Requalification Method for Reentry of Blood Donors Deferred Because of Reactive Test Results for Antibody to Hepatitis B Core Antigen (Anti-HBc)

Name of Guidance
Requalification Method for Reentry of Blood Donors Deferred Because of Reactive Test Results for Antibody to Hepatitis B Core Antigen (Anti-HBc)

Status of Guidance
Final

When was the Guidance released?
May 2010

Which organization released the Guidance?
Center for Biologics Evaluation and Research (CBER)

Target Audience
Organizations (such as hospitals and blood banks) that collect either whole blood or blood components to be used for medical use such as transfusions.

Laws and Regulations Referenced
21 CFR 610.40(a): Any organization that collects human blood or blood components for medical use (such as transfusions) must first test a sample of each potential donor’s blood for Human Immunodeficiency Virus (HIV) types 1 and 2, Hepatitis B virus, Hepatitis C virus, and Human T-lymphotropic virus types I and II.

21 CFR 610.40(h)(1) and (2): Human blood or blood components that have tested positive for 1 or more of the diseases listed in 21 CFR 610.40(a) may not be shipped or used EXCEPT if the blood is for use by the original donor, or if the shipper gets written permission from FDA and labels the package with the appropriate warnings required by FDA. Also, donated blood that tests positive for anti-HBc (but none of the other diseases listed in 21 CFR 610.40(a)) may be used to extract proteins from the plasma portion of whole blood without FDA approval.

21 CFR 610.41(a) and (b): Organizations that collect human blood or blood components must refuse any blood donations (now and in the future) from donors whose blood tests positive for the diseases listed in 21 CFR 610.40(a) and syphilis EXCEPT if the donor is requalified by an FDA-approved method or if the donor tests positive for anti-HBc or anti-HTLV (types I and II) on only one occasion but never again upon retesting.

Definitions

• Anti-HBc: An antibody for Hepatitis B virus commonly used to screen would-be blood donors for Hepatitis B.
• Antibody: A protein produced by the body’s immune system in response to the presence of a harmful substance (known as an antigen) such as a virus or bacterium.
• Antigen: A foreign substance such as a virus or bacterium that is identified by the body’s immune system as harmful.
• Blood bank: An organization that collects, tests, and stores human blood for medical use.
• Blood transfusion: A procedure in which blood is given intravenously.
• Deoxyribonucleic acid (DNA): Genetic material found in human cells, bacteria, viruses, and other living organisms.
• False positive: A lab test result that indicates the tested person has a certain disease when in fact they do not.
• Hepatitis B: A liver disease that can cause cirrhosis, liver failure, or liver cancer.
• Hepatitis B Antigen (HBsAg): An antigen that indicates the presence of Hepatitis B virus. A positive test for HBsAg indicates active Hepatitis B infection.
• Hepatitis B virus nucleic acid test (HBV NAT): A blood test that detects the presence of nucleic acids specific to Hepatitis B virus. A positive test indicates active Hepatitis B infection.
• Hepatitis B virus (HBV): The virus that causes Hepatitis B.
• Negative test result: A lab test result that indicates the tested person does not have the disease for which they were screened.
• Nucleic acid: A small piece of genetic material. DNA contains 4 nucleic acids: adenosine, cytosine, guanine, and thymine.
• Plasma: A components of whole blood. The clear, yellow liquid in which red blood cells, white blood cells, and platelets are suspended.
• Positive test result: A lab test result that indicates the tested person has the disease for which they were screened.
• Whole blood: Blood that contains all the components of blood: red blood cells, white blood cells, platelets, and plasma.

Background
Hepatitis B is a liver disease that can be transmitted from person to person in blood and other bodily fluids. To prevent transmission during blood transfusions, blood banks, hospitals, and other organizations that collect whole blood and/or components of blood pre-screen donors to determine if they have Hepatitis B. Anyone who tests positive is not permitted to donate blood.

