MONOCLATE-P- antihemophilic factor human
CSL Behring LLC
Rx only
DESCRIPTION
Antihemophilic Factor (Human), Monoclate-P� , Factor VIII:C Pasteurized, Monoclonal Antibody Purified, is a sterile, stable, lyophilized concentrate of Factor VIII:C with reduced amounts of VWF:Ag and purified of extraneous plasma-derived protein by use of affinity chromatography. A murine monoclonal antibody to VWF:Ag is used as an affinity ligand to first isolate the Factor VIII Complex. Factor VIII:C is then dissociated from VWF:Ag, recovered, formulated and provided as a sterile lyophilized powder.1,2,3 The concentrate as formulated contains Albumin (Human) as a stabilizer, resulting in a concentrate with a specific activity between 4 and 10 units/mg of total protein. In the absence of this added Albumin (Human) stabilizer, specific activity has been determined to exceed 3000 units/mg of protein.4 Monoclate-P� has been prepared from pooled human plasma and is intended for use in therapy of classical hemophilia (Hemophilia A).
All Source Plasma used in the manufacture of this product was tested by FDA-licensed Nucleic Acid Testing (NAT) for HBV, HCV, and HIV-1 and found to be nonreactive (negative).
This concentrate has been pasteurized by heating at 60�C for 10 hours in aqueous solution form during its manufacture in order to further reduce the risk of viral transmission.5 However, no procedure has been shown to be totally effective in removing viral infectivity from coagulant factor concentrates (see CLINICAL PHARMACOLOGY and WARNINGS).
Monoclate-P� is a highly purified preparation of Factor VIII:C. When stored as directed, it will maintain its labeled potency for the period indicated on the container and package labels.6,7
Upon reconstitution of the 250, 500 and 1000 IU concentrates, a clear, colorless solution is obtained, containing 50 to 150 times as much Factor VIII:C as does an equal volume of plasma.
Upon reconstitution of the 1500 IU concentrate, a clear, colorless solution is obtained, containing 120 to 180 times as much Factor VIII:C as does an equal volume of plasma.
Each vial contains the labeled amount of antihemophilic factor (AHF) activity as expressed in terms of International Units (IU) of antihemophilic activity. One unit of antihemophilic activity is equivalent to that quantity of AHF present in one mL of normal human plasma. When reconstituted as recommended, the resulting solution contains approximately 300 to 450 millimoles of sodium ions per liter and has 2 to 3 times the tonicity of saline. It contains approximately 2-5 millimoles of calcium ions per liter, contributed as calcium chloride, approximately 1 to 2% Albumin (Human), 0.8% mannitol, and 1.2 mM histidine. The pH is adjusted with hydrochloric acid and/or sodium hydroxide. Monoclate-P� also contains trace amounts (≤50 ng per 100 IU of AHF) of the murine monoclonal antibody used in its purification (see CLINICAL PHARMACOLOGY).
Monoclate-P� is to be administered only intravenously.
CLINICAL PHARMACOLOGY
Factor VIII:C is the coagulant portion of the Factor VIII complex circulating in plasma. It is noncovalently associated with the von Willebrand protein responsible for von Willebrand factor activity. These two proteins have distinct biochemical and immunological properties and are under separate genetic control. Factor VIII:C acts as a cofactor for Factor IX to activate Factor X in the intrinsic pathway of blood coagulation.8 Hemophilia A, a hereditary disorder of blood coagulation due to decreased levels of Factor VIII:C, results in profuse bleeding into joints, muscles or internal organs as a result of a trauma. Monoclate-P� provides an increase in plasma levels of AHF, thereby enabling temporary correction of Hemophilia A bleeding.