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Category Active immunizing agent.

      Inactivated Influenza Vaccine (Surface Antigen, Virosome) is a sterile, aqueous suspension of a strain or strains of influenza virus, type A or B, or a mixture of strains of the two types grown individually in embryonated chicken eggs, inactivated and treated so that the preparation consists predominantly of hemagglutinin and neuraminidase antigens reconstituted to virosomes with phospholipids and without diminishing the antigenic properties of the antigens.

      The vaccine complies with the requirements stated under Vaccines, with the following modifications.

Description Slightly opalescent liquid.

Strength available Each 0.5 ml dose contains not less than 15 μg hemagglutinin antigen for each strain.

Dose Adults and children 3 years of age and older: Intramuscular, at deltoid region, 0.5 ml.

      Children under 3 years of age and infants 6 months of age and older: Intramuscular, at anterolateral aspect of the thigh, 0.25 ml.

      (Note Dose should be repeated at least 4 weeks if the children younger than 8 years of age has not been previously vaccinated.)

Contra-indication

1. It is contra-indicated in individuals with a history of hypersensitivity to egg proteins.

2. It is not for intravenous administration.

Warning​

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

2. Fever, malaise, myalgia, and other systemic manifestations may occur.

          3. Immunization should be delayed in persons with an active neurological disorder characterized by changing neurological findings, but can be initiated when the disease process has been stabilized.

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

5. It is not recommended for infants under 6 months of age.

Expiration date When stored under the prescribed conditions, the expiration date should not exceed 1 year from the date of issue stated by the manufacturer.

Labelling Complies with the “General Information for Biological Products” p. 177. In addition the label on the container states (1) that the vaccine has been prepared in eggs; (2) the strain or strains of influenza virus used to prepare the vaccine; (3) the method of inactivation; (4) the hemagglutinin content in micrograms per virus strain per dose; (5) the maximum amount of ovalbumin; (6) the season during which the vaccine is intended to protect.

Identification The identity of the hemagglutinins in the vaccine should be determined by an immunological technique, such as immunodiffusion or hemagglutinin inhibition, using the appropriate specific immune serum.

Residual infectious virus Inoculate 0.2 ml of the vaccine into the allantoic cavity of each of 10 fertilized eggs and incubate at 35º±2º for 3 days. The test is not valid unless at least 8 of the 10 embryos survive. Harvest 0.5 ml of the allantoic fluid from each surviving embryo and pool the fluids. Inoculate 0.2 ml of the pooled fluid into a further 10 fertilized eggs and incubate at 35º±2º for 3 days. The test is not valid unless at least 8 of the 10 embryos survive. Harvest about 0.1 ml of the allantoic fluid from each surviving embryo and examine each individual harvest for live virus by a hemagglutination test. If hemagglutination is found for any of the fluids, carry out for that fluid a further passage in eggs and test for hemagglutination, hemagglutinin activity should not be detected in these new groups of eggs.

pH 6.5 to 7.8 (Appendix 4.11).

Phospholipid The content and identity of the phospholipids is determined by a suitable immunochemical (Appendix 14.5) or physico-chemical method.

Ratio of hemagglutinin to phospholipid The ratio of hemagglutinin content to phospholipid content is within the limits approved for the particular product.

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

Ovalbumin Not more than the quantity stated on the label and in any case not more than 1 μg per human dose, determined by a suitable immunochemical method (Appendix 14.5) using a suitable reference preparation of ovalbumin.

Total protein Not more than 40 μg of protein other than hemagglutinin per virus strain per human dose and not more than 120 μg of protein other than hemagglutinin per human dose. Carry out the test as described in the “Determination of Nitrogen” (Method III, Appendix 6.7).

Virosome size distribution The size of the virosomes, determined by a suitable method such as laser light scattering, is not less than 100 nm and not more than 500 nm.

Bacterial endotoxins When tested as described in the “Test for Bacterial Endotoxins” (Appendix 8.5), it contains less than 100 Endotoxin Units per single human dose.

Assay Determine the content of hemagglutinin antigen by an immunodiffusion test (Appendix 14.5), by comparison with the National or International Reference Preparation of Influenza Hemagglutinin. Carry out the test at 20º to 25º. Each dose contains 15 μg of hemagglutinin of each strain of virus used in the preparation of the vaccine. The confidence limits (P = 0.95) are not less than 80 per cent and not more than 125 per cent of the estimated hemagglutinin antigen content. The lower confidence limit (P = 0.95) is not less than 80 per cent of the amount stated on the label for each strain.