Pipeline News for Hepatitis B Surface Antigen Testing in Blood Banking and Will This Impact HCT/Ps?
Welcome back! For those in the biologics and blood banking industry, the Food and Drug Administration (FDA) just released their draft guidance on July 15, 2025, for hepatitis B surface antigen (HBsAg) testing, “Recommendations for Testing Blood Donations for Hepatitis B Surface Antigen”. This guidance is now in its comment period and, once implemented, will supersede the “Guidance for Industry: Use of Nucleic Acid Tests on Pooled and Individual Samples From Donors of Whole Blood and Blood Components, Including Source Plasma, to Reduce the Risk of Transmission of Hepatitis B Virus,” dated October 2012. Why is this important? Will this potentially impact the human cells, tissues, and cellular and tissue-based products (HCT/Ps) industry?
Currently, in the blood banking industry (as well as the tissue banking industry), for donor eligibility determination, the donor is required to submit a blood sample to be tested for infectious diseases that could be transmitted through infusion (or for HCT/Ps, through transplantation). These required infectious diseases include at a minimum, but are not limited to [1] :
Human Immunodeficiency Virus – HIV
Hepatitis B Virus – HBV
Hepatitis C Virus – HCV
Syphilis
Human T-lymphotropic Virus – HTLV I and II (where applicable)
West Nile Virus (where applicable)
Chagas disease (where applicable)
As part of screening to mitigate relevant transfusion-transmitted infections (RTTIs) for Whole Blood and blood components, including Source Plasma (for HCT/Ps – RCDADS, that is, relevant communicable disease agents or disease), blood establishments must perform these screening tests using FDA licensed, approved, or cleared test methods to reduce adequately and appropriately the risk of transmission of RTTIs [2] .
For HBV, areas for testing include acute, chronic, and occult versions [3] :
Acute: people may have short-term illness that occurs within the first six (6) months after exposure with mild illness, some could experience severe illness, or be asymptomatic with no symptoms
Chronic: people who have lifelong infection that could cause serious health issues such as liver damage, cirrhosis, liver cancer, and death.
Occult [4] : small fraction of people who have low level chronic viremia where HBsAg is absent in the serum but HBV DNA is detectable
Currently, FDA recommends testing each blood sample for the following markers: HBsAg, anti-HBc (except Source Plasma), and HBV DNA. This combination of tests detects acute (i.e., HBsAg, HBV DNA by NAT), chronic (i.e., HBsAg, HBV DNA by NAT, and anti-HBc), and occult (i.e., anti-HBc, HBV DNA by NAT) HBV infections. The residual risk of HBV transmission by blood transfusion has decreased since implementation of FDA’s testing recommendations for HBV DNA by NAT by U.S. blood establishments in 2012 [2] .
The guidance recommends that when donations, other than for Source Plasma, are tested for HBV DNA by nucleic acid tests (NAT) and for antibody to hepatitis B core antigen (anti-HBc) using FDA licensed, approved, or cleared screening tests in accordance with the manufacturer’s instructions, testing for HBsAg is not necessary to reduce adequately and appropriately the risk of transmission of HBV 1 (Source Plasma is the exception and still requires HBsAg and HBV NAT testing). This thought is based on data collected between the United States, Germany, and the Netherlands where the studies demonstrated that screening blood donations by HBV NAT is effective in detecting early (acute) and ongoing infection, and screening for anti-HBc is effective in detecting chronic or occult (HBsAg nonreactive) HBV infection. Anti-HBc typically persists for life and is detected even when HBV DNA may be suppressed below detectable levels or only intermittently detected by screening tests. The combination of HBV NAT in detecting acute cases and the contribution of anti-HBc testing, especially in the detection of chronic infections, is effective in detecting HBV infection throughout the entire clinical course of HBV infection. Therefore, the FDA concludes that the available information supports the safety of discontinuing HBsAg screening when donations are tested for both HBV DNA by NAT and anti-HBc.
What does this mean for the HCT/P industry? Currently, it is unlikely that this would apply, although it could be a possibility in the future if enough data proves otherwise and sufficient determination of HBV infection can be mitigated. Essentially, HBsAg testing will continue for the HCT/P industry as this is a vital part of ensuring safe and effective transplantation in preventing or minimizing the risk of HBV transmission to the public. Since this guidance is still in its comment period, more information is to come!
Keep checking back as we continue watching to see how this change, if implemented in the blood banking industry, could potentially impact the HBV testing guidelines for the HCT/P industry in the future!
References:
[1] https://www.ecfr.gov/current/title-21/chapter-I/subchapter-F/part-610
[3] https://www.cdc.gov/hepatitis-b/about/index.html
[4] https://www.cdc.gov/hepatitis/statistics/surveillanceguidance/HepatitisB.htm