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Human Coagulation Factor VIII (rDNA)

Category Human blood and blood products (coagulant, antihemorrhagic agent).

          Dried Factor VIII (rDNA) is a freeze-dried preparation of glycoproteins having the same activity as coagulation factor VIII in human plasma.

          Human coagulation factor VIII circulates in plasma mainly as a two-chain glycosylated protein with one heavy chain (relative molecular weight of about 200,000) and one light chain (relative molecular weight 80,000) held together by divalent metal ions. Dried Factor VIII (rDNA) is prepared as full-length factor VIII (octocog alfa), or as a shortened two-chain structure (relative molecular weights 90,000 and 80,000), in which the B-domain has been deleted from the heavy chain (moroctocog alfa).

          Full-length human rDNA Factor VIII contains 25 potential N-glycosylation sites, 19 in the B domain of the heavy chain, three in the remaining part of the heavy chain (relative molecular weight 90,000) and three in the light chain (relative molecular weight 80,000). The different products are characterized by their molecular size and post-translational modification and/or other modifications.

          The specific activity is not less than 2000 IU of factor VIII:C per milligram of total protein before the addition of any protein stabilizer, and varies depending on purity and the type of modification of molecular structure of factor VIII.

Description White or slightly yellow powder or friable mass.

Strengths available 50, 62.5, 100, 125, 200, 250, 300, 400, 500 and 600 IU per ml.

Dose Intravenous infusion, as prescribed by the physician.

Contra-indication It is contra-indicated in patients with hypersensitivity to mouse, hamster, or bovine protein, or to porcine or murine factor.

Warning

1. It is not indicated in the treatment of von Willebrand’s disease.

2. Adverse local effects, including burning, pruritus, rash, and erythema may occur.

          3. Systemic effects, including dizziness, lightheadedness, nausea, facial flushing, rash, pruritus, urticaria, rhinitis, depersonalization, chest discomfort, chest tightness with dyspnea, mouth dryness, cold feet, unpleasant, unusual, or metallic taste in the mouth, and a slight increase or decrease in blood pressure may occur.

Expiration date When stored under the prescribed condition, the expiration date is not later than 2 years from the date of the last satisfactory test for potency.

Packaging and storage Dried Factor VIII (rDNA) shall be kept in tightly closed containers, protected from light and stored at a temperature of 2º to 8º.

Labelling Complies with the “General Information for Biological Products”, p. 177. In addition, the label on the container states (1) the content of factor VIII expressed in International Units per container; (2) the name and amount of any added substance; (3) the composition and volume of the liquid to be used for reconstitution.

Identification

A. The assay for factor VIII contributes to the identification of the preparation.

B. The distribution of characteristic peptide bands corresponds with that of the manufacturer’s reference preparation (SDS-PAGE or Western blot, Appendix 14.5).

pH 6.5 to 7.5 (Appendix 4.11).

Osmolality Not less than 240 mOsmol/kg (Appendix 4.35).

Solubility test Reconstitute the solution as stated on the label. The preparation dissolves completely under gentle swirling within 5 minutes at 20º to 25º, giving a clear or slightly opalescent solution.

Water Not more than 3.0 per cent w/w (Karl Fischer Method, Appendix 4.12). Add a suitable volume of anhydrous methanol to the container of the preparation to be examined, shake, allow to stand and carry out the determination on a known volume of the supernatant liquid.

Bacterial endotoxins When tested as described in the “Test for Bacterial Endotoxins” (Appendix 8.5), it contains less than 3 Endotoxin Units per 100 IU of factor VIII activity.

Sterility Complies with the “Sterility Test” (Appendix 10.1).

Assay Carry out the “Biological Assay of Human Coagulation Factor VIII” (Appendix 15.1.3). The estimated potency is not less than 80 per cent and not more than 125 per cent of the stated potency. The confidence limits (P = 0.95) are not less than 80 per cent and not more than 120 per cent of the estimated potency.