Antihemophilic products

Biological products were developed traditionally, before recombinant proteins, as extracts or derivatives of the actual protein from the human body or nature. This approach continues today and Table 15 lists 18 such products, mostly blood derivatives for therapeutic use. Albumin is obtained for cardiovascular volume conditions. A fish protein is harvested for osteoporosis. Igs extracted from blood are available for immunodeficiency conditions, viral infections (hepatitis-B and vaccinia), hemolytic anemia in newborns, and idiopathic thrombocytopenic purpurea. Antihemophilic products are still derived from blood. An antiglobulin is produced for kidney transplant rejection. A collagen product and two botulinum toxin products are used for various facial wrinkle problems and cervical dystonia. A bacterial antigen is formulated to enhance immunity to treat a cancer. 

Along with the production of insulin, many other medical uses have been achieved for recombinant DNA. This includes the production of erythropoetin, a hormone used to stimulate production of red blood cells in anemic people tissue plasminogen activator, an enzyme that dissolves blood clots in heart attack victims and antihemophilic human factor VIII, used to prevent and control bleeding for hemophiliacs. These three important genetically engineered proteins were all cloned in hamster cell cultures. 

H. Other considerations Antihemophilic factor (recombinant) has been designated an orphan product for use in the treatment or prophylaxis of bleeding in hemophilia A, or prophylaxis before surgery. 

Antihemophilic factor, human [FDA for blood-derived product]... 

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). 

Antihemophilic factor [factor VIII, AHF] (Alphanate, Bioclate, Helixate, Hemofil M, Koate-HP, Kogenate, Monoclate, Recombinate, others) Recombinant product. 

Pool, J. G. and Shannon, A. E. (1965). Production of high-potency concentrates of antihemophilic globulin in a closed-bag system. N. Engl. J. Med. 273, 1443-1447. 

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). 

The antihemophilic globulin, the factor absent from the blood in the best-known hemophilia, combines stoichiometrically with a platelet thromboplastic factor, and the two compounds act like precursors, yielding a product itself a precursor. For thromboplastin, the product is prothromboplastin. The platelet thromboplastin component acts like a catalyst consequently, its concentration does not change during the reaction. The prothromboplastin combines with another compound called the plasma-accelerating globulin to yield a new product, namely, thromboplastin. 

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