DESCRIPTION
GAMMAGARD S/D, * Immune Globulin Intravenous (Human) [IGIV] is a solvent/detergent treated, sterile, freeze-dried preparation of highly purified immunoglobulin G (IgG) derived from large pools of human plasma. The product is manufactured by the Cohn-Oncley cold ethanol fractionation process followed by ultrafiltration and ion exchange chromatography. Source material for fractionation may be obtained from another U.S. licensed manufacturer. The manufacturing process includes treatment with an organic solvent/detergent mixture,1,2 composed of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80.3 The GAMMAGARD S/D manufacturing process provides a significant viral reduction in in vitro studies. 3 These studies, summarized in Table 1, demonstrate virus clearance during GAMMAGARD S/D manufacturing using infectious human immunodeficiency virus, Types 1 and 2 (HIV-1, HIV-2); bovine viral diarrhea virus (BVD), a model virus for hepatitis C virus; sindbis virus (SIN), a model virus for lipid-enveloped viruses; pseudorabies virus (PRV), a model virus for lipid-enveloped DNA viruses such as herpes; vesicular stomatitis virus (VSV), a model virus for lipid-enveloped RNA viruses; hepatitis A virus (HAV) and encephalomyocarditis virus (EMC), a model virus for non-lipid enveloped RNA viruses; and porcine parvovirus (PPV), a model virus for non-lipid enveloped DNA viruses. 3 These reductions are achieved through a combination of process chemistry, partitioning and/or inactivation during cold ethanol fractionation and the solvent/detergent treatment.3
*Manufactured under U.S. Patent No. 4,439,421
Copyright 1986, 1987, 1988, 1989, 1990, 1994, 1995, 1997, 1998, 1999, 2000, 2001 and 2002 Baxter Healthcare Corporation. All rights reserved.
TABLE 1
In Vitro Virus Clearance During GAMMAGARD S/D
Manufacturing
|
Process Step Evaluated
|
Virus Clearance (log10)
|
|
Lipid Enveloped Viruses
|
Non-Lipid Enveloped
Viruses
|
|
BVD
|
HIV-1
|
HIV-2
|
PRV
|
SIN
|
VSV
|
EMC
|
HAV
|
PPV
|
|
Step 1: Processing of Cryo-Poor Plasma to Fraction I+II+III Precipitate
|
0.6 * |
5.7
|
NT |
1.0 * |
NT |
NT |
NT |
0.5 * |
0.2 * |
|
Step 2: Processing of Resuspended Suspension A Precipitate to Suspension B Filter Press Filtrate
|
1.3
|
4.9
|
NT |
3.7
|
NT |
NT |
3.7
|
4.1
|
3.5
|
|
Step 3: Processing of Suspension B Filter Press to Suspension B Cuno 70 Filtrate
|
0.7 * |
4.0
|
NT |
4.5
|
NT |
NT |
3.0
|
3.9
|
3.9
|
|
Step 4: Solvent/Detergent Treatment
|
>4.9
|
>3.7
|
5.7
|
>4.1
|
5.1
|
6.0
|
NA |
NA |
NA |
|
Cumulative Reduction of Virus (log10)
|
6.2
|
18.3
|
5.7
|
12.3
|
5.1
|
6.0
|
6.7
|
8.0
|
7.4
|
*These values are not included in the computation of the cumulative reduction of virus since the virus clearance is within the variability limit of the assay (
NANot Applicable. Solvent/detergent treatment does not effect non-lipid enveloped viruses.
NT Not Tested.
|
|
When reconstituted with the total volume of diluent (Sterile Water for Injection, USP) supplied, this preparation contains approximately 50 mg of protein per mL (5%), of which at least 90% is gamma globulin. The product, reconstituted to 5%, contains a physiological concentration of sodium chloride (approximately 8.5 mg/mL) and has a pH of 6.8 ± 0.4. Stabilizing agents and additional components are present in the following maximum amounts for a 5% solution: 3 mg/mL Albumin (Human), 22.5 mg/mL glycine, 20 mg/mL glucose, 2 mg/mL polyethylene glycol (PEG), 1 µg/mL tri-n-butyl phosphate, 1 µg/mL octoxynol 9, and 100 µg/mL polysorbate 80. If it is necessary to prepare a 10% (100 mg/mL) solution for infusion, half the volume of diluent should be added, as described in the DOSAGE AND ADMINISTRATION section. In this case, the stabilizing agents and other components will be present at double the concentrations given for the 5% solution. The manufacturing process for GAMMAGARD S/D, isolates IgG without additional chemical or enzymatic modification, and the Fc portion is maintained intact. GAMMAGARD S/D contains all of the IgG antibody activities which are present in the donor population. On the average, the distribution of IgG subclasses present in this product is similar to that in normal plasma.3 GAMMAGARD S/D contains only trace amounts of IgA (
GAMMAGARD S/D, Immune Globulin Intravenous (Human) contains no preservative.
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