HEPAGAM B Solution for infusion Ref.[10823] Active ingredients: Human hepatitis B immunoglobulin

Source: FDA, National Drug Code (US)  Revision Year: 2020 

Product description

HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), is a solvent/detergent-treated sterile solution of purified gamma globulin containing anti-HBs. It is prepared from plasma donated by healthy, screened donors with high titers of anti-HBs that is purified by an anion-exchange column chromatography manufacturing method9,10. HepaGam B is formulated as a 5% (50 milligrams per milliliter) protein solution with 10% maltose and 0.03% polysorbate 80 at pH 5.6. It is available in 1 milliliter and 5 milliliters single dose vials. The product appears as a clear to opalescent liquid. HepaGam B does not contain mercury. It contains no preservatives. This product is intended for single use. HepaGam B may be administered intravenously or intramuscularly dependent upon indication [see Dosage and Administration (2)]. The source plasma used in the manufacture of this product was tested by FDA licensed Nucleic Acid testing (NAT) for HIV-1, HBV and HCV and found to be negative. Plasma also has been tested by in-process NAT for hepatitis A virus (HAV) and parvovirus B19 (B19) via minipool testing and the limit for B19 in the manufacturing pool is set not to exceed 104 IU of B19 DNA per milliliter.

The manufacturing process contains two steps implemented specifically for virus clearance. The solvent and detergent step (using tri-n-butyl phosphate and Triton X-100) is effective in the inactivation of enveloped viruses, such as hepatitis B, hepatitis C and HIV11. Virus filtration, using a Planova 20N virus filter, is effective for the removal of viruses based on their size, including some non-enveloped viruses12. These two viral clearance steps are designed to increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. In addition to these two specific steps, the process step of anion-exchange chromatography was identified as contributing to the overall viral clearance capacity for small non-enveloped viruses.

The inactivation and reduction of known enveloped and non–enveloped model viruses were validated in laboratory studies as summarized in Table 4. The viruses employed for spiking studies were selected to represent those viruses that are potential contaminants in the product, and to represent a wide range of physiochemical properties in order to challenge the manufacturing process’s ability for viral clearance in general.

Table 4. Virus Reduction Values Obtained Through Validation Studies8:

 Enveloped Non-Enveloped
Genome RNA DNA RNA DNA
Virus HIV-1BVDVPRVHAVEMCMMV PPV
Family retro flavi herpes picorna parvo
Size (nm) 80-100 50-70 120-200 25-30 30 20-25 18-24
Anion Exchange Chromatography (partitioning) Not evaluated 2.3 n.e. 3.4 n.e.
20N Filtration (size exclusion) ≥4.7 ≥3.5 ≥5.6a n.e. 4.8 n.e. 4.1
Solvent/Detergent (inactivation) ≥4.7 ≥7.3 ≥5.5 Not evaluated
Total Reduction (log10) ≥9.4 ≥10.8 ≥11.1 2.3 4.8 3.4 4.1

Abbreviations:
HIV-1: human immunodeficiency virus-1; relevant virus for human immunodeficiency virus-1 and model for HIV-2
BVDV: bovine viral diarrhea virus; model virus for hepatitis C virus (HCV) and West Nile virus (WNV)
PRV: pseudorabies virus; model for large enveloped DNA viruses, including herpes
HAV: human hepatitis A virus; relevant virus for HAV and model for small non-enveloped viruses in general
EMC: encephalomyocarditis virus; model for HAV and for small non-enveloped viruses in generalMMV: murine minute virus; model for human parvovirus B19 and for small non-enveloped viruses in general
PPV: porcine parvovirus; model for human parvovirus B19 and for small non-enveloped viruses in general
n.e.: not evaluated
a The PRV was retained by the 0.1 µm pre-filter during the virus validation. Since manufacturing employs a 0.1 µm pre-filter before the 20N filter, the claim of ≥5.6 reduction is considered applicable.

The product potency is expressed in international units (IU) by comparison to the World Health Organization (WHO) standard Hepatitis B Immune Globulin. Each vial contains greater than 312 IU per milliliter. The measured potency of each lot is stamped on the vial label [see Dosage Forms and Strengths (3)].

Dosage Forms and Strengths
  • HepaGam B is a sterile solution of purified gamma globulin (5% or 50 milligrams per milliliter) that contains greater than 312 International Units per milliliter of anti-HBs.
  • The measured potency of each lot is stamped on the vial label.
  • To ensure that the label claim of >312 International Units per milliliter is maintained over the product shelf life, a higher potency of 550 International Units per milliliter is targeted at the time of manufacture.
    • This higher target potency is a manufacturing requirement to account for variability in the potency assay and changes in potency over time.
    • The potency assay has a relative standard deviation (RSD) of approximately 10%.
    • The actual potency test result may vary from approximately 400 to 700 International Units per milliliter (3x RSD) based on statistical assessment of manufactured lots with a target potency of 550 International Units per milliliter.
  • Calculate the dosing for the prevention of hepatitis B recurrence following liver transplantation from the measured potency of the particular lot of HepaGam B as stamped on the vial label.
How Supplied

NDC 70257-053-51; a carton containing a 1.0 milliliter single dose vial (>312 IU per milliliter; measured potency of each lot is stamped on the vial label) and a package insert.

NDC 70257-054-51; a carton containing a 5.0 milliliter single dose vial (>312 IU per milliliter; measure potency of each lot is stamped on the vial label) and a package insert.

Distributed by: Saol Therapeutics Inc., Roswell, GA 30076, U.S. License No. 2098

Drugs

Drug Countries
HEPAGAM B Canada, Israel, Turkey, United States

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