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Albumin; Albumin, Human

Category Human blood and blood products (blood volume expander; antihyperbilirubinemic).

         Albumin Solution is an aqueous solution of protein. It is a sterile, nonpyrogenic preparation of albumin obtained by fractionating human plasma that complies with the requirements stated under Plasma for fractionation, p. 193.

         Separation of the albumin solution is carried out under controlled conditions, particularly of pH, ionic strength and temperature, so that in the final product not less than 95 per cent of the total protein is albumin.

Description Clear, slightly viscous liquid. It is almost colourless, yellow, amber or green, depending on protein concentration.

Strengths available 5, 20 and 25 per cent w/v (total protein).

Dose Intravenous infusion, as prescribed by the physician.

Contra-indication It is contra-indicated in patients with severe anemia or cardiac failure.

Warning

         1. Adverse reactions (which may be caused by allergy or protein overload resulting from high dosage or repeated administrations) include fever, chills, nausea, vomiting, increased salivation, and urticaria. Variable effects on blood pressure, heart rate, and respiration may also occur.

         2. It should be used with caution in patients with hypertension or low cardiac reserve.

         3. The possibility that human albumin solutions may contain aluminium as a contaminant, which could accumulate in patients with impaired renal function, should be considered.

         4. Sterile water for injection must not be used as a diluent for 20 and 25 per cent w/v solutions of albumin, because of the risk of potentially life-threatening hemolysis.

Additional information

         1. It contains no blood group isoagglutinins and, therefore, may be given without regard to the blood group of the patient.

         2. Transfusions of whole blood or packed red cell concentrate may be necessary following administration of large volumes of albumin to restore hemoglobin concentration and to prevent anemia.

         3. It may be administered with plasma, packed red cells, or whole blood; however, albumin should not be added directly to any of these three components, except when used as a red blood cell resuspension medium.

Expiration date When stated to be stored at a temperature not higher than 25º, the expiration date is not more than 3 years; or at 2º to 8º, it is not more than 5 years.

Packaging and storage Albumin Solution shall be kept in tightly closed containers, and stored at the temperature recommended by the manufacturer or indicated on the label, protected from light; avoid freezing.

Labelling Complies with the “General Information for Biological Products”, p. 177. In addition, the label on the container states (1) the volume in the container; (2) the total amount of protein in the container expressed in g per litre or as a percentage; (3) the concentration of sodium expressed in mmol per litre; (4) the names and concentrations of stabilizing agents and of any other added substances present in the final solution; (5) that the solution must not be used if it is cloudy or contains a deposit; (6) that, once the container has been penetrated, the contents should be used within 4 hours and any unused preparation discarded; (7) that a filter is to be used in the administration set; (8) either that the preparation is suitable for administration to patients undergoing analysis and to premature infants or that it is not intended for such use.

Identification

         A. Using an antiserum specific to human plasma proteins and a range of antisera specific to the plasma proteins of each species of domestic animal commonly used in the preparation of materials of biological origin, carry out precipitation tests on the preparation being examined. The preparation contains proteins of human origin and gives negative results with antisera specific to plasma proteins of other species. 

         B. Examine by a suitable immunoelectrophoresis technique. Using antiserum to normal human serum, compare normal human serum and the preparation being examined, both diluted to contain 1 per cent w/v of protein. The main component of the preparation being examined corresponds to the main component of the normal human serum. The solution may show the presence of small quantities of other plasma proteins.

pH 6.4 to 7.4, when diluted with saline TS to produce a solution containing 1 per cent w/v of protein (Appendix 4.11).

Aluminium Not more than 200 μg per litre when determined as described in the “Atomic Spectrometry: Emission and Absorption” (Appendix 2.3). Measure at 309.3 nm and use aluminium standard solution (10 ppm Al), suitably diluted with water, as the standard solution.

Potassium Not more than 0.05 mmol of K per g of protein when determined as described in the “Atomic Spectrometry: Emission and Absorption” (Appendix 2.3). Measure at 766.5 nm and use potassium solution Asp, suitably diluted with water, as the standard solution.

