RhoGAM and MICRhoGAM Rh_o(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 Rh_o(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. Rh_o(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 studies^10,20 have shown that the cumulative viral removal and inactivation capability of the RhoGAM / MICRhoGAM manufacturing process is as follows:

The safety of Rh_o(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 Rh_o(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 Rh_o(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.