Antihemophilic Factor (Human)
Factor VIII:C Pasteurized Monoclonal Antibody Purified
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
Monoclate-P® is a highly purifi ed 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 I.U. 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 I.U. 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 (I.U.) 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 I.U. of AHF) of the murine
monoclonal antibody used in its purification (see CLINICAL PHARMACOLOGY).
Monoclate-P® is to be administered only intravenously.
1. W. Terry, A. Schreiber, C. Tarr, M. Hrinda, W. Curry
and F. Feldman, Human Factor VIII:C Produced Using Monoclonal Antibodies, in
Research in Clinic and Laboratory, Vol. XVI, (#1), 202 (1986) from the XVIIth
International Congress of the World Federation of Hemophilia.
2. A. B. Schreiber, The Preclinical Characterization of
Monoclate Factor VIII C Antihemophilic Factor Human, Semin Hematol 25 (2 Suppl.
1), 1988, pp. 27-32.
3. E. Berntorp and I.M. Nilsson, Biochemical Properties
of Human Factor VIII C Monoclate Purified Using Monoclonal Antibody to VWF,
Thromb Res O (Suppl. 7), 1987, p. 60, from the Satellite Symposia of the XIth
International Congress on Thrombosis and Haemostasis, Brussels, Belgium, July
4. S. Chandra, C.C. Huang, R.L. Weeks, K. Beatty and F. Feldman,
Purity of a Factor VIII:C Preparation (Monoclate) Manufactured by Monoclonal
Immunoaffi nity Chromatography Technique, from the XVIII International Congress
of the World Federation of Hemophilia, May 1988.
5. B. Spire, D. Dormont, F. Barre-Sinousii, L.
Montagnier, and J.C. Chermann, Inactivation of Lymphadenopathy Associated Virus
by Heat, Gamma Rays, and Ultraviolet Light, Lancet, Jan. 26, 1985, p. 188.
6. F. Feldman, R. Kleszynski, L. Ho, R. Kling, S. Chandra
and C.C. Huang, Validation of Coagulation Test Methods for Evaluation of
Monoclate (Factor VIII:C) Potencies, from the XVIII International Congress of
the World Federation of Hemophilia, May 1988.
7. S. Chandra, C.C. Huang, L. Ho, R. Kling, R.L. Weeks
and F. Feldman, Studies on the Stability of Factor VIII:C (Monoclate) in
Lyophilized and Solution Form, from the XVIII International Congress of the
World Federation of Hemophilia, May 1988.