Prescription Drugs

CLINICAL PHARMACOLOGY Rh sensitization may occur in nonsensitized Rho(D) negative women following transplacental hemorrhage resulting from spontaneous or induced abortions.1-2 The risk of sensitization is higher in women undergoing induced abortions than in those aborting spontaneously.1-3 HyperRHO S/D Mini-Dose is used to prevent the formation of anti-Rho(D) antibody in Rho(D) negative women who are exposed to the Rho(D) antigen at the time of spontaneous or induced abortion (up to 12 weeks' gestation).3-5 HyperRHO S/D Mini-Dose suppresses the stimulation of active immunity by Rho(D) positive fetal erythrocytes that may enter the maternal circulation at the time of termination of the pregnancy. The amount of anti-Rho(D) in HyperRHO S/D Mini-Dose has been shown to effectively prevent maternal isosensitization to the Rho(D) antigens following spontaneous or induced abortion occurring up to the 12th week of gestation.6-8 After the 12th week of gestation, a standard dose of HyperRHO S/D Full Dose is indicated. In a clinical study in eight healthy human adults receiving another hyperimmune immune globulin product treated with solvent/detergent, Rabies Immune Globulin (Human), HyperRAB® S/D, prepared by the same manufacturing process, detectable passive antibody titers were observed in the serum of all subjects by 24 hours post injection and persisted through the 21 day study period. These results suggest that passive immunization with immune globulin products is not affected by the solvent/detergent treatment. REFERENCES 1. Queenan JT, Shah S, Kubarych SF, et al: Role of induced abortion in rhesus immunisation. Lancet 1(7704):815-7, 1971. 2. Goldman JA, Eckerling B: Prevention of Rh immunization after abortion with anti-Rho(D)-immuno globulin. Obstet Gynecol 40(3):366-70, 1972. 3. The selective use of Rho(D) immune globulin (RhIG). ACOG Tech Bull 61,1981. 4. Prevention of Rh sensitization. WHO Tech Rep Ser 468, 1971. 5. Recommendation of the Public Health Service Advisory Committee on Immunization Practices: Rh immune globulin. MMWR 21(15):126-7, 1972. 6. Stewart FH, Burnhill MS, Bozorgi N: Reduced dose of Rh immunoglobulin following first trimester pregnancy termination. Obstet Gynecol 51(3):318-22, 1978. 7. McMaster conference on prevention of Rh immunization. 28-30 September, 1977. Vox Sang 36(1):50-64, 1979. 8. Simonovits I: Efficiency of anti-D IgG prevention after induced abortion. Vox Sang 26(4):361-7, 1974.

CLINICAL PHARMACOLOGY HyperRHO S/D Full Dose is used to prevent isoimmunization in the Rho(D) negative individual exposed to Rho(D) positive blood as a result of a fetomaternal hemorrhage occurring during a delivery of an Rho(D) positive infant, abortion (either spontaneous or induced), or following amniocentesis or abdominal trauma. Similarly, immunization resulting in the production of anti-Rho(D) following transfusion of Rh positive red cells to an Rho(D) negative recipient may be prevented by admin istering Rho(D) Immune Globulin (Human).(5,6) Rh hemolytic disease of the newborn is the result of the active immunization of an Rho(D) negative mother by Rho(D) positive red cells entering the maternal circulation during a previous delivery, abortion, amniocentesis, abdominal trauma, or as a result of red cell transfusion.(7,8) HyperRHO S/D Full Dose acts by suppressing the immune response of Rho(D) negative individuals to Rho(D) positive red blood cells. The mechanism of action of HyperRHO S/D Full Dose is not fully understood. The administration of Rho(D) Immune Globulin (Human) within 72 hours of a full-term delivery of an Rho(D) positive infant by an Rho(D) negative mother reduces the incidence of Rh isoimmunization from 12%–13% to 1%–2%.(9) The 1%–2% treatment failures are probably due to isoimmunization occurring during the latter part of pregnancy or following delivery.(10) Bowman and Pollock(11) have reported that the incidence of isoimmunization can be further reduced from approximately 1.6% to less than 0.1% by administering Rho(D) Immune Globulin (Human) in two doses, one ante natal at 28 weeks' gestation and another following delivery. In a clinical study in eight healthy human adults receiving another hyperimmune immune globulin product treated with solvent/detergent, Rabies Immune Globulin (Human), HyperRAB® S/D, prepared by the same manufacturing process, detectable passive antibody titers were observed in the serum of all subjects by 24 hours post injection and persisted through the 21 day study period. These results suggest that passive immunization with immune globulin products is not affected by the solvent/detergent treatment. REFERENCES 5. Pollack W, Ascari WQ, Crispen JF, et al: Studies on Rh prophylaxis. II. Rh immune prophylaxis after transfusion with Rh-positive blood. Transfusion 11(6):340-4, 1971. 6. Keith LG, Houser GH: Anti-Rh immune globulin after a massive transfusion accident. Transfusion 11(3):176, 1971. 7. The selective use of Rho(D) immune globulin (RhIG). ACOG Tech Bull 61, 1981. 8. Current uses of Rho immune globulin and detection of antibodies. ACOG Tech Bull 35, 1976. 9. Pollack W: Rh hemolytic disease of the newborn: its cause and prevention. Prog Clin Biol Res 70:185-203, 1981. 10. Bowman JM, Chown B, Lewis M, et al: Rh isoimmunization during pregnancy: antenatal prophylaxis. Can Med Assoc J 118(6):623-7, 1978.

CLINICAL PHARMACOLOGY Mechanism of Action RhoGAM and MICRhoGAM act by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells. The mechanism of action is unknown. RhoGAM, MICRhoGAM and other Rho(D) Immune Globulin (Human) products are not effective in altering the course or consequences of Rh immunization once it has occurred. Obstetrical Use The Rh-negative obstetrical patient may be exposed to red blood cells from her Rh- positive fetus during the normal course of pregnancy or after obstetrical procedures or abdominal trauma. Use after Rh-Incompatible Transfusion An Rh-negative individual transfused with one unit of Rh-positive red blood cells has about an 80% likelihood of producing anti-D.4 However, Rh immunization can occur after exposure to < 1 mL of Rh-positive red blood cells. Protection from Rh immunization is accomplished by administering > 20 µg of RhoGAM or MICRhoGAM per mL of Rh-positive red blood cells within 72 hours of transfusion of incompatible red blood cells.13,22 Pharmacokinetic Properties Pharmacokinetic studies after intramuscular injection were performed on sixteen Rh-negative subjects receiving a single dose of (368 µg or 1840 IU) RhoGAM.10 Plasma anti-D levels were monitored for thirteen weeks using a validated Automated Quantitative Hemagglutination method with sensitivity of approximately 1 ng/mL. The following mean pharmacokinetic parameters were obtained from data collected over the first ten weeks of a thirteen-week study: Parameter Mean SD Units Maximum plasma concentration obtained (Cmax) 54.0 13.0 ng/mL Time to attain Cmax (Tmax) 4 days Elimination half-life (T½) 30.9 13.8 days Volume of distribution (Vd) 7.3 1.5 liters Clearance (CL) 150.4 53.3 mL/day Clinical Studies Rho(D) Immune Globulin (Human) administered at 28 weeks, as well as within 72 hours of delivery, has been shown to reduce the Rh immunization rate to about 0.1-0.2%.23,24 Clinical studies demonstrated that administration of MICRhoGAM within three hours following pregnancy termination was 100% effective in preventing Rh immunization.25 Multiple studies have been performed that prove the safety and efficacy of RhoGAM in both the obstetrical and post transfusion settings. Freda, Gorman and colleagues26, 27 studied the efficacy of RhoGAM in the postpartum setting in a randomized, controlled study completed in 1967. The control group received no immunoglobulin therapy after delivery, while the test group received 300 µg of RhoGAM intramuscularly within 72 hours of delivery of an Rh-positive infant. Six months after delivery, the incidence of Rh immunization in the control group was 6.4% (32/499) versus 0.13% (1/781) in the RhoGAM group (p < 0.001). Pollack et al. performed two randomized, placebo-controlled studies in the post transfusion setting that were designed to establish the dose response relationship of RhoGAM. In the first study,15 178 (176 males, 2 females) Rh-negative volunteers received varying volumes of Rh- positive red cells; 92 subjects then received RhoGAM. A single dose of RhoGAM (1.1 mL @ 267 µg/mL) was shown to suppress anti-D formation after injection of up to 15.1 mL of Rh-positive red cells. In a companion study,4 Pollack administered 500 mL of Rh-positive whole blood to 44 Rh-negative male volunteers. Twenty-two (22) subjects received 20 µg RhoGAM per mL of Rh-positive red cells and 22 received no RhoGAM. None of the RhoGAM-treated subjects developed anti-D; 18/22 control arm subjects developed anti-D (p < 0.0001). Human clinical studies10 were subsequently performed to prove the efficacy of MICRhoGAM and the low protein (5%) formulations. In the MICRhoGAM study, 81 Rh-negative male volunteers received an initial injection of 2.5 mL Rh-positive red cells, followed by a booster injection (0.1 mL) of red cells at 26 weeks; 40 subjects received an injection of MICRhoGAM after the initial red cell injection. None of the subjects who received MICRhoGAM developed anti-D, both before and after the booster red cell injection. A similar study was performed in 1985 using the low protein formulation of RhoGAM. None of the 30 Rh-negative male volunteers who received RhoGAM after injection of 15 mL of Rh-positive red cells developed anti-D. REFERENCES 13 Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-56. 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.

