Bivigam

Bivigam
Immune Globulin Intravenous (Human), 10% Liquid

WARNING

ACUTE RENAL DYSFUNCTION AND ACUTE RENAL FAILURE

Use of Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death1,2. Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs (see WARNINGS AND PRECAUTIONS).

Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. BIVIGAM does not contain sucrose.

For patients at risk of renal dysfunction or failure, administer BIVIGAM at the minimum dose recommended and the minimum infusion rate practicable (see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS).

DRUG DESCRIPTION

BIVIGAM is a purified, sterile, ready-to-use preparation of concentrated human immunoglobulin G (IgG) antibodies. The distribution of IgG subclasses is similar to that of normal plasma.19,20 The active ingredient is human immunoglobulin purified from source human plasma and processed using a modified classical Cohn Method 6 / Oncley Method 9 fractionation procedure. BIVIGAM contains 100 ± 10 mg/mL protein, of which not less than 96% is human immunoglobulin obtained from source human plasma. It is formulated in water for injection containing 0.100-0.140 M sodium chloride, 0.20-0.29 M glycine, 0.15–0.25% polysorbate 80, and pH 4.0–4.6. BIVIGAM contains ≤ 200 μg/mL of IgA.

Each plasma donation used for the manufacture of BIVIGAM is collected from FDA licensed facilities and undergoes rigorous testing. Plasma donations must test negative for hepatitis B virus (HBV) surface antigen (HBsAg), antibodies to human immunodeficiency virus (HIV) strains 1 and 2 (anti-HIV-½), and antibodies to the hepatitis C virus (anti-HCV) as determined by enzyme immuno assay (EIA). In addition, each plasma unit must test negative and/or non-reactive for HIV RNA, HCV RNA, HBV DNA, Hepatitis A Virus (HAV) RNA, and Parvovirus B19 (B19 virus) DNA as determined by Nucleic Acid Amplification Testing (NAT) of plasma minipools. NAT for B19 virus DNA is also performed on a sample of the manufacturing pool and the limit for B19 virus DNA in a manufacturing pool is set not to exceed 104 IU/mL.

The manufacturing process of BIVIGAM employs three steps to remove/inactivate adventitious viruses to minimize the risk of virus transmission. The steps are “Precipitation and removal of fraction III” during cold ethanol fractionation, classical “Solvent/detergent treatment” and “35 nm virus filtration”. In compliance with current guidelines, the steps have been separately validated in a series of in vitro experiments for their capacity to inactivate or remove both enveloped and non-enveloped viruses.

Precipitation and removal of fraction III removes both enveloped and non-enveloped viruses, solvent/detergent treatment represents a virus inactivation step for enveloped viruses, and 35 nm virus filtration removes both enveloped and non-enveloped viruses by size exclusion. In addition to the steps above, low pH during several steps of the production process contributes to virus inactivation. The results of virus validation studies for BIVIGAM are shown in Table 3, expressed as log10 reduction factors.

Table 3: Virus Validation Data for BIVIGAM

Virus Type Family Virus Removal/Inactivation (log10)
Enveloped viruses Non-enveloped viruses
Retro Flavi Herpes Picorna Parvo Polyoma
Step/Virus HIV BVDV SinV WNV PRV MEV BPV PPV SV40
Precipitation and Removal of Fraction III and Depth Filtration -- 1.87* -- -- -- 5.29 -- 4 2.00*
TNBP/Triton X-100 Treatment > 4.43 5.04 > 7.11 > 4.96 > 4.01 -- -- -- --
35 nm Virus Filtration > 5.19 > 4.88 -- -- > 4.64 < 1.0 6.18 < 1.0 > 5.02
Total Clearance > 9.62 > 11.79 > 7.11 > 4.96 > 8.65 5.29 6.18 4 > 7.02
* without depth filtration -- not done values below 1 log10 are considered as insignificant and are not used for total clearance; HIV, human immunodeficiency virus; BVDV, Bovine viral diarrhea virus, model virus for HCV; SinV, Sindbis virus, model virus for HCV; WNV, West Nile virus; PRV, Pseudorabies virus, model virus for herpes viruses and Hepatitis B virus; MEV, Murine encephalomyelitis virus, model virus for hepatitis A virus; BPV, Bovine parvovirus, model virus for human B19 virus; PPV, Porcine parvo virus, model virus for human B19 virus; SV40, Simian virus 40, model virus for highly resistant non- enveloped viruses.

REFERENCES

1. Gupta N, Ahmed I, Nissel-Horowitz S, Patel D, Mehrotra B. Intravenous gammaglobulin-associated acute renal failure. Am J Hematol 2001; 66:151-152.

2. Cayco, A.V., M.A. Perazella, and J.P. Hayslett. Renal insufficiency after intravenous immune globulin therapy: a report of two cases and an analysis of the literature. J Am Soc Nephrol 1997; 8:1788-1794.

19. Skvaril F. Qualitative and quantitative aspects of IgG subclasses in i.v. immunoglobulin preparations. In: Nydegger UE, ed. Immunotherapy. London: Academic Press; 1981:118-122.

20. French M. Serum IgG subclasses in normal adults. Monogr Allergy 1986, 19:100-107.

Last reviewed on RxList: 1/28/2013
This monograph has been modified to include the generic and brand name in many instances.

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