"The U.S. Food and Drug Administration today approved Alprolix, Coagulation Factor IX (Recombinant), Fc Fusion Protein, for use in adults and children who have Hemophilia B. Alprolix is the first Hemophilia B treatment designed to require less fre"...
[Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] for Intravenous Injection
ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] is a purified glycoprotein consisting of 2,332 amino acids that is synthesized by a genetically engineered CHO cell line. In culture, the CHO cell line expresses rAHF into the cell culture medium. The rAHF is purified from the culture medium using a series of chromatography columns. The purification process includes an immunoaffinity chromatography step in which a monoclonal antibody directed against Factor VIII is employed to selectively isolate the rAHF from the medium. The cell culture and purification processes used in the manufacture of ADVATE employ no additives of human or animal origin. The production process includes a dedicated, viral inactivation solvent-detergent treatment step. The rAHF synthesized by the CHO cells has the same biological effects on clotting as human Antihemophilic Factor [hAHF]. Structurally the recombinant protein has a similar combination of heterogeneous heavy and light chains as found in AHF (Human).
ADVATE is formulated as a sterile, non-pyrogenic, white to off-white powder for intravenous injection. When reconstituted with the provided Sterile Water for Injection, USP, the product contains the following stabilizers and excipients in targeted amounts:
Table 5 : Approximate Concentration of Stabilizer and
Excipient after Reconstitution
|Stabilizer and Excipient||5 mL Reconstitution (for 250, 500, 1000, 1500, 2000, 3000, 4000 IU) Target||2 mL Reconstitution (for 250, 500, 1000, 1500 IU) Target|
|Tris (hydroxymethyl) aminomethane||10 mM||25 mM|
|Calcium Chloride||1.7 mM||4.2 mM|
|Mannitol||3.2% (w/v)||8% (w/v)|
|Sodium Chloride||90mM||225 mM|
|α, α-Trehalose||0.8% (w/v)||2% (w/v)|
|Histidine||10 mM||25 mM|
|Glutathione (Reduced)||0.08 mg/mL||0.2 mg/mL|
|Polysorbate 80||0.01% (w/v)||0.025% (w/v)|
ADVATE is available in single-dose vials that contain nominally 250, 500, 1000, 1500, 2000, 3000 or 4000 International Units (IU) per vial. The product contains the following stabilizers and excipients: mannitol, trehalose, sodium chloride, histidine, Tris, calcium chloride, polysorbate 80, and glutathione. VWF is coexpressed with Factor VIII and helps to stabilize it in culture. The final product contains no more than 2 ng VWF/IU rAHF, which will not have any clinically relevant effect in patients with von Willebrand disease. The product contains no preservative.
Each vial of ADVATE is labeled with the rAHF activity expressed in International Units per vial. Biological potency is determined by an in vitro assay, which employs a Factor VIII concentrate standard that is referenced to a WHO International Standard for Factor VIII concentrates. One International Unit, as defined by the WHO standard for blood coagulation Factor VIII, human, is approximately equal to the level of Factor VIII activity found in 1 mL of fresh pooled human plasma. The specific activity of ADVATE is 4000 to 10000 International Units per milligram of protein.
Last reviewed on RxList: 4/4/2014
This monograph has been modified to include the generic and brand name in many instances.
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