CLINICAL PHARMACOLOGY Mechanism of Action RhoGAM (rho(d) immune globulin (human)) and MICRhoGAM (rho(d) immune globulin (human)) act by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells. The mechanism of a ction is unknown. RhoGAM, MICRhoGAM (rho(d) immune globulin (human)) and other Rho(D) Immune Globulin (Human) products are not effective in altering the course or consequences of Rh immunization once it has occurred. Obstetrical Use The Rh-negative obstetrical patient may be exposed to red blood cells from her Rh-positive fetus during the normal course of pregnancy or after obstetrical procedures or abdominal trauma. Clinical studies have proven that the incidence of Rh immunization as a result of pregnancy was reduced to 1-2% from 12-13% when RhoGAM (rho(d) immune globulin (human)) was given within 72 hours following delivery.10,11 Antepartum administration of Rh immune globulin at 28 weeks, as well as within 72 hours of delivery, has been shown to reduce the Rh immunization rate to about 0.1-0.2%.12,13 Clinical studies demonstrated that administration of MICRhoGAM (rho(d) immune globulin (human)) within three hours following abortion was 100% effective in preventing Rh immunization.14 Use after Rh Incompatible Transfusion An Rh-negative individual transfused with one unit of Rh-positive red blood cells has about an 80% likelihood of producing anti-D.3 However, Rh immunization can occur after exposure to < 1 mL of Rh-positive red blood cells. Protection from Rh immunization is accomplished by administering the appropriate dose of RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) , which is > 20 μg per mL of Rh-positive red blood cells, within 72 hours of transfusion of incompatible red cells.2,15 (See DOSAGE AND ADMINISTRATION section.) Pharmacokinetic Properties Pharmacokinetic studies after intramuscular injection were performed on eight Rh-negative subjects.16 Six subjects received a single dose (300 μg) of RhoGAM (rho(d) immune globulin (human)) , while two subjects received four doses (1200 μg). Plasma anti-D levels were monitored for four months using a validated method with sensitivity of approximately 1 ng/mL. The parameters measured and/or calculated included the following:

HyperRHO® S/D Mini-Dose Rho(D) Immune Globulin (Human) for Intramuscular Administration Solvent/Detergent Treated DESCRIPTION Rho(D) Immune Globulin (Human) — HyperRHO® S/D Mini-Dose treated with solvent/ detergent is a colorless to pale yellow or pink sterile solution of immune globulin containing antibodies to Rho(D) for intramuscular administration; it is preservative-free, in a latex-free delivery system. HyperRHO S/D Mini-Dose is prepared by cold ethanol fractionation from human plasma. The immune globulin is isolated from solubilized Cohn Fraction II. The Fraction II solution is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate. After the addition of solvent (TNBP) and detergent (sodium cholate), the solution is heated to 30°C and maintained at that temperature for not less than 6 hours. After the viral inactivation step, the reactants are removed by precipitation, filtration and finally ultrafiltration and diafiltration. HyperRHO S/D Mini-Dose is then incubated in the final container for 21–28 days at 20–27°C. HyperRHO S/D Mini-Dose is formulated as a 15–18% protein solution at a pH of 6.4–7.2 in 0.21–0.32 M glycine. One dose of HyperRHO S/D Mini-Dose contains not less than one-sixth the quantity of Rho(D) antibody contained in one standard dose of Rho(D) Immune Globulin (Human), and it will suppress the immunizing potential of 2.5 mL of Rho(D) positive packed red blood cells or the equivalent of whole blood (5 mL). The quantity of Rho(D) antibody in HyperRHO S/D Mini-Dose is not less than 250 IU. The removal and inactivation of spiked model enveloped and non-enveloped viruses during the manufacturing process for HyperRHO S/D Mini-Dose has been validated in laboratory studies. Human Immunodeficiency Virus, Type 1 (HIV-1), was chosen as the relevant virus for blood products; Bovine Viral Diarrhea Virus (BVDV) was chosen to model Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model Human Herpes viruses and other large enveloped DNA viruses; and Reo virus type 3 (Reo) was chosen to model non-enveloped viruses and for its resistance to physical and chemical inactivation. Significant removal of model enveloped and non-enveloped viruses is achieved at two steps in the Cohn fractionation process leading to the collection of Cohn Fraction II: the precipitation and removal of Fraction III in the processing of Fraction II + IIIW suspension to Effluent III and the filtration step in the processing of Effluent III to Filtrate III. Significant inactivation of enveloped viruses is achieved at the time of treatment of solubilized Cohn Fraction II with TNBP/sodium cholate. Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the vCJD and CJD agents.11-14 Studies of the HyperRHO S/D manufacturing process demonstrate that TSE clearance is achieved during the Pooled Plasma to Effluent III Fractionation Process (6.7 log10). These studies provide reasonable assurance that low levels of CJD/vCJD agent infectivity, if present in the starting material, would be removed. REFERENCES 11. Stenland CJ, Lee DC, Brown P, et al. Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma. Transfusion 2002. 42(11):1497-500. 12. Lee DC, Stenland CJ, Miller JL, et al. A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins. Transfusion 2001. 41(4):449-55. 13. Lee DC, Stenland CJ, Hartwell RC, et al. Monitoring plasma processing steps with a sensitive Western blot assay for the detection of the prion protein. J Virol Methods 2000. 84(1):77-89. 14. Cai K, Miller JL, Stenland CJ, et al. Solvent-dependent precipitation of prion protein. Biochim Biophys Acta 2002. 1597(1):28-35.

HyperRHO® S/D Rho(D) Immune Globulin (Human) Solvent /Detergent Treated DESCRIPTION Rho(D) Immune Globulin (Human) HyperRHO® S/D Full Dose treated with solvent/detergent is a colorless to pale yellow or pink sterile solution of immune globulin containing antibodies to Rho(D) for intramuscular administration; it is preservative-free, in a latex-free delivery system. HyperRHO S/D Full Dose is prepared by cold ethanol fractionation from human plasma. The immune globulin is isolated from solubilized Cohn fraction II. The fraction II solution is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate. After the addition of solvent (TNBP) and detergent (sodium cholate), the solution is heated to 30°C and maintained at that temperature for not less than 6 hours. After the viral inactivation step, the reactants are removed by precipitation, filtration and finally ultrafiltration and diafiltration. HyperRHO S/D Full Dose is formulated as a 15–18% protein solution at a pH of 6.4–7.2 in 0.21–0.32M glycine. HyperRHO S/D Full Dose is then incubated in the final container for 21–28 days at 20–27°C. The potency is equal to or greater than 1500 IU. Each single dose syringe contains sufficient anti-Rho(D) to effectively suppress the immunizing potential of 15 mL of Rho(D) positive red blood cells.(2-4) The removal and inactivation of spiked model enveloped and non-enveloped viruses during the manufacturing process for HyperRHO S/D Full Dose has been validated in laboratory studies. Human Immunodeficiency Virus, Type 1 (HIV-1), was chosen as the relevant virus for blood products; Bovine Viral Diarrhea Virus (BVDV) was chosen to model Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model Human Herpes viruses and other large enveloped DNA viruses; and Reo virus type 3 (Reo) was chosen to model non-enveloped viruses and for its resistance to physical and chemical inactivation. Significant removal of model enveloped and non-enveloped viruses is achieved at two steps in the Cohn fractionation process leading to the collection of Cohn Fraction II: the precipitation and removal of Fraction III in the processing of Fraction II + IIIW suspension to Effluent III and the filtration step in the processing of Effluent III to Filtrate III. Significant inactivation of enveloped viruses is achieved at the time of treatment of solubilized Cohn Fraction II with TNBP/sodium cholate. Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the vCJD and CJD agents.(18-21) Studies of the HyperRHO S/D manufacturing process demonstrate that TSE clearance is achieved during the Pooled Plasma to Effluent III Fractionation Process (6.7 log10). These studies provide reasonable assurance that low levels of CJD/vCJD agent infectivity, if present in the starting material, would be removed. REFERENCES 2. Rho(D) immune globulin (human). Med Lett Drugs Ther 16(1):3-4, 1974. 3. Pollack W, Ascari WQ, Kochesky RJ, et al: Studies on Rh prophylaxis. I. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 11(6):333-9, 1971. 4. Unpublished data on file. 18. Stenland CJ, Lee DC, Brown P, et al: Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma. Transfusion 2002. 42(11):1497-500. 19. Lee DC, Stenland CJ, Miller JL, et al: A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins. Transfusion 2001. 41(4):449-55. 20. Lee DC, Stenland CJ, Hartwell RC, et al: Monitoring plasma processing steps with a sensitive Western blot assay for the detection of the prion protein. J Virol Methods 2000. 84(1):77-89. 21. Cai K, Miller JL, Stenland CJ, et al: Solvent-dependent precipitation of prion protein. Biochim Biophys Acta 2002. 1597(1):28-35.

Find Lowest Prices on 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 DESCRIPTION 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: Virus HIV BVDV PRV PPV EMC WNV HAV Lipid Enveloped Yes Yes Yes No No Yes No Size (nm) 80-120 40-70 120-200 18-24 25-30 40-60 27-32 Genome SS-RNA SS-RNA DS-DNA SS-DNA SS-RNA SS-RNA SS-RNA 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. REFERENCES 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.

RhoGAM® Ultra-Filtered - 300 μg (1500 IU*) MICRhoGAM (rhod immune globulin human) ® Ultra-Filtered - 50 μg (250 IU*) (Rho(D) Immune Globulin (Human)) For Intramuscular Injection Only. Preservative-free, latex-free delivery system DESCRIPTION RhoGAM (rhod immune globulin human) ® and MICRhoGAM (rhod immune globulin human) ® Rho(D) Immune Globulin (Human) are sterile solutions containing 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 (rhod immune globulin human) contains sufficient anti-D (approximately 300 μg or 1500 IU)* to suppress the immune response to 15 mL (or less) of Rh-positive red blood cells.2,3 A single dose of MICRhoGAM (rhod immune globulin human) contains sufficient anti-D (approximately 50 μg or 250 IU)* to suppress the immune response to 2.5 mL (or less) of Rh-positive red blood cells. The anti-D dose is measured by comparison to the RhoGAM (rhod immune globulin human) in-house reference standard, the potency of which is established relative to the US/WHO/EP Standard Anti-D Immunoglobulin Rho(D) Immune Globulin (Human) CBER Lot 4: NIBSC Lot 01/572 (285 IU/ampoule). All donors are carefully screened by history and laboratory testing to reduce the risk of transmitting blood-borne pathogens from infected donors. Fractionation of the plasma is performed by a modification of the cold alcohol procedure that has been shown to significantly lower viral titers.4 Following fractionation, an additional viral-clearance filtration step is incorporated into the manufacturing process. This 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. The ultrafiltration step utilizes tangential flow filtration to permit filtration of IgG while effectively retarding enveloped and non-enveloped viruses above the pore-size distribution cutoff. The filter is inert to the product. Non-enveloped viruses are known to be resistant to chemical and physical inactivation.5,6 Laboratory spiking studies have shown that the cumulative viral removal capability of the RhoGAM (rhod immune globulin human) /MICRhoGAM (rhod immune globulin human) manufacturing process exceeds 13 logs for human immunodeficiency virus (HIV). Clearance of model viruses for hepatitis C virus (HCV), hepatitis B virus (HBV) and parvovirus B19 (a non-enveloped virus) exceeds 11 logs.4 The donor selection process, the fractionation process and the Viresolve ultrafiltration step are designed to 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 reported to transmit hepatitis or other infectious diseases.7 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.8 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). However, even after the fractionation and virus-filtration steps, there remains a risk of contracting blood-borne pathogens from a plasma-derived product. The final product contains approximately 5 ±1% gamma globulin, 2.9 mg/mL sodium chloride, 0.01% polysorbate 80 and 15 mg/mL glycine. Small amounts of IgA, typically less than 15 μg per dose, are present.9 The pH range is 6.20-6.55. The product contains no preservative and utilizes a latex-free delivery system. REFERENCES *The anti-D content of RhoGAM (rhod immune globulin human) /MICRhoGAM (rhod immune globulin human) is expressed as μg per dose or as International Units (IU) per dose. The conversion factor is 1 μg = 5 IU.1 †Viresolve is a trademark of Millipore Corporation. 1. Gunson HH, Bowell PJ, Kirkwood TBL. Collaborative study to recalibrate the International Reference Preparation of anti-D immunoglobulin. J Clin Pathol 1980;33:249-53. 2. Pollack W, Ascari WQ, Kochesky RJ, O'Connor RR, Ho TY, Tripodi D. Studies on Rh prophylaxis. I. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 1971;11:333-39. 3. 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. 4. Data on file at Ortho-Clinical Diagnostics, Inc. 5. Prowse C, Ludlam CA, Yap PL. Human parvovirus B19 and blood products. Vox Sang 1997;72:1-10. 6. Mannucci PM, Gdovin S, Gringeri A, Colombo M, Mele A, Schinaia N, Ciavarella N, Emerson SU, Purcell RH. Transmission of hepatitis A to patients with hemophilia by Factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. Ann Intern Med 1994;120:1-7. 7. 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. 8. 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. 9. Data on file at Ortho-Clinical Diagnostics, Inc.

