Cangene
Hepatitis B Immune Globulin (Human) – HepaGam B
Status: marketed in U.S.
Organizations involved:
Cangene Corp. – R&D; Tech.; USA mark.;
Apotex Inc. – Parent
Nabi Biopharmaceuticals – Former
New York Blood Center – Tech.
Cross ref.: See the entry for Hepatitis B Immune Globulin, i.v./Nabi or Nabi-HB (#756) formerly manufactured by Cangene. See the other Hepatitis B Immune Globulin entries and the Immune Globulin Products entry (#743). See the entries for Hepatitis B Immune Globulin Products (#751) and Immune Globulin Products (#743). See also the other hepatitis B virus immune globulin products. See the Hepatitis B Vaccine Products entry (#468) for background about hepatitis B virus and chronic hepatitis B.
Description: HepaGam B is an aqueous solvent/detergent-treated sterile solution of purified gamma globulin (IgG) fraction of human plasma containing polyclonal antibodies to hepatitis B surface antigen inactivated by the solvent-detergent method and nanofiltered for virus removal. It is prepared from plasma donated by healthy, screened donors with high titers of hepatitis B virus (HBV) surface antigen (HBsAg) antibodies and purified by an anion-exchange column chromatography manufacturing method, for administration by for intramuscular injection.
HepaGam B is formulated as a 5% (50 mg/mL) protein solution with 10% maltose and 0.03% polysorbate 80 (Tween 80) at pH 5.6. It is packaged in 1 mL and 5 mL single dose vials. The product appears as a clear to opalescent liquid. HepaGam B contains no preservatives and is intended for single use by the intramuscular (i.m.) route only. Potency is expressed in international units (IU) by comparison to the World Health Organization (WHO) standard Hepatitis B Immune Globulin. The potency of each vial of HepaGam B exceeds the potency of hepatitis B virus antibodies in the U.S. reference hepatitis B immune globulin (FDA). The U.S. reference has been tested against the WHO standard and is equal to 220 IU/mL.
HepaGam B is packaged in single dose 1.0 mL vials and 5.0 mL single dose vials, each containling > 312 IU/mL. The dating period is 36 months from the date of manufacture when stored at 2 - 8 oC. The date of manufacture is defined as the date of the [redacted/censored by FDA] filtration of the finished bulk product. The product is stored at 2-8 °C (refrigerated).
Nomenclature: Hepatitis B Immune Globulin, i.m./Cangene [BIO]; hepatitis B immune globulin (Human) [FDA]; HepaGam B [TR]
Companies.: Cangene Corp. (originally Rh Pharmaceuticals, Inc.), CBER/FDA est. no. 1201, developed and manufactures the product at its facilities in Winnepeg, Manitoba, Canada. Apotex Holdings Inc., a major Canadian generic drug company, is majority shareholder (82%) in Cangene, distributed HepaGam B in the U.S. and Canada.
Cangene formerly manufactured a hepatitis B immune globulin product (Nabi-HB) for Nabi, which has built its own manufacturing facilities and now manufactures its own product (see #755).
In Oct. 2009, Cangene acquired all U.S. commercialization rights for HepaGam.
Manufacture: The source plasma used in the manufacture is tested using an FDA-licensed Nucleic Acid testing (NAT; PCR) assay for HIV-1 and HCV and found to be negative. An investigational NAT for HBV is performed on all Source Plasma used, and found to be negative. However, the significance of a negative result has not been established. Plasma also is tested by in-process NAT for hepatitis A virus (HAV) and parvovirus B19 (B19) via minipool testing. The limit for B19 in the manufacturing pool is set not to exceed 104 IU of B19 DNA per mL.
The manufacturing process contains two steps specifically for virus clearance. The solvent detergent viral inactivation step [using tri-n-butyl phosphate (TNBP) and octoxynol (Triton X-100)] is effective in the inactivation of enveloped viruses, such as hepatitis B, hepatitis C and HIV. Virus nanofiltration, using a Planova 35 nm virus filter, is effective for the removal of viruses based on their size, including some non-enveloped viruses. Also, anion-exchange chromatography contributes to the overall viral clearance capacity for small non-enveloped viruses.
