Antihemophilic factor stability

The PEG could stabilize proteins by two different temperature-dependent mechanisms. At lower temperatures, it is preferentially excluded from the protein surface but has been shown to interact with the unfolded form of the protein at higher temperatures, given its amphipathic nature (57). Thus, at lower temperatures, it may protect proteins via the mechanism of preferential exclusion, but at higher temperatures possibly by reducing the number of productive collisions between unfolded molecules. PEG is also a cryoprotectant and has been employed in Recombinate, a lyophilized formulation of recombinant Antihemophilic Factor, which utilizes PEG 3350 at a concentration of 1.5mg/mL. The low-molecular weight liquid PEGs (PEG 300-600) can be contaminated with peroxides and cause protein oxidation. If used, the peroxide content in the raw material must be minimized and controlled throughout its shelf life. The same holds true for polysorbates (discussed below). 

Figure 5.3. Intrinsic and extrinsic blood clotting cascades. Factor I, fibrinogen Factor II, prothrombin (vitamin K-dependent) Factor III, thromboplastin Factor V, proac-celerin Factor VII, proconvertin (vitamin K-dependent) Factor VIII, antihemophilic factor Factor IX, Christmas factor (vitamin K-dependent) Factor X, Stnart factor (vitamin K-dependent) Factor XI, plasma thromboplastin Factor XII, Hageman factor Factor XIII, fibrin-stabilizing factor and Factor XIV, protein C (vitamin K-dependent). What was at one time called Factor IV is calcinm no factor has been assigned nnmber VI.

Recombinant factor VIII is stabilized with human serum albumin during purification and in the final product. Although albumin has an excellent safety record and no recombinant antihemophilic factors have been associated with virus transmission, there is still concern about the safety of products that contain human- or animal-derived components (50). A second-generation recombinant factor VIII product has been developed with a modified manufacturing process and a formulation in which the recombinant factor VIII is stabilized by sucrose instead of albumin (50). 

Bl. Baumgarten, W., Sanders, B. E., Belkin, B. D., Pagenkemper, F. E., Albers, W. G., and Ciminera, J. L., Antihemophilic factor its presence in fibrinogen, assay problems and the stability of lyophilized AHF-Fibrinogen preparations. Thromh. Diath. Haemorrhag. 9, 354r-367 (1963). 

NZ BAY-14-2222 antihemophilic Kogenate FS Helixate FS, Kogenate SF Human recombinant factor VIII expressed in baby hamster kidney cells and purified by modified chromatography and then stabilized with sucrose Hemophilia... 

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