Status: approved; marketed

Organizations involved:

Talecris Biotherapeutics Inc. – Manuf.; R&D; Tech.; USA mark.

Instituto Grifols, S.A. – Parent

NPS Pharmaceuticals Inc – Former

Bayer Corp. – Former

Bayer Schering Pharma AG – Intl. mark.

New York Blood Center, Inc. – Tech.

Cross ref: See the entries for Rho(D) Immune Globulin Products (#776) and Immune Globulin Products (#743).

Description: HyperRHO S/D (formerly BayRho-D) is an aqueous formulation of Rho(D) Immune Globulin (Human) or immune globulin containing high titers of Rho(D) antigen-neutralizing antibodies obtained from fractionated pooled Plasma from donors with high levels of Rho(D) antibodies, generally from vaccination with Rho(D)-positive cells. manufacture includes solvent detergent treatment and two heat (pasteurization) treatment steps for viral inactivation. BayRho has been thimerosal-free since 1991.

HyperRHO S/D Full Dose is packaged in single full dose vials or syringes containing approximately 300 µg of Rho(D) antibodies for intramuscular injection, sufficient to effectively suppress the immunization potential of 15 mL of Rho(D) positive red blood cells; and syringes containing 50 µg of Rho(D) antibodies. HyperRHO S/D Full Dose is a 15-18% protein solution (primarily IgG) at pH of 6.4-7.2 in 0.21-0.32 M glycine. The product contains no preservatives and is stored at 2-8˚C (refrigerated).

HyperRHO S/D Mini Dose is the same product at the Full Dose product, but containing greater than or equal to one-sixth dosage (1 mL of Full Dose). Prefilled syringes hold 0.17 mL, ~50 µg of Rho(D) antibodies. One mini-dose is sufficient to suppress the immunizing potential of 2.5 mL of Rho(D) positive packed Red Blood Cells or the equivalent 5 mL of whole blood. This product is used for treating women at the time of spontaneous or induced abortion for embryos less than 12 weeks gestation, presuming the woman is RhoD-negative, not already sensitized to RhoD, and the father is not known to be RhoD-negative. It need not be used, if the fetus is RhoD-negative.

Nomenclature: Rho(D) Immune Globulin/Talecris [BIO]; HyperRHO S/D [TR]; BayRho-D [TR former]; Rho(D) Immune Globulin (Human) [FDA]; Rho(D) Immune Globulin [USAN]; Rho(D) Immune Human Globulin [former USAN]; Rho(D) Immune Globulin USP [USP]; NDC 0026-0631-01; NDC 0026-0631-10; NDC 0026-0631-15; NDC 0026-0631-22; NDC 0026-0631-06 [NDC]

Companies.: BayRho-D was developed and manufactured by Bayer Corp., FDA CBER est. no. 0008, a subsidiary of Bayer AG, at facilities in Clayton, NC. It was marketed in the U.S. by Bayer Corp., and internationally by Bayer AG affiliates. In April 2005, Talecris Biotherapeutics Inc., CBER/FDA est. no. 1716, a subsidiary of NPS Pharmaceuticals Inc., acquired the blood/plasma products business of Bayer AG, 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: Immune globulin is isolated by conventional Cohn cold ethanol fractionation of pooled human plasma selected for high levels of D antibodies. 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; solvent) and 0.2% sodium cholate (detergent) for 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 diafiltration. HyperRHO S/D Full Dose 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 Gamimune 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 = 19710611; first approval, PLA

Indications: [full text of the "INDICATIONS AND USAGE” section from HyperRHO S/D Full Dose insert/labeling, 7/22/2007]:

HyperRHO S/D Full Dose is recommended for the prevention of Rh hemolytic disease of the newborn by its administration to the Rho(D) negative mother within 72 hours after birth of an Rho(D) positive infant, providing the following criteria are met: 1. The mother must be Rho(D) negative and must not already be sensitized to the Rho(D) factor. 2. Her child must be Rho(D) positive, and should have a negative antiglobulin test (see PRECAUTIONS). If HyerRHO S/D Full Dose is administered antepartum, it is essential that the mother receive another dose of HyperRHO S/D Full dose after delivery of the RHo(D) positive infant. If the father can be determined to be Rho(D) negative, HyperRHO S/D Full Dose need not be given.

HyperRHO S/D Full Dose should be administered within 72 hours to all nonimmunized Rho(D) negative women who have undergone spontaneous or induced abortion, following ruptured tubal pregnancy, amniocentesis or abdominal trauma unless the blood group of the fetus or the father is known to be Rho(D) negative. If the fetal blood group cannot be determined, one must assume that it is Rho(D) positive, and HyperRHO S/D Full Dose should be administered to the mother.

Transfusion: HyperRHO S/D Full Dose may be used to prevent isoimmunization in Rho(D) negative individuals who have been transfused with Rho(D) positive red blood cells or blood components contain red blood cells.

Tech. transfer: Solvent detergent viral inactivation technology was developed by and nonexclusively licensed from the New York Blood Center, e.g., U.S. patent 4,820,805. See 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).

Market: The 2007 Average Wholesale Price (AWP) for BayRho D Full Dose is $105.60/1 mL prefilled syringe (Red Book, 2007). The 2007 AWP for BayRho-D Mini Dose is $366.00/package of ten 0.17 mL prefilled syringes. These prices are unchanged from 2004.

In its March 22, 2006 price list, FFF Enterprises, a major biologics distributor, reported $79.25/Full Dose 1 mL syringe and $265.95/10 Mini-Dose 0.17 mL syringes (no changes from 2004 or 2005).