FDA class: Biologic BLA
Approvals: Date = 20060127; original BLA (125035/0); Indications: = treatment following acute exposure to blood containing HBsAg, perinatal exposure of infants born to hepatitis B virus surface antigen (HBsAg)-positive mothers, sexual exposure to HBsAg-positive persons, and household exposure to persons with acute hepatitis B virus infection
Date = 20070406; BLA supplement; Indications: = approval for the prevention of Hepatitis B recurrence following liver transplantation in HBsAg-positive liver transplant patients
Indications: [full text of the "INDICATIONS AND USAGE” section of product insert/labeling, 4/2007]:
1.1 Prevention of Hepatitis B recurrence following Liver Transplantation: HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), is indicated for the prevention of hepatitis B recurrence following liver transplantation, in HBsAg-positive liver transplant patients. HepaGam B should be administered intravenously for this indication.
1.2 Postexposure Prophylaxis: HepaGam B is indicated for the treatment of acute exposure to blood containing HBsAg, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg-positive
persons and household exposure to persons with acute HBV infection in the following settings:
Acute Exposure to Blood Containing HBsAg; Following either parenteral exposure (needlestick, bite, sharps), direct mucous membrane contact (accidental splash), or oral ingestion (pipetting accident), involving HBsAg-positive materials such as blood, plasma or serum.
Perinatal Exposure of Infants Born to HBsAg-positive Mothers: Infants born to mothers positive for HBsAg with or without HBeAg.
Sexual Exposure to HBsAg-positive Persons: Sexual partners of HBsAg-positive persons.
Household Exposure to Persons with Acute HBV Infection.
Infants less than 12 months old whose mother or primary caregiver is positive for HBsAg. Other household contacts with an identifiable blood exposure to the index patient.
HepaGam B is indicated for intramuscular use only for these post-exposure prophylaxis indications:.
Status: Cangene filed the BLA for its own hepatitis B immune globulin product in Sept. 2001 for post-exposure prevention of hepatitis B virus infection. Approval was granted on Jan. 27, 2006 (approval time = ~4.4 years).
On Jan. 19, 2007, HepaGam B received Notice of Compliance with conditions (“NOC/c”), type of approval, in Canada for the prevention of Hepatitis B recurrence following liver transplantation in adult patients with Hepatitis B who have no or low levels of hepatitis B virus replication. This confers approval in Canada, while requiring Cangene to continue with a confirmatory clinical study.
On April 6, 2007, HepaGam B received FDA approval to prevent hepatitis B recurrence following liver transplantation in hepatitis B virus surface antigen (“HBsAg”)-positive liver transplant patients, with orphan designation. HepaGam B is the first/only immune globulin appoved in the U.S. for this indication.
On March 17, 2010, the EU approved ImmunoGam for immunoprophylaxis of hepatitis B
Tech. transfer: Solvent detergent viral inactivation was developed by and nonexclusively licensed from the New York Blood Center. For example, see U.S. patent 4,820,805. See the entry for Pooled Plasma, Solvent Detergent Treated (SD Plasma) (#799) for further information about solvent detergent viral inactivation, used primarily for inactivation of enveloped viruses (e.g., HIV, hepatitis B and C viruses).
Medical: For hepatitis B prophylaxis in liver transplant patients, HepaGam B should be administered intravenously. For its other approved post-exposure prophylaxis (treatment) indications:, HepaGam B should be administered intramuscularly.
Market: The 2007 Average Wholesale Price (AWP) is $182.80/1 mL vial, and $800.00/5 mL vial (Red Book, 2007).
Apotex Corp. expanded distribution of HepaGam B in the U.S. by including it in Novation, LLC’s product line-up, making HepaGam B directly available to Novation’s nearly 2,500 member healthcare organizations in the U.S.
Index Terms:
Companies involvement:
Full monograph
755 Hepatitis B Immune Globulin, i.m./
Nomenclature:
Hepatitis B Vaccine, rDNA/Medeva [BIO]
Hepacare [TR]
Hepagene [TR former]
HBsAg, rDNA [SY]
hepatitis B virus vaccine, rDNA, triple antigen [SY]
FDA Class: Biologic
biopharmaceutical products
exempt from CBER lot release requirements
recombinant DNA
vaccines, subunit
vaccines, viral
exempt from CBER lot release requirements
hepatitis B virus (HBV)
hepatitis B virus (HBV)
mammalian cell culture
mumps virus Jeryl Lynn strain
murine monoclonal antibody, RFT5
virus culture
aluminum hydroxide
hepatitis B virus (HBV)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
FD&C Yellow 5
North American coral snake
North American coral snake
EU011 Approved Formerly in EU/withdrawn
UM999 Not Available/Not Marketed in US
US01 FDA application withdrawn or rejected
EM999 Not Available/Not Marketed in EU
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