Gamunex (Immune Globulin Intravenous Human) - Description

DESCRIPTION

Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified, (GAMUNEX®) is a ready-to-use sterile solution of human immune globulin protein for intravenous administration. GAMUNEX® 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. GAMUNEX® contains trace levels of fragments and IgA (average 0.046 mg/mL). IgM levels were at or below the limit of quantitation (0.002 g/L). 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 258 mOsmol/kg solvent, which is close to physiological osmolality (285-295 mOsmol/kg). The pH of GAMUNEX® is 4.0-4.5. GAMUNEX® contains no preservative.

GAMUNEX® is made from large pools of human plasma by a combination of cold ethanol fractionation, caprylate precipitation and filtration, and anion-exchange chromatography. Two of the four ethanol fractionation steps of the Cohn-Oncley process have been replaced by tandem anion-exchange chromatography. The IgG proteins are not subjected to heating or chemical or enzymatic modification steps. Fc and Fab functions of the IgG molecule are retained, but do not activate complement or pre-Kallikrein activity in an unspecific manner. The protein is stabilized during the process by adjusting the pH of the solution to 4.0-4.5. Isotonicity is achieved by the addition of glycine. GAMUNEX® is incubated in the final container (at the low pH of 4.0-4.3), for a minimum of 21 days at 23° to 27°C. The product is intended for intravenous administration.

The capacity of the manufacturing process to remove and/or inactivate enveloped and non-enveloped viruses has been validated by laboratory spiking studies on a scaled down process model, using the following enveloped and non-enveloped viruses: human immunodeficiency virus, type I (HIV-1) as the relevant virus for HIV-1 and HIV-2; bovine viral diarrhea virus (BVDV) as a model for hepatitis C virus; pseudorabies virus (PRV) as a model for large DNA viruses (e.g. herpes viruses); Reo virus type 3 (Reo) as a model for non-enveloped viruses and for its resistance to physical and chemical inactivation; hepatitis A virus (HAV) as relevant non-enveloped virus, and porcine parvovirus (PPV) as a model for human parvovirus B19.

The following process steps contribute to virus inactivation and/or removal: caprylate precipitation/cloth filtration, caprylate incubation, column chromatography and final container low pH incubation. Caprylate is the basis of two mechanistically distinct virus clearance steps, the caprylate precipitation/cloth filtration step and the caprylate incubation step. During the caprylate precipitation/cloth filtration step, protein impurities and potential enveloped or non-enveloped viral contaminants are precipitated by caprylate and the precipitate is removed from the product stream by filtration through a cloth filter. In a subsequent step, enveloped viruses are inactivated during incubation with caprylate. The table below presents the contribution of each process step to virus reduction and the overall process reduction. Virus removal steps were evaluated independently and in combination to identify those steps, which were mechanistically distinct. Overall virus reduction was calculated only from steps that were mechanistically independent from each other and truly additive. In addition, each step was verified to provide robust virus reduction across the production range for key operating parameters.