Blood Supply:

FDA Oversight and Remaining Issues of Safety

PEMD-97-1: Published: Feb 25, 1997. Publicly Released: Mar 12, 1997.

Additional Materials:

Contact:

Marcia G. Crosse
(202) 512-7250
contact@gao.gov

 

Office of Public Affairs
(202) 512-4800
youngc1@gao.gov

Pursuant to a congressional request, GAO evaluated the Food and Drug Administration's (FDA) "layers of safety" that provide the framework for regulating and monitoring the U.S. blood industry, focusing on the actual and potential vulnerabilities in the layers of safety that may present a threat to the public health.

GAO found that: (1) the transmission of human immunodeficiency virus (HIV) by transfusion decreased dramatically after HIV testing for donors was introduced in 1985, and more and better tests for other diseases also have reduced the risks from blood transfusions; (2) while the blood supply is very safe, no amount of federal regulation can entirely eliminate blood-transfusion risks because of human error, technological limitations of state-of-the-art tests, and the biological nature of the product itself; (3) within the overlapping layers of safety, GAO found areas where FDA can take action that would further improve the safety of the blood supply: (a) the lack of a uniform donor questionnaire allows variability in donor screening; (b) the lack of mandatory deferral notification allows some donors who have tested positive for viruses to unwittingly attempt donation again; (c) untested units donated for self-use may inadvertently be used for unintended recipients; and (d) FDA has been slow to investigate error and accident reports that may warrant a recall; (4) FDA does not require unlicensed facilities, those that do not engage in the sale, barter, or exchange of blood products across state lines, to report errors and accidents; (5) because unlicensed facilities constitute more than two thirds of all blood facilities that, together, produce 10 percent of the nation's blood, FDA has not fully monitored the quality of this portion of blood products; (6) FDA's inspections for both licensed and unlicensed blood facilities appear to be inconsistent in focus, scope, and documentation; (7) in addition, these inspections are often not conducted within time periods set by FDA's own guidelines; (8) FDA does not maintain a central repository for inspection reports and, thus, does not examine national trends; and (9) GAO's survey results also indicated confusion within the blood industry regarding the interpretation for FDA policy guidance and regulations.

Recommendations for Executive Action

  1. Status: Closed - Implemented

    Comments: FDA issued a document to clarify its position on the use of guidance documents ("The Food and Drug Administration's Development, Issuance, and Use of Guidance Documents"). In this document, FDA outlines the definition of guidance, the legal effect of such documents, procedures for developing guidance, and FDA employee training on how to develop and use guidance documents. This document should mitigate industry's complaints regarding how such documents are used and past practices by FDA of using guidance documents to set policy.

    Recommendation: The Secretary of Health and Human Services should publish in the form of regulations the guidelines that the Secretary believes are essential to ensure the safety of the nation's blood supply and that it clarify its position on the extent to which facilities should adopt the agency's guidelines and memoranda in order to remain in compliance with HHS regulations. The blood industry has consistently identified this ambiguity as a source of confusion and frustration and has raised concerns about the practice of setting standards through inspection observations and warning letters. Policy in the form of guidelines does not have the enforcement power or public input of formal regulations, whereas the use of regulations may increase compliance and decrease the likelihood that guidelines will be misinterpreted or applied inconsistently.

    Agency Affected: Department of Health and Human Services

  2. Status: Closed - Implemented

    Comments: FDA proposed new regulations requiring unlicensed blood facilities to report errors and accidents to FDA. This was being done to provide FDA with a more accurate surveillance of the nation's blood supply and to facilitate a rapid response where the public health might be at risk. This proposed regulation was published in the Federal Register on September 23, 1997 ("Biological Products: Reporting of Errors and Accidents in Manufacturing").

    Recommendation: The Secretary of Health and Human Services should require unlicensed blood facilities to report all error and accident reports to the agency. GAO's information, analysis, and conclusions highlight the need for such a requirement. Such information will provide FDA with additional data from which to direct inspections of particular blood facilities as well as the blood industry as a whole.