Sodium 95 to 105 per cent of the content of Na stated on the label and, in any case, not more than 160 mmol of Na per litre when determined as described in the “Atomic Spectrometry: Emission and Absorption” (Appendix 2.3). Measure at 589 nm and use sodium solution Asp, suitably diluted with water, as the standard solution.

Haem Dilute with sufficient saline TS to produce a solution containing 1.0 per cent w/v of protein. The absorbance of the resulting solution at 403 nm is not more than 0.15 (Appendix 2.2). Use water in the reference cell.

Prekallikrein activator Not more than 35 IU per ml (Appendix 14.2.2).

Distribution of molecular size Carry out the test as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

         Mobile phase Dissolve and dilute 4.873 g of disodium hydrogenphosphate dihydrate, 1.741 g of sodium dihydrogenphosphate monohydrate, 11.688 g of sodium chloride and 50 mg of sodium azide with water to 1000.0 ml.

         Test preparation Dilute the preparation being examined with saline TS to a concentration suitable for the chromatographic system used. A concentration in the range of 0.4 to 1.2 per cent w/v of protein and the injection of 50 to 600 μg of protein are usually suitable.

         Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (60 cm × 7.5 mm) packed with hydrophilic silica gel (3 to 10 μm), (b) Mobile phase at a flow rate of about 0.5 ml per minute and (c) an ultraviolet photometer set at 280 nm.

         The peak corresponding to polymers and aggregates is located in the part of the chromatogram representing the void volume. The area of this peak divided by 2 is not more than 5 per cent of the total area of the chromatogram.

Protein composition Carry out the determination as described in the “Cellulose Acetate Electrophoresis” (Method II, Appendix 3.7), using one strip of cellulose acetate for each solution. For solution (A) dilute the preparation being examined with saline TS to produce a solution containing 2 per cent w/v of protein. For solution (B) dilute Albumin Solution (Human Albumin) for Electrophoresis RS with saline TS to produce a solution containing 2 per cent w/v of protein. In the strips prepared with solution (A) not more than 5 per cent of the protein is contained in bands other than the principal band. The test is not valid unless the proportion of protein in the principal band in the strip prepared with solution (B) is within the limits stated in the leaflet supplied with Human Albumin for Electrophoresis RS.

Total protein Not less than 95 per cent and not more than 105 per cent of the quantity of protein stated on the label. Dilute the preparation being examined with saline TS to obtain a solution containing about 15 mg of protein in 2 ml. To 2.0 ml of the resulting solution in a round-bottomed centrifuge tube add 2 ml of a 7.5 per cent w/v solution of sodium molybdate and 2 ml of a mixture of 30 volumes of water and 1 volume of nitrogen-free sulfuric acid. Shake, centrifuge for 5 minutes, decant the supernatant liquid, and allow the inverted tube to drain on filter paper. Using the residue thus obtained, carry out the “Determination of Nitrogen” (Method II, Appendix 6.7), and calculate the content of protein by multiplying the result by 6.25.

Pyrogens or Bacterial endotoxins Complies with the “Pyrogen Test” (Appendix 8.2) or, preferably and where justified and authorized, with a validated in vitro test such as the “Test for Bacterial Endotoxins” (Appendix 8.5).

         For the pyrogen test, for a solution containing 3.5 to 5.0 per cent w/v of protein, use 10 ml of the preparation per kg of the rabbit’s weight. For a solution containing 15.0 to 25.0 per cent w/v of protein, use 5 ml of the preparation per kg of the rabbit’s weight.

         Where the bacterial endotoxin test is used, it contains less than 0.5 Endotoxin Unit per ml for solutions with a protein content more than 5.0 per cent w/v solution, less than 1.3 Endotoxin Units per ml for solutions with a protein content more than 5.0 per cent w/v solution but not more than 20.0 per cent w/v solution, and less than 1.7 Endotoxin Units per ml for solutions with a protein content more than 20.0 per cent w/v solution but not more than 25.0 per cent w/v solution.

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