Rhogam Ultra-Filtered Plus
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Rhogam Ultra-Filtered Plus
RhoGAM® Ultra-Filtered PLUS (rhod immune globulin human)
(300 µg Rho(D) Immune Globulin [Human]) (1500 IU)
MICRhoGAM® Ultra-Filtered PLUS (rhod immune globulin human)
(50µg Rho(D) Immune Globulin [Human]) (250 IU)
For Intramuscular Injection Only
Prefilled syringes, preservative-free (thimerosal free), latex-free delivery system
RhoGAM and MICRhoGAM Rho(D) Immune Globulin (Human) are sterile solutions containing immunoglobulin G (IgG) anti-D (anti-Rh) for use in preventing Rh immunization. They are manufactured from human plasma containing anti-D. A single dose of RhoGAM contains sufficient anti-D (300 µg or 1500 IU) to suppress the immune response to up to 15 mL of Rh-positive red blood cells.4,15 A single dose of MICRhoGAM contains sufficient anti-D (50 µg or 250 IU) to suppress the immune response to up to 2.5 mL of Rh-positive red blood cells. The anti-D dose is measured by comparison to the RhoGAM in-house reference standard, the potency of which is established relative to the U.S./World Health Organization/European Pharmacopoeia Standard Anti-D Immunoglobulin Rho(D) Immune Globulin (Human) CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule).16
Plasma for RhoGAM is typically sourced from a donor center owned and operated by Ortho-Clinical Diagnostics. All donors are carefully screened by history and laboratory testing to reduce the risk of transmitting blood-borne pathogens from infected donors. Each plasma donation is tested and found to be non-reactive for the presence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C (HCV) and human immunodeficiency viruses (HIV) 1 and 2. Additionally, plasma is tested by FDA licensed Nucleic Acid Testing (NAT) for HCV and HIV-1 and the results must be negative. Plasma is also tested by investigational NAT for hepatitis B (HBV) and must be non-reactive. However, the significance of a negative result has not been established. Plasma is tested by NAT for hepatitis A virus and parvovirus B19.
Fractionation of the plasma is performed by a modification of the cold alcohol procedure that has been shown to significantly lower viral titers.10 Following plasma fractionation, a viral clearance filtration step and a viral inactivation step are performed. The viral filtration step removes viruses via a size-exclusion mechanism utilizing a patented Viresolve 180 ultrafiltration membrane with defined pore-size distribution of 12-18 nanometers to remove enveloped and non-enveloped viruses. Following viral filtration, quality control tests (CorrTest and diffusion test) are performed on the Viresolve 180 ultrafiltration membrane to insure filter integrity.17 The viral inactivation step utilizes Triton X-100 and tri-n-butyl phosphate (TNBP) to inactivate enveloped viruses such as HCV, HIV and West Nile Virus (WNV)10,18 (Patent Pending).
The donor selection process, the fractionation process, the viral filtration step and the viral inactivation process increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. Rho(D) Immune Globulin (Human) intended for intramuscular use and prepared by cold alcohol fractionation has not been shown to transmit hepatitis or other infectious diseases.19 There have been no documented cases of infectious disease transmission by RhoGAM or MICRhoGAM.
Laboratory spiking studies10,20 have shown that the cumulative viral removal and inactivation capability of the RhoGAM / MICRhoGAM manufacturing process is as follows:
|Fractionation||> 7.98||7.29||> 11.74||8.30||ND||ND||ND|
|Viral Filtration||> 5.60||5.40||> 6.20||3.30||4.16||ND||> 5.07|
|Viral Inactivation||> 4.28||> 4.90||> 5.58||N/A||N/A||> 7.05||N/A|
|Total Viral Reduction||> 17.86||> 17.59||> 23.52||11.60||4.16||> 7.05||> 5.07|
| Units = log10 reduction
HIV Human Immunodeficiency Virus, Model for HIV-1 and 2 and Human T-cell Lymphotropic Virus (HTLV) 1 and 2
BVDV Bovine Viral Diarrhea Virus, Model for Hepatitis C Virus
PRV Pseudorabies Virus, Model for Herpes Viruses
PPV Porcine Parvovirus, Model for Parvovirus B19
EMC Encephalomyocarditis Virus, Model for Hepatitis A Virus
WNV West Nile Virus
HAV Hepatitis A Virus
ND Not Determined
N/A Not Applicable
The safety of Rho(D) Immune Globulin (Human) has been further shown in an empirical study of viral marker rates in female blood donors in the United States.21 This study revealed that Rh-negative donors, of whom an estimated 55-60% had received Rho(D) Immune Globulin (Human) for pregnancy-related indications, had prevalence and incidence viral marker rates similar to those of Rh-positive female donors who had not received Rho(D) Immune Globulin (Human).
