Status: approved; marketed

Organizations involved:

Talecris Biotherapeutics Inc. – Manuf.; USA mark.

Instituto Grifols, S.A. – Parent

NPS Pharmaceuticals Inc – Former

Bayer Corp. – R&D; Tech.; Former

Bayer Schering Pharma AG – Intl. mark.; Parent

New York Blood Center, Inc. – Tech.

Cross ref: See the entries for Hepatitis B Immune Globulin Products (#751) and Immune Globulin Products (#638). 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: HyperHEP B S/D (formely BayHep B) is an aqueous formulation of Hepatitis B Immune Globulin (Human) or immune globulin with a high titer of hepatitis B virus (HBV) antibodies prepared from fractionated pooled blood Plasma obtained from donors with high titers of antibodies to hepatitis B virus surface antigen (HBsAg; donors having received vaccination with one of the two approved hepatitis B virus vaccines). HyperHEP B S/D manufacture includes solvent detergent viral inactivation, and two heat (pasteurization) treatments steps. HyperHEP B S/D contains 15-18% protein, > 80% monomeric (non-polymerized) IgG, at pH of 6.4-7.2 in 0.21-0.32 M glycine.

HyperHEP B S/D is packaged in 0.5 ml single-dose syringes for use in newborn infants; in 1 ml single-dose syringes; and in 5 ml multi-dose vials. HyperHEP B S/D contains HBsAg antibodies greater than or equal to the potency of HBsAg antibodies in the U.S. reference standard for Hepatitis B Immune Globulin (Human) maintained by CBER, FDA. This U.S. reference standard has been tested against the World Health Organization (WHO) standard Hepatitis B Immune Globulin and shown to contain 217 International Units (IU) per mL. HyperHEP B S/D contains no preservatives. IgA is present at 0.1-1 mg/ml. Excipients include 0.21-0.32 M glycine and sodium carbonate for pH adjustment. Plasma used for concentration adjustment is obtained from lots of pooled plasma from only 100 or fewer donors (a relatively small pool). HyperHEP B S/D should be stored at 2-8˚C (refrigerated), and has a shelf life of 36 months.

Nomenclature: Hepatitis B Immune Globulin/Talecris [BIO]; HyperHEP B S/D [TR]; BayHep B [TR former]; Hepatitis B Immune Globulin (Human) [FDA]; HyperHep [TR]; NDC 00026-0636-00, NDC 00026-0636-01, NDC 00026-0636-05 [NDCs for BayHep B]; NDC 13533-636-03, NDC 13533-636-02, NDC 13533-636-01, NDC 13533-636-05 [NDC for HyperHEP B]

Companies.: BayHep B was developed and originally manufactured by Bayer Corp., now Bayer Schering Corp. (Berkeley, CA; formerly Miles Labs.; before that Cutter Labs.), CBER/FDA est. no. 0003. It was marketed in the U.S. by Bayer Corp., and internationally by Bayer AG.

In April 2005, Talecris Biotherapeutics Inc., a subsidiary of NPS Pharmaceuticals Inc., acquired the blood/plasma products business of Bayer, including manufacturing and U.S marketing, with Bayer AG, now Bayer Schering Pharma AG, retaining international marketing.

In Feb. 2011, Grifols S.A./Instituto Grifols acquired Talecris Biotherapeutics.

Manufacture: The immune globulin is isolated by conventional Cohn cold ethanol fractionation of pooled human plasma from persons having received hepatitis B virus vaccine. The immune globulin is isolated from Cohn Fraction II. The fraction II solution is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate (for solvent detergent viral inactivation), and is heated and maintained at 30˚C for at least six hours (for further viral inactivation). The reactants are removed by precipitation, filtration, ultrafiltration, and diafil-tration. HyperHEP B S/D is packaged in final containers and heated and maintained at 20-27˚C for 21-28 days (for further viral inactivation). In April 2003, Bayer announced that HyperHEP B S/D manufacturing processes “successfully inactivate vaccinia,” eliminating the risk of vaccinia virus infection from plasma donors having received smallpox virus vaccination.

FDA class: Biologic PLA

CBER class: Blood And Blood Derivatives

Approvals: Date = 19770923 [also reported as 19740612]; approval of HyerHep (no longer marketed)

Date = 19960800 (exact date unknown); supplemental approval, apparently for BayHep B, with addition of a solvent/detergent viral inactivation step during manufacture

Indications: for post-exposure prophylaxis against hepatitis B virus infection following either parenteral exposure, direct mucous membrane contact, sexual exposure or oral ingestion involving hepatitis B virus-containing (hepatitis B surface antigen-positive) biological fluids, usually occupational exposures, e.g., needle sticks, among health care professionals and researchers; also for prophylaxis in infants born to hepatitis B virus infected (hepatitis B surface antigen-positive) mothers

Tech. transfer: Solvent detergent viral inactivation technology 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 for inactivation of enveloped viruses (e.g., HIV, hepatitis B and C viruses).

Market: The 2007 Average Wholesale Price (AWP) is $75.60/0.5 mL neonatal prefilled syringe; $145.56/1 mL vial neonatal syringe, $142.56/1 mL single-dose prefilled syringe, and $684.00/5 mL vial (Red Book, 2007).

In its March 22, 2006 price list, FFF Enterprises, a major biologics distributor, reported its price as $58.50/prefilled 0.5 mL safety syringe; $108.50/1 mL syringe; and $505.00/5 mL vial.