However, the most commonly available screening test (which detects the presence of an antibody of Hepatitis B, known as anti-HBc, in a sample of the potential donor’s blood) is not 100% accurate and occasionally donors will test positive for Hepatitis B during screening when in fact they do not have the disease. These “false positives” prevent blood banks and hospitals from receiving badly-needed blood donations. Researchers who conducted a study funded by the National Heart, Blood and Lung Institute estimated that at least 200,000 potential donors who have received multiple false positive anti-HBc tests but otherwise met all criteria for being blood donors could be eligible to give blood again.



Summary
In spite of precautions, the transmission of disease-causing viruses like Human Immunodeficiency Virus (HIV) and Hepatitis B and C viruses from transfusions of donated blood can occur. Transmission is relatively rare but researchers estimate that approximately 1 in 205,000 to 1 in 269,000 units of donated blood carries Hepatitis B Virus (HBV). As a result, blood banks and other organizations that collect blood screen would-be donors for the presence of an antibody to HBV known as anti-HBc. Would-be donors who test positive are deferred but may donate in the future if they receive a negative test result on their second anti-HBc test. Would-be donors who test positive for anti-HBc more than once are blocked from donating blood indefinitely.

However, the anti-HBc test is not fool-proof and a substantial number of blood donors (approximately 20,000 per year) are turned away due to a positive test result when they do not have Hepatitis B.

In 2004, FDA and the Blood Products Advisory Committee (BPAC) held a meeting to discuss how would-be donors who had tested positive for anti-HBc more than once could be eligible again to donate blood. This Guidance is an outcome of that meeting and the identification of a highly sensitive test that can confirm whether an anti-HBc positive would-be donor actually has Hepatitis B. The new test, called Hepatitis B Virus Nucleic Acid Test (HBV NAT), detects pieces of DNA from the Hepatitis B virus. These pieces of DNA are present in blood only when the person is infected with the virus. A third test, which looks for the Hepatitis B antigen (HBsAg) which is present during active Hepatitis B infection, was added to the protocol to help protect the nation’s blood supply.

The resulting recommendation allows anti-HBc positive donors to give blood if they receive negative tests for HBsAg, anti-HBc, and HBV DNA by NAT at least 8 weeks (56 days) after the last positive anti-HBc test.



Rationale
Existing laws (21 CFR 601.40 and 21 CFR 61.41) require organizations that collect blood and blood components for medical use to test donor blood for Hepatitis B and refuse to collect or use blood from would-be donors who have tested positive for anti-HBc (an antibody of Hepatitis B virus) unless there is an FDA-approved method for requalifying donors. Before this Guidance was published, there was no such method and blood banks and hospitals had no choice but to reject donations from people with more than 1 positive anti-HBc test regardless of whether they actually had Hepatitis B. This Guidance describes the first such FDA-approved method and will help to expand the blood donor pool.


Resulting Recommendations
Would-be donors who have previously tested positive for anti-HBc on more than one occasion may regain eligibility for donating blood if:

1. At least 8 weeks (56 days) after the last positive anti-HBc test they are retested using FDA-licensed tests for HBsAg, anti-HBc, and HBV DNA by NAT. 

   AND
2. They receive negative test results on all 3 tests

   AND
3. They meet all other eligibility criteria for blood donors

Would-be donors have previously tested positive for anti-HBc on more than one occasion and who receive a positive result for any of the 3 FDA-licensed tests (HBsAg, anti-HBc, and HBV DNA by NAT) upon retesting after 8 weeks are barred from giving blood indefinitely.


Impact
Donated blood is a critical source of blood and blood products used to save the lives of millions of Americans who need transfusions due to sickle cell disease, cancer, traumatic accidents, surgery, and other medical conditions. Organizations such as the American Red Cross frequently report shortages in the supply to donated blood. This problem is compounded by the enormous baby boomer population which will require increasing amounts of donated blood as they age even as they become ineligible to donate blood and replenish the supply. Allowing would-be donors who have been rejected due to multiple positive anti-HBc tests to donate blood if they meet the criteria described in the Guidance expands the pool of donors and the amount of donated blood available while still keeping the blood supply safe.