Baygam (Immune Globulin Human) - Description and Clinical Pharmacology

DESCRIPTION

Immune Globulin (Human) -- BayGam® treated with solvent/detergent is a sterile solution of immune globulin for intramuscular administration; it contains no preservative. BayGam is prepared by cold ethanol fractionation from human plasma. The immune globulin is isolated from solubilized 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. After the addition of solvent (TNBP) and detergent (sodium cholate), the solution is heated to 30°C and maintained at that temperature for not less than 6 hours. After the viral inactivation step, the reactants are removed by precipitation, filtration and finally ultrafiltration and diafiltration. BayGam is formulated as a 15-18% protein solution at a pH of 6.4-7.2 in 0.21-0.32 M glycine. BayGam is then incubated in the final container for 21-28 days at 20-27°C.

The removal and inactivation of spiked model enveloped and non-enveloped viruses during the manufacturing process for BayGam has been validated in laboratory studies. Human Immunodeficiency Virus, Type 1 (HIV-1), was chosen as the relevant virus for blood products; Bovine Viral Diarrhea Virus (BVDV) was chosen to model Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model Hepatitis B virus and the Herpes viruses; and Reo virus type 3 (Reo) was chosen to model non-enveloped viruses and for its resistance to physical and chemical inactivation. Significant removal of model enveloped and non-enveloped viruses is achieved at two steps in the Cohn fractionation process leading to the collection of Cohn Fraction II: the precipitation and removal of Fraction III in the processing of Fraction II + IIIW suspension to Effluent III and the filtration step in the processing of Effluent III to Filtrate III. Significant inactivation of enveloped viruses is achieved at the time of treatment of solubilized Cohn Fraction II with TNBP/sodium cholate.

CLINICAL PHARMACOLOGY

Peak levels of immunoglobulin G are obtained approximately 2 days after intramuscular injection of BayGam. ¹ The half-life of IgG in the circulation of individuals with normal IgG levels is 23 days. ²

Passive immunization with BayGam modifies hepatitis A, prevents or modifies measles, and provides replacement therapy in persons with hypogammaglobulinemia or agammaglobulinemia. BayGam is not standardized with respect to antibody titers against hepatitis B surface antigen (HBsAg) and should not be used for prophylaxis of viral hepatitis type B. Prophylactic treatment to prevent hepatitis B can best be accomplished with use of Hepatitis B Immune Globulin (Human), often in combination with Hepatitis B Vaccine.³

BayGam may be of benefit in women who have been exposed to rubella in the first trimester of pregnancy and who will not consider a therapeutic abortion.⁴ BayGam may also be considered for use in immunocompromised patients for passive immunization against varicella if Varicella-Zoster Immune Globulin (Human) is not available. ⁵

Immune Globulin (Human) is not indicated for routine prophylaxis or treatment of rubella, poliomyelitis, mumps, or varicella. It is not indicated for allergy or asthma in patients who have normal levels of immunoglobulin.⁶

In a clinical study in eight healthy human adults receiving another hyperimmune immune globulin product treated with solvent/detergent, Rabies Immune Globulin (Human), BayRab®, prepared by the same manufacturing process, detectable passive antibody titers were observed in the serum of all subjects by 24 hours post injection and persisted through the 21 day study period. These results suggest that passive immunization with immune globulin products is not affected by the solvent/detergent treatment.