The final product contains 5 ± 1% IgG, 2.9 mg/mL sodium chloride, 0.01% Polysorbate 80 (non-animal derived) and 15 mg/mL glycine. Small amounts of IgA, typically less than > 15 µg per dose, are present.10 The pH range is 6.20 - 6.55 and IgG purity is 98%. The product contains no added human serum albumin (HSA), no thimerosal or other preservatives and utilizes a latex-free delivery system.
4 Pollack W, Ascari WQ, Crispen JF, O'Connor RR, Ho TY. Studies on Rh prophylaxis. II. Rh immune prophylaxis after transfusion with Rh-positive blood. Transfusion 1971;11:340-44.
15 Pollack W, Ascari WQ, Kochesky RJ, O'Connor RR, Ho T Y, Tripodi D. Studies on Rh prophylaxis. I. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 1971;11:333-39.
16 Thorpe SJ, Sands D, Fox B, Behr-Gross ME, Schaffner G, Yu MW. A global standard for anti-D immunoglobulin: international collaborative study to evaluate a candidate preparation. Vox Sang 2003;85:313-21.
17 Phillips MW, DiLeo AJ. A Validatible Porosimetric Technique for verifying the integrity of virus-retentive membranes. Biologicals 1996;24:243-53.
18 Horowitz B, Wiebe ME, Lippin A, Stryker MH. Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri (n-butyl) phosphate detergent combinations. Transfusion 1985; 25(6):516-22.
19 Tabor E. The epidemiology of virus transmission by plasma derivatives: clinical studies verifying the lack of transmission of hepatitis B and C viruses and HIV type 1. Transfusion 1999;39:1160-68.
20 Van Holten RW, Ciavarella D, Oulundsen G, Harmon F, Riester S. Incorporation of an additional viral-clearance step into a human immunoglobulin manufacturing process. Vox Sang 2002;83:227-33.
21 Watanabe KK, Busch MP, Schreiber GB, Zuck TF. Evaluation of the safety of Rh Immunoglobulin by monitoring viral markers among Rh-negative female blood donors. Vox Sang 2000;8:1-6.
22 Crispen J. Immunosuppression of small quantities of Rh-positive blood with MICRhoGAM in Rh-negative male volunteers. In: Proceedings of a symposium on Rh antibody mediated immunosuppression. Raritan, NJ: Ortho Research Institute of Medical Sciences, 1975:51-54.
23 Bowman JM, Chown B, Lewis M, Pollock JM. Rh isoimmunization during pregnancy: antenatal prophylaxis. Can Med Assoc J 1978;118:623-27.
24 Bowman JM, Pollock JM. Antenatal prophylaxis of Rh isoimmunization: 28-weeks' gestation service program. Can Med Assoc J 1978;118:627-30.
25 Stewart FH, Burnhill MS, Bozorgi N. Reduced dose of Rh immunoglobulin following first trimester pregnancy termination. Obstet Gynecol 1978;51:318-22.
26 Pollack W, Gorman JG, Freda VJ, Ascari WQ, Allen AE, Baker WJ. Results of clinical trials of RhoGAM in women. Transfusion 1968;8:151-53.
27 Freda VJ, Gorman JG, Pollack W, Bowe E. Prevention of Rh hemolytic disease - ten years' clinical experience with Rh immune globulin. New Engl J Med 1975; 292:1014-16.
Last reviewed on RxList: 5/9/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Rhogam Ultra-Filtered Plus Information
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