    Agency Affected: Department of Health and Human Services

  3. Status: Closed - Implemented

    Comments: On March 20, 1998, FDA issued guidance for the direct notification of persons who received blood or blood components from donors who subsequently tested positive for HCV. In addition, blood establishments were to identify repeat donors who test positive for HCV and their previously distributed units dating back 10 years or to the date 12 months prior to the donor's most recent negative screening test (prospective notification). FDA also issued a final rule relating to HIV that requires notification of consignees and transfusion recipients. This final rule was published in the Federal Register on September 9, 1996. It required quarantine of all donations from 5 years from the date of the positive test result and notification of consignees and transfusion recipients.

    Recommendation: The Secretary of Health and Human Services should require lookback in such situations to find implicated blood units that have not been transfused or further manufactured into blood components or plasma derivatives. The reasonable time period for lookback varies with each virus, and decisions should be made in consultation with the blood industry. Thus, it might be determined that lookback procedures should be implemented beginning at a specific date when a memorandum to blood facilities is made final.

    Agency Affected: Department of Health and Human Services

  4. Status: Closed - Implemented

    Comments: On March 20, 1998, FDA issued guidance for the direct notification of persons who received blood or blood components from donors who subsequently tested positive for HCV ("Guidance for Industry: Supplemental Testing and Notification of Consignees of Donor Test Results for Antibody to Hepatitis C virus (Anti-HCV"). FDA also issued a final rule relating to HIV that requires notification of consignees and transfusion recipients. This final rule was published in the Federal Register on September 9, 1996, ("Current Good Manufacturing Practices for Blood and Blood Components: Notification of Consignees Receiving Blood and Blood Components at Increased Risk for Transmitting HIV Infection").

    Recommendation: The Secretary of Health and Human Services should require that transfusion recipients be notified when they have been transfused with blood from a donor whose subsequent donations were found positive in confirmatory testing. Notifying recipients of blood that is negative or indeterminate on a confirmatory test should be left to the discretion of their physicians. This recommendation is intended to reduce the potentially adverse public health consequences of not informing recipients.

    Agency Affected: Department of Health and Human Services

  5. Status: Closed - Implemented

    Comments: FDA issued a final rule relating to HIV that requires confirmatory testing and notification of consignees and transfusion recipients. This final rule was published in the Federal Register on September 9, 1996 ("Current Good Manufacturing Practices for Blood and Blood Components: Notification of Consignees Receiving Blood and Blood Components at Increased Risk for Transmitting HIV Infection"). On March 20, 1998, FDA issued guidance for confirmatory testing to be performed on all donations that test repeatedly reactive for HCV ("Guidance for Industry: Supplemental Testing and Notification of Consignees of Donor Test Results for Antibody to Hepatitis C virus (Anti-HCV")). The only FDA-licensed confirmatory tests that are available are for HIV, HCV, and HBV (hepatitis B).

    Recommendation: The Secretary of Health and Human Services should require confirmatory testing of all repeatedly reactive viral test results for which there is a licensed confirmatory test. GAO recommends this requirement in order that the blood facility be given as much information as possible when it considers whether to conduct lookback and how to counsel donors and recipients who have a positive confirmatory test. However, the information that should be provided if confirmatory tests are negative or indeterminate should be left to the discretion of the blood facilities and the recipients' physicians.

    Agency Affected: Department of Health and Human Services

  6. Status: Closed - Implemented

    Comments: On August 19, 1999, FDA published a proposed rule to revise the general biological product standards. This rule would (1) require screening tests for evidence of infection due to communicable disease agents for autologous donations in order to reduce the risk of transmission of communicable disease by untested units inadvertently entering the blood supply; (2) require supplemental (additional, more specific) testing of all donations that are repeatedly reactive by screening tests for which there are supplemental (additional, more specific) tests; and (3) codify as requirements those recommendations that FDA has issued that are necessary to ensure blood safety, including testing for evidence of infection due to HIV, HBV, HCV, and HTLV. Consistent with one of GAO's recommendations, FDA has been requiring testing of autologous blood donations for evidence of HIV infection since 2001.