INDICATIONS HyperRHO S/D Mini-Dose is recommended to prevent the isoimmunization of Rho(D) negative women at the time of spontaneous or induced abortion of up to 12 weeks' gestation provided the following criteria are met: The mother must be Rho(D) negative and must not already be sensitized to the Rho(D) antigen. The father is not known to be Rho(D) negative. Gestation is not more than 12 weeks at termination. Note: Rho(D) Immune Globulin (Human) prophylaxis is not indicated if the fetus or father can be determined to be Rh negative. If the Rh status of the fetus is unknown, the fetus must be assumed to be Rho(D) positive, and HyperRHO S/D Mini-Dose should be administered to the mother. FOR ABORTIONS OR MISCARRIAGES OCCURRING AFTER 12 WEEKS' GESTATION, A STANDARD DOSE OF Rho(D) IMMUNE GLOBULIN (HUMAN) IS INDICATED. HyperRHO S/D Mini-Dose should be administered within 3 hours or as soon as possible after  pontaneous passage or surgical removal of the products of conception. However, if HyperRHO S/D Mini-Dose is not given within this time period, consideration should still be given to its administration since clinical studies in male volunteers have demonstrated the effectiveness of Rho(D) Immune Globulin (Human) in preventing isoimmunization as long as 72 hours after infusion of Rho(D) positive red cells.9 DOSAGE AND ADMINISTRATION NEVER ADMINISTER HYPERRHO S/D MINI-DOSE INTRAVENOUSLY. INJECT ONLY INTRAMUSCULARLY. ADMINISTER ONLY TO WOMEN POST ABORTION OR POSTMISCARRIAGE OF UP TO 12 WEEKS' GESTATION. NEVER ADMINISTER TO THE NEONATE. One syringe of HyperRHO S/D Mini-Dose provides sufficient antibody to prevent Rh sensitization to 2.5 mL Rho(D) positive packed red cells or the equivalent (5 mL) of whole blood. This dose is sufficient to provide protection against maternal Rh sensitization for women undergoing spontaneous or induced abortion of up to 12 weeks' gestation. Rho(D) Immune Globulin (Human) — HyperRHO® S/D Mini-Dose should be administered within 3 hours or as soon as possible following spontaneous or induced abortion. If prompt administration is not possible, HyperRHO S/D Mini-Dose should be given within 72 hours following termination of the pregnancy. HyperRHO S/D Mini-Dose is administered intramuscularly, preferably in the deltoid muscle of the upper arm or lateral thigh muscle. The gluteal region should not be used as an injection site because of the risk of injury to the sciatic nerve.10 Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. HyperRHO S/D Mini-Dose is supplied with a syringe and an attached UltraSafe® Needle Guard for your protection and convenience. Please follow instructions below for proper use of syringe and UltraSafe® Needle Guard. Directions for Syringe Usage Remove the prefilled syringe from the package. Lift syringe by barrel, not by plunger. Twist the plunger rod clockwise until the threads are seated. With the rubber needle shield secured on the syringe tip, push the plunger rod forward a few millimeters to break any friction seal be tween the rubber stopper and the glass syringe barrel. Remove the needle shield and expel air bubbles. [Do not remove the rubber needle shield to prepare the product for administration until immediately prior to the anticipated injection time.] Proceed with hypodermic needle puncture. Aspirate prior to injection to confirm that the needle is not in a vein or artery. Inject the medication. Keeping your hands behind the needle, grasp the guard with free hand and slide forward toward needle until it is completely covered and guard clicks into place. If audible click is not heard, guard may not be completely activated. (See Diagrams A and B) Place entire prefilled glass syringe with guard activated into an approved sharps container for proper disposal. (See Diagram C) Figure A,B and C A number of factors could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use. HOW SUPPLIED HyperRHO S/D Mini-Dose package contains 10 single dose syringes. HyperRHO S/D Mini-Dose is preservativefree, in a latex-free delivery system. NDC Number Size 13533-661-06 Syringe (10 pack) Storage Store at 28°C (36 - 46°F). Do not freeze. Caution REFERENCES 9. Freda VJ, Gorman JG, Pollack W: Prevention of Rh-hemolytic disease with Rh-immune globulin. Am J Obstet Gynecol 128(4):456-60, 1977.Grifols Therapeutics Inc., Research Triangle Park, NC 27709 USA 08941120. Rev: Sep 2012 10. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP): General recommendations on immunization. MMWR 2002: 51(RR02), 1-36.

