DESCRIPTION
Immune Globulin Intravenous (Human), 10% -- Gamimune® N, 10% treated with solvent/detergent is a sterile solution of human protein containing no preservative. Gamimune N, 10% consists of 9%-11% protein in 0.16-0.24 M glycine. Not less than 98% of the protein has the electrophoretic mobility of gamma globulin. Not less than 90% of the IgG is monomer. Also present are traces of IgA and of IgM. The distribution of IgG subclasses is similar to that found in normal serum. The measured buffer capacity is 35 mEq/L and the osmolality is 274 mOsmol/kg solvent.
The product is made by cold ethanol fractionation of large pools of human plasma. Part of the fractionation may be performed by another licensed manufacturer. The immunoglobulin is isolated from Cohn Effluent III after limited diafiltration and ultrafiltration. The solution is adjusted to 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate. After addition of the solvent (TNBP) and the 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 diafiltration and ultrafiltration. The protein is stabilized during the process by adjusting the pH of the solution to 4.0-4.5. 1 Isotonicity is achieved by the addition of glycine. Gamimune N, 10% treated with solvent/detergent is then incubated in the final container (at the low pH of 4.25), for a minimum of 21 days at 20°C. The product is intended for intravenous administration.
The removal and inactivation of spiked model enveloped and non-enveloped viruses during the manufacturing process for Gamimune N, 10% 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 for Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model for Hepatitis B 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 seen between the Fraction II + IIIW and Effluent III steps and between the Effluent III and Filtrate III steps. Significant inactivation of enveloped viruses is achieved at the time of treatment of Filtrate III with TNBP/sodium cholate and also at the time of low pH incubation in the final container.
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