    Recommendation: The Secretary of Health and Human Services should require viral testing for all autologous units. Since the practice of viral testing for autologous units varies and since mislabeling and transfusion errors do occur with some frequency, HHS should require that the blood industry minimize this vulnerability in the system by testing all units, whether autologous or allogeneic.

    Agency Affected: Department of Health and Human Services

  7. Status: Closed - Not Implemented

    Comments: FDA is awaiting the results of both a Centers for Disease Control study to determine the rates of bacteria-associated transfusion reactions from different blood components, and an NHLBI-sponsored study of inactivation techniques that could kill bacteria in platelets. FDA will then reevaluate the issue of requiring that blood facilities' quality assurance programs include processes that monitor for bacterial contamination. Since 2001, FDA has cleared three devices for quality control of bacterial contamination in platelet products. However, standards for control of bacterial contamination in platelets are still evolving due to underlying scientific uncertainties.

    Recommendation: The Secretary of Health and Human Services should require blood facilities' quality-assurance programs to include processes that monitor for bacterial contamination. Bacteria can enter blood products during collection through a donor's skin contamination or illness. Bacteria can also be introduced during manufacturing, as in the water baths in the making of certain blood components. Both collection and manufacturing processes are within the control of blood facilities and could be modified if quality-control information suggested that products were bacterially contaminated.

    Agency Affected: Department of Health and Human Services

  8. Status: Closed - Implemented

    Comments: On June 11, 2001, FDA published a final rule to require blood and plasma establishments to notify donors, including autologous donors, of their deferral due to test results for communicable disease agents or failure to satisfy suitability criteria with the intent of reducing the risk of transmission of communicable disease through the use of blood, blood components, and blood derivatives. Under the final rule, blood and plasma establishments would notify the donors that they have been deferred and the reason for the deferral and notify the referring physician for an autologous donor; provide information concerning appropriate medical followup and counseling; describe the types of donations the donors should not make in the future; and discuss the possibility that the donor may be found suitable in the future, where appropriate.

    Recommendation: The Secretary of Health and Human Services should require that blood facilities notify donors who have been permanently deferred. This notification should be based on positive confirmatory results for viral markers (for the viruses that have licensed confirmatory tests) and all other medical reasons that result in permanent deferral (for example, the intake of human pituitary growth hormone). Notification should include the reasons for the permanent deferral, possibilities for re-entry as a donor, and counseling or referral to the donor's physician (including, when pertinent, actions to be taken to minimize transmission of viruses to others). Such notification is recommended because of the public health consequences of not informing donors.

    Agency Affected: Department of Health and Human Services

  9. Status: Closed - Implemented

    Comments: On April 24, 1997, FDA formalized a new inspection program that addressed the concerns noted in the recommendation, including the use of a more specialized cadre of inspectors and placing the inspection program under one agency unit. The latter effort was done to reduce possible opportunities for inconsistent action and interpretation between FDA representatives.

    Recommendation: The Secretary of Health and Human Services should correct the problems GAO has identified in FDA inspection processes. FDA needs to perform statistical analyses of inspection reports, develop policies to FDA inspectors that would require them to list on the inspection reports what they had observed during an inspection, publish better guidance to inspectors and district offices on the types of activities that warrant observation reports and warning letters, and ensure that all blood facilities are inspected in a timely fashion. GAO believes that these changes are necessary to improve FDA's ability to discriminate between facilities that comply and those that do not.

    Agency Affected: Department of Health and Human Services

 

Explore the full database of GAO's Open Recommendations »

Sep 15, 2016

Sep 14, 2016

Sep 12, 2016

Sep 9, 2016

Sep 6, 2016

Aug 31, 2016

Looking for more? Browse all our products here