INDICATIONS Pregnancy And Other Obstetric Conditions HyperRHO S/D Full Dose is recommended for the prevention of Rh hemolytic disease of the newborn by its administration to the Rho(D) negative mother within 72 hours after birth of an Rho(D) positive infant,(12) providing the following criteria are met: The mother must be Rho(D) negative and must not already be sensitized to the Rho(D) factor. Her child must be Rho(D) positive, and should have a negative direct antiglobulin test (see PRECAUTIONS). If HyperRHO S/D Full Dose is administered antepartum, it is essential that the mother receive another dose of HyperRHO S/D Full Dose after delivery of an Rho(D) positive infant. If the father can be determined to be Rho(D) negative, HyperRHO S/D Full Dose need not be given. HyperRHO S/D Full Dose should be administered within 72 hours to all nonimmunized Rho(D) negative women who have undergone spontaneous or induced abortion, follow ing ruptured tubal pregnancy, amniocentesis or abdominal trauma unless the blood group of the fetus or the father is known to be Rho(D) negative.(7,8) If the fetal blood group cannot be determined, one must assume that it is Rho(D) positive,(2) and HyperRHO S/D Full Dose should be administered to the mother. Transfusion HyperRHO S/D Full Dose may be used to prevent isoimmunization in Rho(D) negative individuals who have been transfused with Rho(D) positive red blood cells or blood components containing red blood cells.(5,13) DOSAGE AND ADMINISTRATION NEVER ADMINISTER HYPERRHO S/D FULL DOSE INTRAVENOUSLY. INJECT ONLY INTRAMUSCULARLY. NEVER ADMINISTER TO THE NEONATE. Pregnancy And Other Obstetric Conditions For postpartum prophylaxis, administer one syringe of HyperRHO S/D Full Dose, preferably within 72 hours of delivery. Although a lesser degree of protection is afforded if Rh antibody is administered beyond the 72-hour period, HyperRHO S/D Full Dose may still be given.(7,14) Full-term deliveries can vary in their dosage requirements depending on the magnitude of the fetomaternal hemorrhage. One full dose syringe of HyperRHO S/D Full Dose provides sufficient antibody to prevent Rh sensitization if the volume of red blood cells that has entered the circulation is 15 mL or less.(2-4) In instances where a large (greater than 30 mL of whole blood or 15 mL red blood cells) fetomaternal hemorrhage is suspected, a fetal red cell count by an approved laboratory technique (e.g., modified Kleihauer-Betke acid elution stain technique) should be performed to determine the dosage of immune globulin required.(8,15) The red blood cell volume of the calculated fetomaternal hemorrhage is divided by 15 mL to obtain the number of syringes of HyperRHO S/D Full Dose for administration.(3,8,13) If more than 15 mL of red cells is suspected or if the dose calculation results in a fraction, administer the next higher whole number of syringes (e.g., if 1.4, give 2 syringes). For antenatal prophylaxis, one full dose syringe of HyperRHO S/D Full Dose is administered at approximately 28 weeks' gestation. This must be followed by another full dose, preferably within 72 hours following delivery, if the infant is Rh positive. Following threatened abortion at any stage of gestation with continuation of pregnancy, it is recommended that a full dose of HyperRHO S/D Full Dose be given. If more than 15 mL of red cells is suspected due to fetomaternal hemorrhage, the same dose modification in No. 1 above applies. Following miscarriage, abortion, or termination of ectopic pregnancy at or beyond 13 weeks' gestation, it is recommended that a HyperRHO S/D Full Dose be given. If more than 15 mL of red cells is suspected due to fetomaternal hemorrhage, the same dose modification in No. 1 above applies. If pregnancy is terminated prior to 13 weeks' gestation, where licensed, a single dose of HyperRHO® S/D Mini-Dose may be used instead of HyperRHO S/D Full Dose. Following amniocentesis at either 15 to 18 weeks' gestation or during the third trimester, or following abdominal trauma in the second or third trimester, it is recommended that a HyperRHO S/D Full Dose be administered. If there is a fetomaternal hemorrhage in excess of 15 mL of red cells, the same dose modification in No. 1 applies. If abdominal trauma, amniocentesis, or other adverse event requires the administration of HyperRHO S/D Full Dose at 13 to 18 weeks' gestation, another full dose should be given at 26 to 28 weeks. To maintain protection throughout pregnancy, the level of passively acquired anti-Rho(D) should not be allowed to fall below the level required to prevent an immune response to Rh positive red cells. The half-life of IgG is 23 to 26 days. In any case, a HyperRHO S/D Full Dose should be given within 72 hours after delivery if the baby is Rh positive. If delivery occurs within 3 weeks after the last dose, the postpartum dose may be withheld unless there is a fetomaternal hemorrhage in excess of 15 mL of red blood cells.(16) Transfusion In the case of a transfusion of Rho(D) positive red cells to an Rho(D) negative recipient, the volume of Rh positive whole blood administered is multiplied by the hematocrit of the donor unit giving the volume of red blood cells transfused. The volume of red blood cells is divided by 15 mL which provides the number of syringes of HyperRHO S/D Full Dose to be administered. If the dose calculated results in a fraction, the next higher whole number of syringes should be administered  (e.g., if 1.4, give 2 syringes). HyperRHO S/D Full Dose should be administered within 72 hours after an incompatible trans fusion, but preferably as soon as possible. Injection Procedure DO NOT INJECT INTRAVENOUSLY. DO NOT INJECT NEONATE. HyperRHO S/D Full Dose is administered intramuscularly, preferably in the deltoid muscle of the upper arm or lateral thigh muscle. The gluteal region should not be used as an injection site because of the risk of injury to the sciatic nerve.(17) A. Single Syringe Dose INJECT ENTIRE CONTENTS OF THE SYRINGE INTO THE INDIVIDUAL INTRAMUSCULARLY. B. Multiple Syringe Dose Calculate the number of syringes of HyperRHO S/D Full Dose to be given (see Dosage section). The total volume of HyperRHO S/D Full Dose can be given in divided doses at different sites at one time or the total dose may be divided and injected at intervals, provided the total dosage is given within 72 hours of the fetomaternal hemorrhage or transfusion. USING STERILE TECHNIQUE, INJECT THE ENTIRE CONTENTS OF THE CALCULATED NUMBER OF SYRINGES INTRAMUSCULARLY INTO THE PATIENT. Parenteral drug products should be inspected visually for particulate matter and discolora tion prior to administration, whenever solution and container permit. HyperRHO S/D Full Dose is supplied with a syringe and an attached UltraSafe® Needle Guard for your protection and convenience. Please follow instructions below for proper use of syringe and UltraSafe® Needle Guard. Directions for Syringe Usage Remove the prefilled syringe from the package. Lift syringe by barrel, not by plunger. Twist the plunger rod clockwise until the threads are seated. With the rubber needle shield secured on the syringe tip, push the plunger rod forward a few millimeters to break any friction seal be tween the rubber stopper and the glass syringe barrel. Remove the needle shield and expel air bubbles. [Do not remove the rubber needle shield to prepare the product for administration until immediately prior to the anticipated injection time.] Proceed with hypodermic needle puncture. Aspirate prior to injection to confirm that the needle is not in a vein or artery. Inject the medication. Keeping your hands behind the needle, grasp the guard with free hand and slide forward toward needle until it is completely covered and guard clicks into place. If audible click is not heard, guard may not be completely activated. (See Diagrams A and B) Place entire prefilled glass syringe with guard activated into an approved sharps container for proper disposal. (See Diagram C) Figure A,B and C A number of factors could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use. HOW SUPPLIED HyperRHO S/D Full Dose is available in a single dose syringe with attached needle. HyperRHO S/D Full Dose is packaged as 1 syringe per carton, and as 10 syringes per carton (10 Pack). HyperRHO S/D Full Dose is preservative-free, in a latex-free delivery system. NDC Number Size 13533-631-02 Syringe 13533-631-10 Syringe (10 Pack) Storage Store at 2–8°C (36–46°F). Do not freeze. Caution U.S. federal law prohibits dispensing without prescription. REFERENCES 1. Gunson HH, Bowell PJ, Kirkwood TBL: Collaborative study to recalibrate the International Reference Preparation of Anti-D Immunoglobulin. J Clin Pathol 33:249-53, 1980. 2. Rho(D) immune globulin (human). Med Lett Drugs Ther 16(1):3-4, 1974. 3. Pollack W, Ascari WQ, Kochesky RJ, et al: Studies on Rh prophylaxis. I. Relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion 11(6):333-9, 1971. 4. Unpublished data on file. 5. Pollack W, Ascari WQ, Crispen JF, et al: Studies on Rh prophylaxis. II. Rh immune prophylaxis after transfusion with Rh-positive blood. Transfusion 11(6):340-4, 1971. 7. The selective use of Rho(D) immune globulin (RhIG). ACOG Tech Bull 61, 1981. 8. Current uses of Rho immune globulin and detection of antibodies. ACOG Tech Bull 35, 1976. 12. Ascari WQ, Allen AE, Baker WJ, et al: Rho(D) immune globulin (human): evaluation in women at risk of Rh immunization. JAMA 205(1):1-4, 1968. 13. Prevention of Rh sensitization. WHO Tech Rep Ser 468:25, 1971. 14. Samson D, Mollison PL: Effect on primary Rh immunization of delayed administration of anti-Rh. Immunology 28:349-57, 1975. 15. Finn R, Harper DT, Stallings SA, et al: Transplacental hemorrhage. Transfusion 3(2):114-24, 1963. 16. Garraty G (ed.): Hemolytic disease of the newborn. Arlington, VA, American Association of Blood Banks, 1984, p 78. 17. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP): General recommendations on immunization. MMWR 002: 51(RR02), 1-36. Grifols Therapeutics Inc., Research Triangle Park, NC 27709 USA 3036460. Revised: Oct 2014

INDICATIONS Pregnancy and other obstetrical conditions For administration to Rh-negative women not previously sensitized to the Rho(D) factor, unless the father or baby are conclusively Rh-negative. Delivery of an Rh-positive baby irrespective of the ABO groups of the mother and baby Antepartum prophylaxis at 26 to 28 weeks gestation Antepartum fetal-maternal hemorrhage (suspected or proven) as a result of placenta previa, amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, other obstetrical manipulative procedure (e.g., version) or abdominal trauma Actual or threatened pregnancy loss at any stage of gestation Ectopic pregnancy Transfusion of Rh-incompatible blood or blood products Prevention of Rh immunization in any Rh-negative person after incompatible transfusion of Rh-positive blood or blood products (e.g., red blood cells, platelet concentrates, granulocyte concentrates) DOSAGE AND ADMINISTRATION For intramuscular use only. Do not inject RhoGAM Ultra-Filtered PLUS (rho(d) immune globulin (human)) (RhoGAM) or MICRhoGAM Ultra-Filtered PLUS (rho(d) immune globulin (human)) (MICRhoGAM) intravenously. In the case of postpartum use, the product is intended for maternal administration. Do not inject the newborn infant. Inject the entire contents of the syringe(s). For single use only. (See WARNINGS AND PRECAUTIONS) RhoGAM or MICRhoGAM should be administered within 72 hours of delivery or known or suspected exposure to Rh-positive red blood cells. There is little information concerning the effectiveness of Rho(D) Immune Globulin (Human) when given beyond this 72 hour period. In one study, Rho(D) Immune Globulin (Human) provided protection against Rh immunization in about 50% of subjects when given 13 days after exposure to Rh-positive red blood cells.1 Administer every 12 weeks starting from first injection to maintain a level of passively acquired anti-D. If delivery occurs within three weeks after the last antepartum dose, the postpartum dose may be withheld, but a test for fetal-maternal hemorrhage should be performed to determine if exposure to > 15 mL of red blood cells has occurred.2 Parenteral drug products should be inspected visually for particulate matter, discoloration and syringe damage prior to administration. Do not use if particulate matter and / or discoloration are observed. The solution should appear clear or slightly opalescent. Indications and Recommended Dosage Indication Dose Notes Pregnancy and other obstetrical conditions. Postpartum (if the newborn is Rh-positive) Administer within 72 hours of delivery. RhoGAM (300 µg) (1500 IU) Additional doses of RhoGAM are indicated when the patient has been exposed to > 15 mL of Rh- positive red blood cells. This may be determined by use of qualitative or quantitative tests for fetal-maternal hemorrhage. Antepartum: Prophylaxis at 26 to 28 weeks gestation Administer within 72 hours of suspected or proven exposure to Rh-positive red blood cells resulting from: Amniocentesis, chorionic villus sampling (CVS) and percutaneous umbilical blood sampling (PUBS) Abdominal trauma or obstetrical manipulation Ectopic pregnancy Threatened pregnancy loss after 12 weeks gestation with continuation of pregnancy Pregnancy termination (spontaneous or induced) beyond 12 weeks gestation If antepartum prophylaxis is indicated, it is essential that the mother receive a postpartum dose if the infant is Rh-positive. If RhoGAM is administered early in pregnancy (before 26 to 28 weeks), there is an obligation to maintain a level of passively acquired anti-D by administration of RhoGAM at 12-week intervals. Actual or threatened termination of pregnancy (spontaneous or induced) up to and including 12 weeks gestation Administer within 72 hours MICRhoGAM (50 µg) (250 IU) RhoGAM may be administered if MICRhoGAM is not available. Transfusion of Rh-incompatible blood or blood products Administer within 72 hours of suspected or proven exposure to Rh-positive red blood cells. • < 2.5 mL Rh-positive red blood cells MICRhoGAM (50 µg) (250 IU) RhoGAM may be administered if MICRhoGAM is not available. .5 - 15.0 mL Rh-positive red blood cells RhoGAM (300 µg) (1500 IU) > 15.0 mL Rh-positive red blood cells RhoGAM (300 µg) (1500 IU) (multiple syringes) Additional doses of RhoGAM are indicated when the patient has been exposed to > 15 mL of Rh- positive red blood cells. Administer 20 µg of RhoGAM per mL of Rh-positive red blood cell exposure. Multiple doses may be administered at the same time or at spaced intervals, as long as the total dose is administered within three days of exposure. RhoGAM Administration Each single dose prefilled syringe of RhoGAM contains 300 µg (1500 IU) of Rho(D) Immune Globulin (Human). This is the dose for the indications associated with pregnancy at or beyond 13 weeks unless there is clinical or laboratory evidence of a fetal-maternal hemorrhage (FMH) in excess of 15 mL of Rh-positive red blood cells. MICRhoGAM Administration Each single dose prefilled syringe of MICRhoGAM contains 50 µg (250 IU) of Rho(D) Immune Globulin (Human). This dose will suppress the immune response to up to 2.5 mL of Rh-positive red blood cells. MICRhoGAM is indicated within 72 hours after termination of pregnancy up to and including 12 weeks gestation. At or beyond 13 weeks gestation, RhoGAM should be administered instead of MICRhoGAM. Multiple Dosage Multiple doses of RhoGAM are required if a FMH exceeds 15 mL, an event that is possible but unlikely prior to the third trimester of pregnancy and is most likely at delivery. Patients known or suspected to be at increased risk of FMH should be tested for FMH by qualitative or quantitative methods.3 In efficacy studies, RhoGAM was shown to suppress Rh immunization in all subjects when given at a dose of > 20 µg per mL of Rh- positive red blood cells.4 Thus, a single dose of RhoGAM will suppress the immune response after exposure to < 15 mL of Rh-positive red blood cells. However, in clinical practice, laboratory methods used to determine the amount of exposure (volume of transfusion or FMH) to Rh-positive red blood cells are imprecise.5,6 Therefore, administration of more than 20 µg of RhoGAM per mL of Rh-positive red blood cells should be considered whenever a large FMH or red blood cell exposure is suspected or documented.6 Multiple doses may be administered at the same time or at spaced intervals, as long as the total dose is administered within three days of exposure.7 Dosage Frequency To maintain an adequate level of anti-D, RhoGAM should be administered every 12 weeks. The exact timing for the injection is based on 12 week intervals starting from the administration of the first injection. If delivery of the baby does not occur 12 weeks after the administration of the standard antepartum dose (at 26 to 28 weeks), a second dose is recommended to maximize protection antepartum. If delivery occurs within three weeks after the last antepartum dose, the postpartum dose may be withheld, but a test for FMH should be performed to determine if exposure to > 15 mL of red blood cells has occurred.2 Administration Administer injection per standard protocol. Note: When administering an intramuscular injection, place fingers in contact with syringe barrel through windows in shield to prevent possible premature activation of safety guard. Slide safety guard over needle. After injection, use free hand to slide safety guard over needle. An audible "click" indicates proper activation. Keep hands behind needle at all times. Dispose of the syringe in accordance with local regulations. HOW SUPPLIED Dosage Forms and Strength RhoGAM® Ultra-Filtered PLUS (rho(d) immune globulin (human)) - 300 µg (1500 IU)* - Prefilled Syringes MICRhoGAM® Ultra-Filtered PLUS (rho(d) immune globulin (human)) - 50 µg (250 IU)* - Prefilled Syringes *The anti-D content of RhoGAM / MICRhoGAM is expressed as µg per dose or as International Units (IU) per dose. The conversion factor is 1 µg = 5 IU.8 Storage and Handling RhoGAM Ultra-Filtered PLUS (rho(d) immune globulin (human)) package sizes: 1 prefilled single-dose syringe of RhoGAM (Product Code 780501) NDC 0562-7805-01 1 package insert, 1 control form, 1 patient identification card 5 prefilled single-dose syringes of RhoGAM (Product Code 780505) NDC 0562-7805-05 5 package inserts, 5 control forms, 5 patient identification cards 25 prefilled single-dose syringes of RhoGAM (Product Code 780525) NDC 0562-7805-25 25 package inserts, 25 control forms, 25 patient identification cards MICRhoGAM Ultra-Filtered PLUS (rho(d) immune globulin (human)) package sizes: 1 prefilled single-dose syringe of MICRhoGAM (Product Code 780601) NDC 0562-7806-01 1 package insert, 1 control form, 1 patient identification card 5 prefilled single-dose syringes of MICRhoGAM (Product Code 780605) NDC 0562-7806-05 5 package inserts, 5 control forms, 5 patient identification cards 25 prefilled single-dose syringes of MICRhoGAM (Product Code 780625) NDC 0562-7806-25 25 package inserts, 25 control forms, 25 patient identification cards Store at 2 to 8°C. Do not store frozen. Do not use after the expiration date printed the syringe. REFERENCES 1 Samson D, Mollison PL. Effect on primary Rh immunization of delayed administration of anti-Rh. Immunol 1975;28:349-57. 2 Garratty G, ed. Hemolytic disease of the newborn. Arlington, VA: American Association of Blood Banks, 1984:78. 3 Urbaniak SJ. Statement from the Consensus Conference on Anti-D Prophylaxis, The Royal College of Physicians of Edinburgh & The Royal College of Obstetricians and Gynaecologists, UK. Vox Sang 1998;74:127-28. 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. 5 Bayliss KM, Kueck DB, Johnson ST, Fueger JT, McFadden PW, Mikulski D, Gottschall JL. Detecting fetomaternal hemorrhage: a comparison of five methods. Transfusion 1991;31:303-7. 6 Kumpel BM. Quantification of anti-D and fetomaternal hemorrhage by flow cytometry (editorial). Transfusion 2000;40:6-9. 7 AABB Technical Manual. 15th ed. Bethesda, Maryland: AABB, 2005. 8 Gunson HH, Bowell PJ, Kirkwood TBL. Collaborative study to recalibrate the International Reference Preparation of anti-D immunoglobulin. J Clin Pathol 1980;33:249-53. Ortho-Clinical Diagnostics,Inc. A Johnson & Johnson company, Raritan, New Jersey 08869. Issued March 2007. FDA rev date: n/a

