Hepatitis B Virus (HBV) and Our Industry: FDA’s Upcoming Guidance
Welcome to our next discussion on the Food and Drug Administration’s (FDA) updates for Hepatitis B Virus (HBV), “Recommendations to Reduce the Risk of Transmission of Hepatitis B Virus (HBV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)”. This guidance is still currently in its comment period and once implemented, will supersede the guidance, “Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), Guidance for Industry,” dated August 2007 and the guidance “Use of Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products” dated August 2016.
Hepatitis is an inflammation of the liver and a major global health problem. There are 5 main hepatitis viruses, referred to as types A, B, C, D and E. These 5 types are of greatest concern because of the burden of illness and death they cause and the potential for outbreaks and epidemic spread. In particular, types B and C lead to chronic disease in hundreds of millions of people and, together, are the most common cause of liver cirrhosis and cancer 1 . The FDA identified HBV as a relevant communicable disease agent or disease (RCDAD) and requires donor screening and testing for specific risk factors and conditions associated with this infection as it is transmissible by HCT/Ps, organs, body fluids, and transfusion of blood products.
FDA revised recommendations for:
1. Donor screening that includes reducing certain time-based risk factors and conditions, and
2. Assessing every HCT/P donor for HBV risk using the same individual risk-based questions regardless of sex or gender.
FDA requires establishments to review relevant medical records and ask questions about the donor’s medical history and relevant conditions and behavioral risks including risk factors for RCDADs.
Risk factors for HBV include:
1. Persons who have ever had a positive or reactive screening test for HBV
2. Persons who have engaged in non-prescription injection drug use in the preceding 3 months, including intravenous, intramuscular, or subcutaneous injections
3. Persons who have had sex (unless specified as “anal sex,” the term “sex” or “sexual contact” refers to vaginal, anal, or oral sex, regardless of whether a condom or other protection is used) in exchange for money or drugs or other payment in the preceding 3 months
4. Persons who have had sexual contact in the preceding 3 months with any individual who has ever had a positive test for HBV infection
5. Persons who have had sexual contact in the preceding 3 months with any individual who has exchanged sex for money, drugs or other payment. If there is any uncertainty about when their sexual partner exchanged sex for money, drugs or other payment, the person is ineligible for 3 months
6. Persons who have had sexual contact in the preceding 3 months with any individual who has engaged in non-prescription injection drug use. If there is any uncertainty about when their sexual partner engaged in non-prescription injection drug use, the person is ineligible for 3 months
7. Persons who have had a new sexual partner (the following examples would be considered having sex with a new partner: having sex with someone for the first time; or having had sex with someone in a relationship that ended in the past and having sex again with that person) in the preceding 3 months and have had anal sex in the preceding three months
8. Persons who have had more than one sexual partner in the preceding 3 months and have had anal sex in the preceding three months
9. Persons who have been exposed in the preceding 3 months to known or suspected HBV-infected blood through percutaneous inoculation (e.g., needle stick) or through contact with an open wound, non-intact skin, or mucous membrane
10. Persons who have been in lock up, jail, prison, or a juvenile correctional facility for more than 72 consecutive hours in the preceding 3 months
11. Persons who have lived with (resided in the same dwelling) another person who has HBV infection in the preceding 3 months
12. Persons who have undergone tattooing, ear piercing or body piercing in the preceding 3 months, in which sterile procedures were not used, e.g., contaminated instruments and/or ink were used, or shared instruments that had not been sterilized between uses were used.
A person may be eligible, for example, if a tattoo was applied by a state regulated entity with sterile needles and non-reused ink, or if ear or body piercing was done using single-use equipment
13. Children 1 month of age or younger who were born to a mother with, or at risk for, an HBV infection; see risk factors above
Clinical evidence of HBV infection for ineligible donors with relevant medical record review may include:
1. A prior positive or reactive screening test for HBV;
2. Unexplained jaundice;
3. Unexplained hepatomegaly;
4. Generalized lymphadenopathy; and/or
5. Unexplained generalized rash or fever.
Laboratory data records that may assist in determining eligibility where there is an inconclusive history of hepatitis infection (note: these test results should not be used alone to determine donor eligibility):
1. alanine aminotransferase (ALT);
2. aspartate aminotransferase (AST);
3. bilirubin; or
4. prothrombin time.
Indications of high-risk behavior associated with HBV that would increase the donor’s RCDAD risk or physical evidence of HBV are:
1. Physical evidence for risk of sexually transmitted diseases and infections, such as perianal lesions, genital ulcerative disease, herpes simplex, or chancroid (when making a donor eligibility determination, establishments should consider these findings in light of other information obtained about the donor)
2. Physical evidence of nonmedical percutaneous drug use such as needle tracks; the examination should include examination of tattoos, which might be covering needle tracks
3. Physical evidence of recent tattooing, ear piercing, or body piercing. Persons who have undergone tattooing, ear piercing, or body piercing in the preceding 3 months, in which sterile procedures were not used (e.g., contaminated instruments and or/ink were used), or instruments that had not been sterilized between uses were used. A person may be eligible, for example, if a tattoo was applied by a state regulated entity with sterile needles and non-reused ink, or if ear or body piercing was done using single-use equipment
4. Unexplained jaundice, hepatomegaly, or icterus. (Note: Hepatomegaly may not be apparent in a physical assessment unless an autopsy is performed)
5. Generalized lymphadenopathy
6. Unexplained generalized rash or fever
Current Donor Screening Tests approved by the FDA:
1. FDA-licensed donor screening test for hepatitis B surface antigen (HBsAg); and
2. FDA-licensed donor screening test for total antibody to hepatitis B core antigen (total anti-HBc means IgG and IgM); and
3. FDA-licensed donor screening Nucleic Acid Test for HBV (HBV NAT); or a combination or multiplex NAT that includes HBV.
Any HCT/P donor whose specimen tests negative (or non-reactive) for all three assays (i.e., HBsAg, total anti-HBc (IgG and IgM), and HBV NAT) is considered to be negative (or non-reactive) when making a donor eligibility determination. Note that a negative (or non-reactive) test does not necessarily mean that a donor is eligible; donor screening also applies as described above.
Any HCT/P donor whose specimen tests positive (or reactive) using any of the assays (i.e., HBsAg, total anti-HBc (IgG and IgM), or HBV NAT) is considered ineligible (21 CFR 1271.80(d)(1)).
Reference the FDA licensed donor screening tests here:
The impact to the tissue industry: the American Association of Tissue Banks (AATB) provided feedback to the FDA February 6, 2025, in support of the blood banking community who is also requesting that FDA considers the discontinuance of HBsAg testing as tissue establishments already perform anti-HBc and HBV nucleic acid testing on donors. Read more about it here:
https://www.aatb.org/government-advocacy-correspondences
Reference the FDA guidance here:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-reduce-risk-transmission-hepatitis-b-virus-hbv-human-cells-tissues-and-cellular-and
Check back as we continue following and posting updates!
References:
1 https://www.who.int/news-room/questions-and-answers/item/hepatitis