GAMMAPLEX Solution for infusion Ref.[27467] Active ingredients: Immunoglobulins, normal human, IV

GAMMAPLEX 10% is a ready to use sterile solution of polyclonal human Immunoglobulin G for intravenous administration that contains glycine and polysorbate 80 as stabilizers. Specifically, GAMMAPLEX 10% contains approximately 10 g normal human immunoglobulin and 200-300 mM glycine in 100 mL of buffer solution containing: <30 mM acetate, <30 mM sodium chloride and 1-6 mg polysorbate 80. Immunoglobulin G purity is ≥98%, the pH is in the range of 4.9 to 5.3, and osmolality is not less than 240 mOsmol/kg (typically 280 mOsmol/kg). The distribution of the four IgG subclasses reflects that of normal plasma. The content of IgA is less than 20 micrograms/mL. The anti-D and anti-A/anti-B hemagglutinin content of the drug product is strictly controlled to specification.

GAMMAPLEX 10% contains no reducing carbohydrate stabilizers (e.g. sucrose, maltose) and no preservative.

GAMMAPLEX 10% is prepared from large pools of human plasma by a combination of cold ethanol fractionation and ion exchange chromatography. Fab functions tested include antigen binding activity, and Fc functions tested include complement activation and rubella antibody-mediated hemolysis.

GAMMAPLEX 10% is manufactured from plasma, obtained from healthy US donors, who have passed viral screening tests. All donors are subjected to medical examinations, laboratory tests, and a review of their medical history before being allowed to donate blood or plasma.

All plasma donations are screened for antibody to HIV-1/2 and hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg). Additional testing of donations is carried out in plasma mini-pools (512 donations per pool) that undergo nucleic acid amplification testing (NAT) for HIV, hepatitis B virus (HBV), HCV, hepatitis A virus (HAV) and parvovirus B19.

Further testing is carried out on the manufacturing pools for HBsAg, and antibody to HIV-1/2; HCV and parvovirus B19 are also tested by NAT, with the limit for B19 set to not exceed 10 ⁴ IU B19 DNA per mL plasma.

There are three processing steps specifically designed to remove or inactivate viruses:

1. Solvent/Detergent treatment is targeted to enveloped viruses;
2. A virus filtration step designed to remove small viruses including non-enveloped viruses, on a size exclusion basis; and
3. The terminal low pH incubation step is identified as contributing to the overall viral clearance capacity for enveloped and non-enveloped viruses.

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. Overall virus reduction was calculated only from steps that were mechanistically independent from each other.

In addition, each step was validated to provide robust virus reduction. Table 5 presents the contribution of each process step to virus reduction and the overall process reduction.

Table 5. Viral Reduction by Process Step:

HIV: Human immunodeficiency virus
SIN: Sindbis virus, model for hepatitis C virus (HCV)
WNV: West Nile Virus
BVDV: Bovine viral diarrhea virus, model for HCV
IBR: Infectious bovine rhinotracheitis, bovine herpes virus model for enveloped DNA viruses including hepatitis B
HAV: Hepatitis A virus
EMC: Encephalomyocarditis, model for HAV
CPV: Canine parvovirus, model for human parvovirus B19
NA: Not applicable, solvent detergent step is limited to the inactivation of enveloped viruses
I: Inactivation by the product intermediate precluded the accurate estimation of the removal of these viruses by the filtration step
NT: Not tested
B19: Viral clearance of human parvovirus B19 was investigated experimentally at the 20 nm filtration step. The estimated Log reduction Factor obtained was 6.0