INDICATIONS Pregnancy and Other Obstetrical Conditions in Rh-Negative Women, Unless the Father or Baby are Conclusively Rh Negative Pregnancy/delivery of an Rh-positive baby irrespective of the ABO groups of the mother and baby Abortion/threatened abortion at any stage of gestation Ectopic pregnancy Antepartum fetal-maternal hemorrhage (suspected or proven) resulting from antepartum hemorrhage (e.g., placenta previa), amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, other obstetrical manipulative procedure (e.g., version) or abdominal trauma Transfusion of Rh incompatible blood or blood products Transfusion Prevention of Rh immunization in any Rh-negative person after incompatible transfusion of Rh-positive blood or blood products (e.g., red blood cells, platelet concentrates, granulocyte concentrates) DOSAGE AND ADMINISTRATION For intramuscular use only. Do not inject RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) intravenously. In the case of postpartum use, the product is intended for maternal administration. Do not inject the newborn infant. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. A single dose (approximately 50 μg)* is contained in each prefilled syringe of MICRhoGAM (rho(d) immune globulin (human)) . This dose will suppress the immune response to 2.5 mL of Rh-positive red blood cells. MICRhoGAM (rho(d) immune globulin (human)) is therefore indicated within 72 hours after termination of pregnancy up to and including 12 weeks' gestation. At or beyond 13 weeks' gestation, RhoGAM (rho(d) immune globulin (human)) should be administered instead of MICRhoGAM (rho(d) immune globulin (human)) . A single dose (approximately 300 μg)* is contained in each prefilled syringe of RhoGAM (rho(d) immune globulin (human)) . This is the usual dose for the indications associated with pregnancy unless there is clinical or laboratory evidence of a fetal-maternal hemorrhage (FMH) in excess of 15 mL of Rh-positive red blood cells. RhoGAM (rho(d) immune globulin (human)) should be administered within 72 hours of known or suspected exposure to Rh-positive red blood cells. The indications and recommended dosage for RhoGAM (rho(d) immune globulin (human)) and MICRhoGAM (rho(d) immune globulin (human)) are summarized in the following table. Indications and Recommended Dosage Indication Indicated Dosea (approximately) Postpartum (if the newborn is Rh-positive) 300 μgb Antepartum: Prophylaxis at 26 to 28 weeks' gestationc 300 μg Antepartum: Amniocentesis, chorionic villus sampling 300 μg (CVS) and percutaneous umbilical blood sampling (PUBS) Antepartum: Abdominal trauma or obstetrical manipulation 300 μg Antepartum: Ectopic pregnancyd 300 μg Antepartum: Abortion or threatened abortion at any stage of gestation with continuation of pregnancyd 300 μg Transfusion of Rh-incompatible blood or blood productsd 300 μg a Additional doses of RhoGAM (rho(d) immune globulin (human)) are indicated when the patient has been exposed to > 15 mL of Rh-positive red blood cells. This may be determined by use of qualitative or quantitative tests for FMH (see below). b See DESCRIPTION section. c If antepartum prophylaxis is indicated, it is essential that the mother receive a postpartum dose if the infant is Rh-positive. d If abortion or termination of pregnancy occurs up to and including 12 weeks' gestation, or less than 2.5 mL of Rh-incompatible red blood cells were administered, a single dose of MICRhoGAM (rho(d) immune globulin (human)) Rho(D) Immune Globulin (Human) (approximately 50 μg)* may be used instead of RhoGAM (rho(d) immune globulin (human)) . If RhoGAM (rho(d) immune globulin (human)) is administered for one of the above indications early in pregnancy (before 26 to 28 weeks), there is an obligation to maintain a level of passively acquired anti-D by administration of RhoGAM (rho(d) immune globulin (human)) at 12-week intervals. RhoGAM (rho(d) immune globulin (human)) should be administered within 72 hours of delivery or exposure to Rh-positive red blood cells. There is little information concerning the effectiveness of Rh Immune Globulin when given beyond this 72-hour period. In one study, Rh Immune Globulin provided protection against Rh immunization in about 50% of subjects when given 13 days after exposure to Rh-positive cells.21 If delivery occurs within three weeks after the last antepartum dose, the postpartum dose may be withheld, but a test for FMH should be performed to determine if exposure to >15 mL of red cells has occurred.22 Multiple doses of RhoGAM (rho(d) immune globulin (human)) are required if an FMH exceeds 15 mL. Patients in whom FMH is suspected should be tested for FMH by qualitative or quantitative methods.23 In efficacy studies, RhoGAM (rho(d) immune globulin (human)) was shown to suppress Rh immunization in all subjects when given at a dose of >20 μg per mL of Rh-positive red blood cells.3 Thus, a single dose of RhoGAM (rho(d) immune globulin (human)) will suppress the immune response after exposure to <15 mL of Rh-positive red blood cells. However, in clinical practice, laboratory methods used to determine the amount of exposure (volume of transfusion or FMH) to Rh-positive red blood cells are imprecise.24,25 Therefore, administration of more than 20 μg of RhoGAM (rho(d) immune globulin (human)) per mL of Rh-positive red blood cells should be considered whenever a large FMH or red blood cell exposure is suspected or documented.25 When multiple doses are required, consult your pharmacy for pooling directions. Multiple doses may be administered at the same time or at spaced intervals, as long as the total dose is administered within three days of exposure. Administer injection. Administer injection per standard protocol. Note: When administering an intramuscular injection, place fingers in contact with syringe barrel through windows in shield to prevent possible premature activation of safety guard. Slide safety guard over needle. After injection, use free hand to slide safety guard over needle. An audible “click” indicates proper activation. Keep hands behind needle at all times. HOW SUPPLIED RhoGAM (rho(d) immune globulin (human)) is available in packages containing: 1 prefilled single-dose syringe of RhoGAM (rho(d) immune globulin (human)) (Product Code 780701) NDC 0562-7807-01 1 package insert 1 control form 1 patient identification card and 5 prefilled single-dose syringes of RhoGAM (rho(d) immune globulin (human)) (Product Code 780710) NDC 0562-7807-06 5 package inserts 5 control forms 5 patient identification cards and 25 prefilled single-dose syringes of RhoGAM (rho(d) immune globulin (human)) (Product Code 780715) NDC 0562-7807-26 25 package inserts 25 control forms 25 patient identification cards MICRhoGAM (rho(d) immune globulin (human)) is available in packages containing: 1 prefilled single-dose syringe of MICRhoGAM (rho(d) immune globulin (human)) (Product Code 780801) NDC 0562-7808-01 1 package insert 1 control form 1 patient identification card and 5 prefilled single-dose syringes of MICRhoGAM (rho(d) immune globulin (human)) (Product Code 780810) NDC 0562-7808-06 5 package inserts 5 control forms 5 patient identification cards and 25 prefilled single-dose syringes of MICRhoGAM (rho(d) immune globulin (human)) (Product Code 780815) NDC 0562-7808-26 25 package inserts 25 control forms 25 patient identification cards Storage Store at 2 to 8°C. Do not store frozen. REFERENCES 3. 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. 20. Data on file at Ortho-Clinical Diagnostics, Inc. 21. Samson D, Mollison PL. Effect on primary Rh immunization of delayed administration of anti-Rh. Immunol 1975;28:349-57. 22. Garratty G, ed. Hemolytic disease of the newborn. Arlington, VA: American Association of Blood Banks, 1984:78. 23. Urbaniak SJ. Statement from the Consensus Conference on Anti-D Prophylaxis, The Royal College of Physicians of Edinburgh & The Royal College of Obstetricians and Gynaecologists, UK. Vox Sang 1998;74:127-28. 24. Bayliss KM, Kueck DB, Johnson ST, Fueger JT, McFadden PW, Mikulski D, Gottschall JL. Detecting fetomaternal hemorrhage: a comparison of five methods. Transfusion 1991;31:303-7. 25. Kumpel BM. Quantification of anti-D and fetomaternal hemorrhage by flow cytometry (editorial). Transfusion 2000;40:6-9. Ortho-Clinical Diagnostics, Inc, Raritan, New Jersey 08869, Revised October 2005. FDA revision date: n/a

