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HAEMOPHILUS TYPE B CONJUGATE VACCINE

Category Active immunizing agent.

      Haemophilus Type b Conjugate Vaccine is a sterile liquid or freeze-dried preparation of a polysaccharide, derived from a suitable strain of Haemophilus influenzae type b (Hib), covalently bound to a carrier protein. The polysaccharide, polyribosylribitol phosphate (PRP), is a linear copolymer composed of repeated units of 3-β-D-ribofuranosyl-(1→1)-ribitol-5- phosphate [(C10H19O12P)n], with a defined molecular size. The carrier protein, when conjugated to PRP, is capable of inducing a T-cell-dependent B-cell immune response to the polysaccharide.

      The vaccine reconstituted, if necessary as stated on the label, complies with the requirements stated under Vaccines, with the following modifications.

Description Liquid vaccine is clear and colourless.

      Freeze-dried vaccine, when reconstituted, becomes a clear and colourless liquid.

Strengths available 7.5 to 10 μg of haemophilus b capsular polysaccharide bound to 125 μg of an outer membrane protein (OMP) complex of the Neisseria meningitidis, or bound to approximately 20 to 30 μg of tetanus toxoid, or bound to approximately 25 μg of diptheria CRM 197 protein, per 0.5 ml. 

Dose Children under 6 years of age: Intramuscular, 0.5 ml, into the deltoid region; for small children and infants, injection at anterolateral thigh is more preferable.

Contra-indication

1. It is not for intravenous administration.

2. It should not be administered to anyone who developed a reaction to a previous dose.

Warning

1. It may cause soreness, pain or tenderness, erythema, swelling and induration at injection site.

2. Fever, irritability, drowsiness, and anorexia may occur.

3. Risk-benefit should be considered if it is to be used in patients with a prior history of Guillain-Barré syndrome.

Additional information

1. It is not recommended for use in adults and adolescences except for patients with certain chronic conditions associated with an increased risk of Hib disease.

2. Safety and efficacy are not established for use in infants under 6 weeks of age.

Expiration date When stored under the prescribed conditions, the expiration date of liquid vaccine is not later than 2 years and of the freeze-dried vaccine is not later than 3 years, from the date of the last satisfactory test for potency, or shall be based on the stability data of the vaccine.

Labelling Complies with the “General Information for Biological Products”, p. 177. In addition the label on the container states (1) the number of μg of PRP per human dose; (2) the type and nominal amount of carrier protein per single human dose.

Identification The vaccine is identified by a suitable immunochemical method (Appendix 14.5) for PRP.

pH 5.0 to 7.5 (Appendix 4.11).

Antimicrobial preservative Where applicable, determine the amount of antimicrobial preservative by a suitable chemical or physico-chemical method. The content is not less than the minimum amount shown to be effective and not more than 115 per cent of the quantity stated on the label.

Pyrogens Complies with the “Pyrogen Test” (Appendix 8.2), using 1 μg of PRP for a vaccine with diphtheria toxoid or CRM 197 diphtheria protein as carrier; 0.1 μg of PRP for a vaccine with tetanus toxoid as carrier; 0.025 μg of PRP for a vaccine with OMP as carrier, per kg of the rabbit’s weight.

PRP content Not less than 80 per cent of the amount of PRP stated on the label.

      PRP is determined either by assay of ribose or phosphorus, by an immunochemical method (Appendix 14.5) or by anion-exchange liquid chromatography with pulsed amperometric detection (Appendix 3.5).

      FOR RIBOSE

      Test solution Use a volumetric flask with a suitable volume for preparation of a solution containing about 5 mg per ml of dry polysaccharide. Transfer the contents of a container quantitatively to the flask and dilute to volumes with water. Dilute the solution so that the volumes used in the test contain 2.5 to 25 μg of ribose. Introduce 0.20 and 0.40 ml of the diluted solution into tubes in triplicate.

      Reference solution Dissolve 25 mg of ribose in water and dilute to 100.0 ml with the same solvent (stock solution containing 0.25 g per litre of ribose). Immediately before use, dilute 1 ml of the stock solution to 10.0 ml with water (working dilution containing 25 mg per litre of ribose). Introduce 0.10 ml, 0.20 ml, 0.40 ml, 0.60 ml, 0.80 ml, and 1.0 ml of the working dilution into six tubes.

      Prepare a blank using 2 ml of water.

      Make up the volume in each tube to 2 ml with water. Mix and add 2 ml of a 0.05 per cent w/v solution of iron(III) chloride in hydrochloric acid to each tube. Mix and add 0.2 ml of a 10 per cent w/v solution of orcinol in ethanol. Place the tubes in a water-bath for 20 minutes. Cool in iced water.

      Meassure the absorbance (Appendix 2.2) of each solution at 670 nm, using the blank solution in the reference cell. Draw a calibration curve from the absorbance readings for the six reference solutions and the corresponding content of ribose and read from the curve the quantity of ribose in the test solution for each volume tested. Calculate the mean of the three values.

      FOR PHOSPHORUS

      Test solution Use a volumetric flask with a suitable volume for preparation of a solution containing about 5 mg per ml of dry polysaccharide. Transfer the contents of a container quantitatively to the flask and dilute to volume with water. Dilute the solution so that the volume used in the test (1 ml) contains about 6 μg of phosphorus. Transfer 1.0 ml of the solution to a 10-ml ignition tube.

      Reference solutions Dissolve 0.2194 g of potassium dihydrogenphosphate in 500 ml of water to give a solution containing the equivalent of 0.1 mg of phosphorus per ml. Dilute 5.0 ml of the solution to 100.0 ml with water. Introduce 0.5 ml, 1.0 ml and 2.0 ml of the dilute solution into three ignition tubes.

      Prepare a blank solution using 2.0 ml of water in an ignition tube.

      To all the tubes add 0.2 ml of sulfuric acid and heat in an oil-bath at 120º for 1 hour and then at 160º until white fumes appear (about 1 hour). Add 0.1 ml of perchloric acid and heat at 160º until the solution is decolourized (about 90 minutes). Cool and add to each tube 4 ml of water and 4 ml of ammonium molybdate with ascorbic acid TS. Heat in a water-bath at 37º for 90 minutes and cool. Adjust the volume to 10.0 ml with water. The blue colour is stable for several hours.

      Measure the absorbance (Appendix 2.2) of each solution at 820 nm, using the blank solution in the reference cell. Draw a calibration curve with the absorbances of the three reference solutions as a function of the quantity of phosphorus in the solutions and read from the curve the quantity of phosphorus in the test solution.

MONOGRAPHS • HAEMOPHILUS TYPE B CONJUGATE VACCINE
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หมายเหตุ / Note : TP II 2011 PAGE 245-247