Art. 3 Protocol bij de Europese Overeenkomst betreffende de uitwisseling van geneesmiddelen van menselijke oorsprong, zoals gewijzigd — Human Albumin and Human Plasma Protein Fraction

Human Albumin and Human Plasma Protein Fraction are preparations of that protein component which forms about 60% of the total protein mass in the plasma of Whole Human Blood. The method of preparation used shall be one which produces a material meeting the requirements herein described. Regardless of whether the final product is liquid or dried, the preparation, after the addition of a suitable stabilising agent or agents, must have been heated in the liquid state in the final container at 60° C ± 0.5° C for 10 hours, in order to inactivate the agent causing serum hepatitis. During preparation no antiseptic or bacteriostatic substance shall be added. In preparations of Human Albumin, not less than 95% of the mass of the proteins present shall be albumin. In preparations of Human Plasma Protein Fraction, not less than 85% of the protein mass shall be albumin. In both preparations, more than 10 milligram immunoglobulin G per gram product shall be present. When the final product is freeze-dried, it must contain not less than 950 milligram of protein per gram product. When Human Plasma Protein Fraction is prepared as a solution it shall have a total protein concentration between 45 and 50 grams per litre. When Human Albumin is prepared as a solution it shall have a total protein concentration not less than 45 gram per litre. Solubility of the dried product - Add water to the recommended volume; the dried preparation must be completely soluble. Stability - By comparison of the solutions before and after heat treatment no evidence of significant denaturation of the proteins in solution shall have been detected as estimated by viscosity and turbidity measurements, ultracentrifugation and electrophoresis. The solution shall be substantially free from visible particles after heating at 57° C and after agitation in a mechanical shaker for 6 hours at this temperature. Identification By precipitation tests with specific antisera, both preparations must be shown to contain only human plasma proteins. By electrophoresis, using the moving boundary technique under acceptable and appropriate conditions, it must be shown that the protein fraction having the mobility of the albumin component of normal human plasma, is not less than 95% of the protein mass in preparations of Human Albumin, or not less than 85% of the protein mass in preparations of Human Plasma Protein Fraction. Sodium content and sodium concentration - The sodium content of salt-poor Human Albumin must not exceed 0.61 millimole per gram of albumin. In other preparations of Human Albumin and in Human Plasma Protein Fraction, the sodium concentration must not exceed 0.15 mole per litre of solution or reconstituted dried product. Potassium concentration - The potassium concentration of Human Plasma Protein Fraction must not exceed 2 millimole per litre of solution or reconstituted dried product. Acidity - The pH of either preparation shall be 6.8 + 0.2 when measured at a temperature of 15 to 25° C in a solution diluted to a protein concentration of 10 gram per litre by means of a solution containing 0.15 mole sodium chloride per litre. Loss of mass on drying - Dried preparations, when dried over phosphorus pentoxide at a pressure not exceeding 0.02 mm of mercury for 24 hours, must not lose more than 0.5% of their weight. Sterility - The final product shall be sterile when examined by a suitable bacteriological method. Storage - Dried Human Albumin must be kept in an atmosphere of nitrogen or in a vacuum in a sterile container, sealed so as to exclude micro-organisms and, as far as possible, moisture, protected from light and stored at a temperature below 20° C. Solutions of Human Albumin and Human Plasma Protein Fraction must be kept in sterile containers, sealed so as to exclude micro-organisms, protected from light and stored at a temperature of 4° to6°C. Labelling - The label on the container shall give all the information shown on the appropriate model label (Annex 4). For solutions, the date of preparation is the date of heat treatment in the final container.

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