PATIENT INFORMATION The Rh Factor and Your Pregnancy Information About Pregnancy Protection The Rh Factor and When It Is Important The Rh factor is one of many blood group antigens found on the surface of red blood cells. If you have this antigen you are considered Rh positive. If you don't, then you are considered Rh negative. Everyone is either Rh positive or Rh negative. One type is neither better nor worse than the other, only different. Your Rh factor is important if you are an Rh negative woman and you become pregnant, or if you receive a blood trans fusion. How the Rh Factor Can Affect Your Future If you have Rh negative blood, there are two situations that can affect you: 1. If the father of your baby is Rh positive, the baby will probably be Rh positive too. An Rh negative woman carrying an Rh positive baby may have an immune reaction if some of the baby's Rh positive blood cells enter her bloodstream. This immune reaction, called isoimmunization, means your body's defense system recognizes Rh positive blood as foreign from your own and produces “antibodies” to destroy the invading Rh positive blood cells. The passage of blood from the baby to the mother's bloodstream happens most often at delivery, but can also occur during miscarriage, the termination of pregnancy, amnio centesis (test performed to determine fetal health), or due to an injury or trauma. It is important to note that a small number of women develop antibodies to Rh positive blood cells during pregnancy for no apparent reason. Antibodies to Rh positive blood may not be a problem in first pregnancies; however, the antibodies stay in your blood stream, ready to attack invading Rh positive blood cells, for many years to come. This can lead to problems in future pregnancies by causing miscarriage or a disease known as hemolytic disease of the newborn. Babies born to Rh positive mothers, regardless of the father's blood type, will usually be free of the dangers of hemolytic disease. 2. Someday it may become necessary for you to receive a blood transfusion. If Rh positive antibodies already reside in your bloodstream due to isoimmunization and the blood you receive is Rh positive due to error or lifesaving reasons, your Rh positive antibodies will become mobilized and de stroy the donor Rh positive cells. As a result, the transfusion could be unsuccessful and possibly harmful to you. Hemolytic Disease of the Newborn: A Threat to Your Baby When an Rh negative woman has Rh positive antibodies in her blood and the baby she is carrying is Rh positive, the antibod ies could possibly enter the baby's bloodstream, attack the baby's red blood cells and cause hemolytic disease of the new born. At birth, the infant suffering from hemolytic disease may be jaundiced and anemic or suffer permanent damage of the brain and central nervous system which may result in mental retardation, hearing loss, or cerebral palsy. Extensive medi cal care can be required, including an exchange transfusion, in which all of the baby's blood is replaced. This usually stops the destruction of the baby's red blood cells and gives the infant a chance to survive. The risk of hemolytic disease of the newborn is slight with the first baby, but increases with each successive pregnancy. Preventing Hemolytic Disease HyperRHO® S/D, Rho(D) Immune Globulin (Human) can pre vent hemolytic disease of the newborn, provided Rh positive antibodies do not already reside in your bloodstream. HyperRHO S/D is a specially prepared gamma globulin with a high level of preformed antibodies against Rh positive blood cells. The injection of HyperRHO S/D destroys any Rh positive blood cells that may have entered the mother's bloodstream and prevents the mother's immune system from producing Rh positive antibodies; thus protecting the baby from developing hemolytic disease. HyperRHO S/D Full Dose — When Prescribed Pregnancy and Other Obstetric Conditions Pertaining to Rh Negative Women HyperRHO S/D Full Dose is administered during pregnancy if you fall into a high-risk category. For example, you are at risk of producing Rh positive antibodies if you have an amniocentesis procedure performed, or if you have a miscarriage or other termination of pregnancy at or beyond 13 weeks' gestation. Laboratory findings have shown that some Rh negative women develop Rh positive antibodies during the last weeks of pregnancy even without an antibody-stimulating event. As a preventive measure, your physician will probably recommend the first injection of HyperRHO S/D Full Dose at the 28th week of pregnancy. In both of the above situations, if the blood type of the father or baby can be determined to be Rh negative, an injection of HyperRHO S/D is not required. Another injection of HyperRHO S/D Full Dose is administered within 72 hours of delivery of an Rh positive baby. Blood Transfusion HyperRHO S/D Full Dose may be used to prevent isoimmunization in Rh negative individuals who have been transfused with Rh positive red blood cells or blood components containing red blood cells. HyperRHO S/D Mini-Dose — When Prescribed A single dose of HyperRHO S/D Mini-Dose may be prescribed for an Rh negative woman instead of HyperRHO S/D Full Dose in the event of miscarriage or other termination of pregnancy occurring prior to 13 weeks' gestation. HyperRHO S/D Mini-Dose is not required if the blood type of the father or fetus can be determined to be Rh negative. Will You Need HyperRHO S/D Again? HyperRHO S/D provides protection only if you have not already produced Rh positive antibodies. Women who have developed antibodies through previous pregnancy, miscarriage, other ter mination of pregnancy, or blood transfusion cannot be protected by HyperRHO S/D. This is why with each pregnancy it is important to have HyperRHO S/D injections within the prescribed time period. Reactions to HyperRHO S/D You may feel a temporary soreness at the site of the injection. You may also have a slight and temporary change in body tem perature. In very rare instances, an allergic type of reaction can occur, for which your physician will take appropriate measures. Delivering a Sound, Healthy Baby Your physician can answer any questions you may have about receiving a HyperRHO S/D injection to prevent hemolytic disease of the newborn. If you know that you are Rh negative and you are pregnant, you should discuss your situation with your phy sician. Today, with HyperRHO S/D, hemolytic disease of the newborn can be reduced to its lowest possible rate of incidence. Grifols Therapeutics Inc., Research Triangle Park, NC 27709 USA 08941120, U.S. License No. 1871 (Rev. September 2012) Development of Hemolytic Disease 1. Rh positive (+) father. Rh negative (-) mother. 2. Pregnancy: Rh– mother is carrying Rh+ baby. 3. The passage of Rh+ blood from the baby to the mother's bloodstream happens most often at delivery, but can also occur during miscarriage, other termination of pregnancy, amniocentesis, or due to injury or trauma. 4. Rh+ antibodies stay in your blood stream, ready to attack invading Rh+ blood cells, for many years to come. 5. Next pregnancy, mother's Rh+ anti bodies enter baby's Rh+ bloodstream, attacking baby's blood cells and caus ing hemolytic disease of the newborn.

