the largest number of donors at increased risk for HIV infection. FDA continues to review and discuss donor deferral recommendations within the public health service (FDA, CDC, and National Institutes of Health) and at open public BPAC meetings, scientific meetings, etc.
Recently, I was informed by my local blood bank that I would no longer be able to donate blood because of an indeterminate test result for HIV. My physician has tested my blood and determined that I am negative for any infectious diseases. In light of the fact that there is a reported blood shortage, how can I be deferred if it has been determined that I do not have HIV?
The Food and Drug Administration (FDA) is responsible for establishing policies which will maximally protect the recipients of blood products. Part of the protective strategy includes screening of all blood and plasma collections for markers of transmissible infectious diseases. Unfortunately, current technology does not permit perfect testing, i.e., 100% sensitivity with the absence of false positive tests.
The possibility does exist for indeterminate or inconclusive test results to occur when HIV-1 testing is performed. FDA recognizes that the deferral of donors who have had a repeatedly reactive screening test result may exclude individuals who probably have little risk of HIV-1 or other viral infection. FDA's intent is to eliminate blood that has the potential to transmit HIV-1 viral infections from the nation’s blood supply. Although the need for donors is great, it is in the best interests of the recipients of such donations to err on the side of safety. Unfortunately, once an indeterminate or inconclusive result is obtained, the donor should be indefinitely deferred.
FDA established a mechanism for previously deferred donors to re-enter the donor program. Under certain circumstances a donor with an indeterminate Western Blot may be tested for possible re-entry after a six-month period if an unlicensed Western Blot was used for the original test. A licensed Western Blot must be used for re-entry. If a licensed Western Blot was used for the original test, a donor with indeterminate results may not currently be considered for re-entry.
Although it is highly unlikely that individuals with indeterminate or inconclusive test results are actually infected with HIV, FDA is erring on the side of safety to assure that the nation’s blood products are as safe as possible. Although this policy may disqualify some healthy individuals from donating blood, it has proven effective in protecting the nation’s blood supply.
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