PATIENT INFORMATION The Rh Factor and Your Pregnancy Information About Pregnancy Protection The Rh Factor and When It Is Important The Rh factor is one of many blood group antigens found on the surface of red blood cells. If you have this antigen you are considered Rh positive. If you don't, then you are considered Rh negative. Everyone is either Rh positive or Rh negative. One type is neither better nor worse than the other, only different. Your Rh factor is important if you are an Rh negative woman and you become pregnant, or if you receive a blood trans fusion. How the Rh Factor Can Affect Your Future If you have Rh negative blood, there are two situations that can affect you: 1. If the father of your baby is Rh positive, the baby will probably be Rh positive too. An Rh negative woman carrying an Rh positive baby may have an immune reaction if some of the baby's Rh positive blood cells enter her bloodstream. This immune reaction, called isoimmunization, means your body's defense system recognizes Rh positive blood as foreign from your own and produces “antibodies” to destroy the invading Rh positive blood cells. The passage of blood from the baby to the mother's bloodstream happens most often at delivery, but can also occur during miscarriage, the termination of pregnancy, amnio centesis (test performed to determine fetal health), or due to an injury or trauma. It is important to note that a small number of women develop antibodies to Rh positive blood cells during pregnancy for no apparent reason. Antibodies to Rh positive blood may not be a problem in first pregnancies; however, the antibodies stay in your blood stream, ready to attack invading Rh positive blood cells, for many years to come. This can lead to problems in future pregnancies by causing miscarriage or a disease known as hemolytic disease of the newborn. Babies born to Rh positive mothers, regardless of the father's blood type, will usually be free of the dangers of hemolytic disease. 2. Someday it may become necessary for you to receive a blood transfusion. If Rh positive antibodies already reside in your bloodstream due to isoimmun ization and the blood you receive is Rh positive due to error or lifesaving reasons, your Rh positive antibodies will become mobilized and de stroy the donor Rh positive cells. As a result, the transfusion could be unsuccessful and possibly harmful to you. Hemolytic Disease of the Newborn: A Threat to Your Baby When an Rh negative woman has Rh positive antibodies in her blood and the baby she is carrying is Rh positive, the antibod ies could possibly enter the baby's bloodstream, attack the baby's red blood cells and cause hemolytic disease of the new born. At birth, the infant suffering from hemolytic disease may be jaundiced and anemic or suffer permanent damage of the brain and central nervous system which may result in mental retardation, hearing loss, or cerebral palsy. Extensive medi cal care can be required, including an exchange transfusion, in which all of the baby's blood is replaced. This usually stops the destruction of the baby's red blood cells and gives the infant a chance to survive. The risk of hemolytic disease of the newborn is slight with the first baby, but increases with each successive pregnancy. Preventing Hemolytic Disease HyperRHO® S/D, Rho(D) Immune Globulin (Human) can pre vent hemolytic disease of the newborn, provided Rh positive antibodies do not already reside in your bloodstream. HyperRHO S/D is a specially prepared gamma globulin with a high level of preformed antibodies against Rh positive blood cells. The injection of HyperRHO S/D destroys any Rh positive blood cells that may have entered the mother's bloodstream and prevents the mother's immune system from producing Rh positive antibodies; thus protecting the baby from developing hemolytic disease. HyperRHO S/D Full Dose — When Prescribed Pregnancy and Other Obstetric Conditions Pertaining to Rh Negative Women HyperRHO S/D Full Dose is administered during pregnancy if you fall into a high-risk category. For example, you are at risk of producing Rh positive antibodies if you have an amniocentesis procedure performed, or if you have a miscarriage or other termination of pregnancy at or beyond 13 weeks' gestation. Laboratory findings have shown that some Rh negative women develop Rh positive antibodies during the last weeks of pregnancy even without an antibody-stimulating event. As a preventive measure, your physician will probably recommend the first injection of HyperRHO S/D Full Dose at the 28th week of pregnancy. In both of the above situations, if the blood type of the father or baby can be determined to be Rh negative, an injection of HyperRHO S/D is not required. Another injection of HyperRHO S/D Full Dose is administered within 72 hours of delivery of an Rh positive baby. Blood Transfusion HyperRHO S/D Full Dose may be used to prevent isoimmunization in Rh negative individuals who have been transfused with Rh positive red blood cells or blood components containing red blood cells. HyperRHO S/D Mini-Dose — When Prescribed A single dose of HyperRHO S/D Mini-Dose may be prescribed for an Rh negative woman instead of HyperRHO S/D Full Dose in the event of miscarriage or other termination of pregnancy occurring prior to 13 weeks' gestation. HyperRHO S/D Mini-Dose is not required if the blood type of the father or fetus can be determined to be Rh negative. Will You Need HyperRHO S/D Again? HyperRHO S/D provides protection only if you have not already produced Rh positive antibodies. Women who have developed antibodies through previous pregnancy, miscarriage, other ter mination of pregnancy, or blood transfusion cannot be protected by HyperRHO S/D. This is why with each pregnancy it is important to have HyperRHO S/D injections within the prescribed time period. Reactions to HyperRHO S/D You may feel a temporary soreness at the site of the injection. You may also have a slight and temporary change in body tem perature. In very rare instances, an allergic type of reaction can occur, for which your physician will take appropriate measures. Delivering a Sound, Healthy Baby Your physician can answer any questions you may have about receiving a HyperRHO S/D injection to prevent hemolytic disease of the newborn. If you know that you are Rh negative and you are pregnant, you should discuss your situation with your phy sician. Today, with HyperRHO S/D, hemolytic disease of the newborn can be reduced to its lowest possible rate of incidence. Development of Hemolytic Disease 1. Rh positive (+) father. Rh negative (–) mother. 2. Pregnancy: Rh– mother is carrying Rh+ baby. 3. The passage of Rh+ blood from the baby to the mother's bloodstream happens most often at delivery, but can also occur during miscarriage, other termination of pregnancy, amniocentesis, or due to injury or trauma. 4. Rh+ antibodies stay in your blood stream, ready to attack invading Rh+ blood cells, for many years to come. 5. Next pregnancy, mother's Rh+ anti bodies enter baby's Rh+ bloodstream, attacking baby's blood cells and caus ing hemolytic disease of the newborn. How HyperRHO S/D Immune Globulin Can Prevent Hemolytic Disease 1. You will probably be given two injections of HyperRHO S/D Full Dose, one at the 28th week of your pregnancy and another within 72 hours of delivery, miscarriage or other termination of pregnancy. A single injection of HyperRHO S/D Mini-Dose may be prescribed instead of HyperRHO S/D Full Dose in the event of miscarriage or other termination of pregnancy occurring prior to 13 weeks' gestation. 2. HyperRHO S/D immunization prevents formation of mother's own Rh+ antibodies. Mother's bloodstream remains free of Rh+ antibodies. 3. Next pregnancy, baby develops normally. HyperRHO S/D should be administered following delivery, miscarriage, or other termination of pregnancy to continue protection if baby is Rh+.

PATIENT INFORMATION As with all immune globulin preparations, the physician should discuss the risks and benefits with the patient. The most common adverse reactions are local reactions including swelling, induration, redness and mild pain at the site of injection, and a small number of patients have noted a slight elevation in temperature. Systemic reactions to RhoGAM or MICRhoGAM are extremely rare, however allergic responses to RhoGAM or MICRhoGAM may occur. Patients should be observed for at least 20 minutes after administration. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. The physician should provide the patient with a completed RhoGAM Patient Identification Card and advise the patient to retain the card and present it to other health care providers when appropriate.

PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

OVERDOSE No information provided. CONTRAINDICATIONS None known.

OVERDOSE Repeated administration or increased dosage in Rh-negative individuals should not cause more severe or more frequent adverse reactions than the normal dose. Patients who receive RhoGAM or MICRhoGAM for Rh-incompatible transfusion should be monitored by clinical and laboratory means due to the risk of a hemolytic reaction. CONTRAINDICATIONS The use of RhoGAM and MICRhoGAM is contraindicated in Rh-positive individuals.

OVERDOSE Patients who receive RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) for Rh-incompatible transfusion should be monitored by clinical and laboratory means due to the risk of a hemolytic reaction. CONTRAINDICATIONS Individuals known to have had an anaphylactic or severe systemic reaction to human globulin should not receive RhoGAM (rho(d) immune globulin (human)) , MICRhoGAM (rho(d) immune globulin (human)) or any other Rho(D) Immune Globulin (Human).

SIDE EFFECTS Reactions to HyperRHO S/D Mini-Dose are infrequent in Rho(D) negative individuals and consist primarily of slight soreness at the site of injection and slight temperature elevation. While sensitization to repeated injections of human globulin is extremely rare, it has occurred. DRUG INTERACTIONS Other antibodies in the HyperRHO S/D Mini-Dose preparation may interfere with the response to live vaccines such as measles, mumps, polio or rubella. Therefore, immunization with live vaccines should not be given within 3 months after HyperRHO S/D Mini-Dose administration.

SIDE EFFECTS Reactions to Rho(D) Immune Globulin (Human) are infrequent in Rho(D) negative individuals and consist primarily of slight soreness at the site of injection and slight temperature elevation. While sensitization to repeated injections of human immune globulin is extremely rare, it has occurred. Elevated bilirubin levels have been reported in some individuals receiving multiple doses of Rho(D) Immune Globulin (Human) following mismatched transfusions. This is believed to be due to a relatively rapid rate of foreign red cell destruction. DRUG INTERACTIONS Other antibodies in the Rho(D) Immune Globulin (Human) preparation may interfere with the response to live vaccines such as measles, mumps, polio or rubella. Therefore, immunization with live vaccines should not be given within 3 months after Rho(D) Immune Globulin (Human) administration. Drug/Laboratory Interactions Babies born of women given Rho(D) Immune Globulin (Human) ante partum may have a weakly positive direct antiglobulin test at birth. Passively acquired anti-Rho(D) may be detected in maternal serum if antibody screening tests are performed subsequent to antepartum or postpartum administration of Rho(D) Immune Globulin (Human).

SIDE EFFECTS Adverse events (AE) after administration of RhoGAM and MICRhoGAM are rare. The most frequently reported AEs are anti-D formation and injection site reactions, such as swelling, induration, redness and mild pain or warmth. Possible systemic reactions are skin rash, body aches or a slight elevation in temperature. Severe systemic allergic reactions are extremely rare. Patients should be observed for at least 20 minutes after administration. There have been no reported fatalities due to anaphylaxis or any other cause related to RhoGAM or MICRhoGAM administration. As with any Rho(D) Immune Globulin (Human), administration to patients who are Rh-positive or have received Rh-positive red blood cells may result in signs and symptoms of a hemolytic reaction, including fever, back pain, nausea and vomiting, hypo- or hypertension, hemoglobinuria/emia, elevated bilirubin and creatinine and decreased haptoglobin. RhoGAM and MICRhoGAM contain a small quantity of IgA (less than 15 µg per dose).10 Although high doses of intravenous immune globulin containing IgA at levels of 270- 720 µg/mL have been given without incident during treatment of patients with high-titered antibodies to IgA,11 the attending physician must weigh the benefit against the potential risks of hypersensitivity reactions. DRUG INTERACTIONS Immune globulin preparations including Rho(D) Immune Globulin (Human) may impair the efficacy of live vaccines such as measles, mumps and varicella. Administration of live vaccines should generally be delayed until 12 weeks after the final dose of immune globulin. If an immune globulin is administered within 14 days after administration of a live vaccine, the immune response to the vaccination may be inhibited.12 Because of the importance of rubella immunity among women of childbearing age, the postpartum vaccination of rubella-susceptible women with rubella or MMR vaccine should not be delayed because of the receipt of Rho(D) Immune Globulin (Human) during the last trimester of pregnancy or at delivery. Vaccination should occur immediately after delivery and if possible, testing should be performed after 3 or more months to ensure immunity to rubella and if necessary, to measles.12 REFERENCES 10 Data on file at Ortho-Clinical Diagnostics, Inc. 11 Cunningham-Rundles C, Zhuo Z, Mankarious S, Courter S. Long-term use of IgA- depleted intravenous immunoglobulin in immunodeficient subjects with anti-IgA antibodies. J Clin Immunol 1993;13:272-78. 12 Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. MMWR 2002;51 (No. RR-2):6-7.

SIDE EFFECTS Adverse events (AE) after administration of RhoGAM (rho(d) immune globulin (human)) Ultra-Filtered and MICRhoGAM (rho(d) immune globulin (human)) Ultra-Filtered are reported infrequently. The most frequently reported AEs are anti-D formation and skin reactions, such as swelling, induration, redness and mild pain at the site of injection. Systemic allergic reactions to RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) are extremely rare. There have been no reported fatalities due to anaphylaxis or any other cause related to RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) administration. As with any Rho(D) Immune Globulin (Human), administration to patients who have received Rh-positive red blood cells may result in signs and symptoms of a hemolytic reaction, including fever, back pain, nausea and vomiting, hypo- or hypertension, hemoglobinuria/emia, elevated bilirubin and creatinine and decreased haptoglobin. DRUG INTERACTIONS No information provided.

WARNINGS HyperRHO S/D Mini-Dose is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob Disease (CJD) agent that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Therapeutics Inc. [1-800-520-2807]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient. NEVER ADMINISTER HYPERRHO S/D MINI-DOSE INTRAVENOUSLY. INJECT ONLY INTRAMUSCULARLY. ADMINISTER ONLY TO WOMEN POSTABORTION OR POSTMISCARRIAGE OF UP TO 12 WEEKS' GESTATION. NEVER ADMINISTER TO THE NEONATE. HyperRHO S/D Mini-Dose should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immune globulin preparations. The attending physician who wishes to administer HyperRHO S/D Mini-Dose to persons with isolated immunoglobulin A (IgA) deficiency must weigh the benefits of immunization against the potential risks of hypersensitivity reactions. Such persons have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products that contain IgA. As with all preparations administered by the intramuscular route, bleeding complications may be encountered in patients with thrombocytopenia or other bleeding disorders. PRECAUTIONS General Although systemic reactions to immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactic symptoms. Pregnancy Category C Animal reproduction studies have not been conducted with HyperRHO S/D Mini-Dose. It is also not known whether HyperRHO S/D Mini-Dose can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It should be again noted, however, that HyperRHO S/D Mini-Dose is not indicated for use during pregnancy and it should be administered only postabortion or postmiscarriage. Pediatric Use Safety and effectiveness in the pediatric population have not been established.

WARNINGS HyperRHO S/D Full Dose is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob Disease (CJD) agent that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Therapeutics Inc. [1-800-520-2807]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient. NEVER ADMINISTER HYPERRHOS/D FULL DOSE INTRAVENOUSLY. INJECT ONLY INTRAMUSCULARLY. NEVER ADMINISTER TO THE NEONATE. Rho(D) Immune Globulin (Human) should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immunoglobulin preparations. The attending physician who wishes to administer Rho(D) Immune Globulin (Human) to persons with isolated immunoglobulin A (IgA) deficiency must weigh the benefits of immuni zation against the potential risks of hypersensitivity reactions. Such persons have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products that contain IgA. As with all preparations administered by the intramuscular route, bleeding complications may be encountered in patients with thrombocytopenia or other bleeding disorders. PRECAUTIONS General A large fetomaternal hemorrhage late in pregnancy or following delivery may cause a weak mixed field positive Du test result. If there is any doubt about the mother's Rh type, she should be given Rho(D) Immune Globulin (Human). A screening test to detect fetal red blood cells may be helpful in such cases. If more than 15 mL of D-positive fetal red blood cells are present in the mother's circulation, more than a single dose of HyperRHO S/D Full Dose is required. Failure to recognize this may result in the administration of an inadequate dose. Although systemic reactions to human immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactic reactions. Pregnancy Category C Animal reproduction studies have not been conducted with Rho(D) Immune Globulin (Human) — HyperRHO® S/D Full Dose. It is also not known whether HyperRHO S/D Full Dose can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HyperRHO S/D Full Dose should begiven to a pregnant woman only if clearly needed. Pediatric Use Safety and effectiveness in the pediatric population have not been established.

WARNINGS For intramuscular use only, do not inject intravenously. In the case of postpartum use, the product is intended for maternal administration. Do not inject the newborn infant. Patients should be observed for at least 20 minutes after administration. Administer with caution to patients who have had prior severe systemic allergic reactions to human immune globulin. RhoGAM / MICRhoGAM contain a small quantity of IgA. There is a potential risk of hypersensitivity in IgA deficient individuals. Patients treated for Rh-incompatible transfusion should be monitored by clinical and laboratory means for signs and symptoms of a hemolytic reaction. Store at 2 to 8°C. Do not store frozen. Do not use after the expiration date printed on the syringe. Use of Plasma Derived Products RhoGAM and MICRhoGAM are made from human plasma and may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing plasma for the presence of certain current virus infections and by using pathogen removal and inactivation techniques during the manufacturing process. All of the above steps are designed to increase product safety by reducing the risk of pathogen transmission. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. All infections thought by a physician possibly to have been transmitted by these products should be reported by the physician or other healthcare provider in the United States to Ortho-Clinical Diagnostics, Inc. at 1-800-421-3311. Outside the United States, the company distributing these products should be contacted. The physician should discuss the risks and benefits of these products with the patient. PRECAUTIONS Laboratory Tests Recovery of anti-D in plasma or serum after injection of RhoGAM or other Rho(D) Immune Globulin (Human) products is highly variable among individuals. Anti-D detection in a patient's plasma is dependent on assay sensitivity and time of sample collection post- injection. Currently there are no requirements or practice standards to test for the presence of anti-D in order to determine adequacy or efficacy of dose following an injection of RhoGAM. The presence of passively acquired anti-D in the maternal serum may cause a positive antibody screening test. This does not preclude further antepartum or postpartum prophylaxis. Some babies born to women given Rho(D) Immune Globulin (Human) antepartum have weakly positive direct antiglobulin (Coombs) tests at birth. Fetal-maternal hemorrhage may cause false blood typing results in the mother. Late in pregnancy or following delivery, there may be sufficient fetal Rh-positive red blood cells in the circulation of the Rh-negative mother to cause a positive antiglobulin test for weak D (Du). In this instance if there is any doubt as to the patient's Rh type, RhoGAM or MICRhoGAM should be administered.9 Use In Specific Populations Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with RhoGAM or MICRhoGAM. The available evidence suggests that Rho(D) Immune Globulin (Human) does not harm the fetus or affect future pregnancies or the reproduction capacity of the maternal recipient.13,14 Rh Blood Type RhoGAM or MICRhoGAM Rho(D) Immune Globulin (Human) should only be administered to Rh-negative patients exposed or potentially exposed to Rh-positive red blood cells to prevent Rh immunization. REFERENCES 9 ACOG practice bulletin. Prevention of Rh D alloimmunization. Number 4, May 1999 (replaces educational bulletin Number 147, October 1990). Clinical management guidelines for obstetrician-gynecologists. American College of Obstetrics and Gynecology. Int J Gynaecol Obstet. 1999; 66(1):63-70. 13 Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-56. 14 Thornton JG, Page C, Foote G, Arthur GR, Tovey LAD, Scott JS. Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin. Brit Med J 1989;298:1671-73.

WARNINGS RhoGAM (rho(d) immune globulin (human)) and MICRhoGAM (rho(d) immune globulin (human)) are made from human plasma. Because these products are made from human blood, they may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections and by removing certain viruses during the manufacturing process. Following fractionation, an additional viral-clearance filtration step is incorporated into the manufacturing process. This filtration step removes viruses via a size-exclusion mechanism utilizing a patented Viresolve 180 ultrafiltration membrane with a defined pore-size distribution of 12-18 nanometers. The filter is inert to the product. This virus removal process has been shown in laboratory spiking studies to reduce the levels of some viruses ranging from18-200 nanometers in size, including enveloped viruses as well as non-enveloped viruses.4 All of the above steps are designed to increase product safety by reducing the risk of transmission of lipid-enveloped and non-lipid-enveloped viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. ALL infections thought by a physician possibly to have been transmitted by these products should be reported by the physician or other healthcare provider in the United States to Ortho-Clinical Diagnostics, Inc. at 1-800-421-3311. Outside the United States, the company distributing these products should be contacted. The physician should discuss the risks and benefits of these products with the patient. RhoGAM (rho(d) immune globulin (human)) and MICRhoGAM (rho(d) immune globulin (human)) are manufactured and distributed by Ortho-Clinical Diagnostics, Inc., Raritan, NJ 08869. PRECAUTIONS For intramuscular use only. Do not inject RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) intravenously. In the case of postpartum use, the product is intended for maternal administration. Do not inject the newborn infant. Patients should be observed for at least 20 minutes after administration. Allergic responses to RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) may occur. Patients should be informed of the early signs of hypersensitivity reactions, including hives, generalized urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. The treatment depends upon the nature and severity of the reaction. RhoGAM (rho(d) immune globulin (human)) and MICRhoGAM (rho(d) immune globulin (human)) contain a small quantity of IgA (less than 15 μg per dose).9 Although high doses of intravenous immunoglobulin containing IgA at levels of 270-720 μg/mL have been given without incident during treatment of patients with high-titered antibodies to IgA,17 the attending physician must weigh the benefit against the potential risks of hypersensitivity reactions. The presence of passively acquired anti-D in the maternal serum may cause a positive antibody screening test. This does not preclude further antepartum or postpartum prophylaxis. Some babies born of women given Rho(D) Immune Globulin (Human) antepartum have weakly positive direct antiglobulin (Coombs) tests at birth. Fetal-maternal hemorrhage may cause false blood typing results in the mother. Late in pregnancy or following delivery, there may be sufficient fetal Rh-positive red blood cells in the circulation of the Rh-negative mother to cause a positive antiglobulin test for weak D (Du). When there is any doubt as to the patient's Rh type, RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM (rho(d) immune globulin (human)) should be administered. Pregnancy Category C Animal reproduction studies have not been conducted with RhoGAM (rho(d) immune globulin (human)) or MICRhoGAM. The available evidence suggests that Rho(D) Immune Globulin (Human) does not harm the fetus or affect future pregnancies or the reproduction capacity of the maternal recipient.18,19 REFERENCES 4. Data on file at Ortho-Clinical Diagnostics, Inc. 9. Data on file at Ortho-Clinical Diagnostics, Inc. 17. Cunningham-Rundles C, Zhuo Z, Mankarious S, Courter S. Long-term use of IgA-depleted intravenous immunoglobulin in immunodeficient subjects with anti-IgA antibodies. J Clin Immunol 1993;13:272-78. 18. Zipursky A, Israels LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245-56. 19. Thornton JG, Page C, Foote G, Arthur GR, Tovey LAD, Scott JS. Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin. Brit Med J 1989;298:1671-73.