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HEPATITIS A VACCINE, INACTIVATED

Hepatitis A Vaccine (Inactivated, Adsorbed)

Category Active immunizing agent.

      Inactivated Hepatitis A Vaccine is a suspension consisting of a suitable strain of hepatitis A virus (HAV) grown in cell cultures, inactivated by a validated method and adsorbed onto suitable adjuvant(s), such as aluminium hydroxide or hydrated aluminium phosphate.

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

Description Whitish turbid suspension.

Strengths available 50 units of viral antigen per ml (0.5 ml or 1 ml per vial); 1440 enzyme linked immunosorbent assay (ELISA) units of viral antigen per ml (0.5 ml or 1 ml per vial).

Dose Intramuscular, at deltoid region.

      Adults over 18 years: 50 units or 1440 ELISA units, the volume injected usually not exceeding 1 ml.

      Adults 18 years of age and under: 25 units or 720 ELISA units, the volume injected usually not exceeding 0.5 ml.

      Children 2 years of age and over: 25 units or 720 ELISA units, the volume injected usually not exceeding 0.5 ml.

Contra-indication

1. It is contra-indicated in individuals with hypersensitivity to any component of the vaccine.

2. It is not for intravenous administration.

Warning

1. It may cause soreness, tenderness or warmth at the injection site.

2. Anorexia, fever, headache or malaise may occur.

          3. It should be used with caution in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or individuals receiving anticoagulant therapy since bleeding may occur following intramuscular administration of the drug.

4. It should not be administered in the gluteal region since administration at this site may result in suboptimal response.

5. It may not prevent hepatitis A infection in individuals who have an unrecognized hepatitis A infection at the time of vaccination.

Additional information

1. It is well tolerated and highly immunogenic and effective in children 2 years of age and older.

          2. Active immunization against hepatitis A may be less effective in immunocompromized individuals and in individuals receiving immunosuppressive therapy since the immune response to the vaccine may be decreased.

3. If it is administered concurrently with any routine childhood vaccines, it should be administered at a different site using a separate syringe.

Expiration date When stored under the prescribed conditions, the expiration date is not later than 3 years from the date of the last satisfactory test for potency.

Labelling Complies with the “General Information for Biological Products” p. 177. In addition the label on the container states (1) the biological origin of the cells used for the preparation of the vaccine; (2) the virus strain used for the production of the vaccine; (3) the method used for inactivating the virus; (4) the nature and amount of adjuvant(s) and preservative present.

Identification The vaccine is shown to contain hepatitis A virus antigen by a suitable immunochemical method (Appendix 14.5) using specific antibodies or by the in vivo assay.

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

Bacterial endotoxins When tested as described in the “Test for Bacterial Endotoxins” (Appendix 8.5), it contains not more than 2 Endotoxin Units per single human dose.

Assay

      The assay of Inactivated Hepatitis A Vaccine is carried out either in vivo, by comparing in given conditions its capacity to induce specific antibodies in mice with the same capacity of a reference preparation, or in vitro, by an immunochemical determination of the antigen content.

      IN VIVO ASSAY

      The test in mice shown below is given as an example of a method that has been found suitable for a given vaccine; other validated methods may also be used.

      Selection and distribution of the test animals Use in the test healthy mice from the same stock, about 5 weeks old and from a strain shown to be suitable. Use animals of the same sex. Distribute the animals in at least seven equal groups of a number suitable for the requirements of the assay.

      Determination of potency of the vaccine to be examined Using saline TS containing the aluminium adjuvant used for the vaccine or another appropriate diluent, prepare at least three dilutions of the vaccine to be examined and matching dilutions of the reference preparation. Allocate the dilutions one to each of the groups of animals and inject subcutaneously not more than 1.0 ml of each dilution into each animal in the group to which that dilution is allocated. Maintain a group of unvaccinated controls, injected subcutaneously with the same volume of diluent. After 28 to 32 days, anaesthetize and bleed all animals, keeping the individual sera separate. Assay the individual sera for specific antibodies against hepatitis A virus by a suitable immunochemical method (Appendix 14.5).

      Calculations Carry out the calculations by the “Statistical Analysis of Results of Biological Assay and Tests” (Quantal response, Appendix 9).

      From the distribution of reaction levels measured on all the sera in the unvaccinated group, determine the maximum reaction level that can be expected to occur in an unvaccinated animal for that particular assay. Any response in vaccinated animals that exceeds this level is by definition a seroconversion.

      Make a suitable transformation of the percentage of animals showing seroconversion in each group (for example, a probit transformation) and analyze the data according to a parallel-line log dose-response model. Determine the potency of the test preparation relative to the reference preparation.

      Validity conditions The test is not valid unless:

– for both the test and the reference vaccine, the ED50 lies between the smallest and the largest doses given to the animals,

– the statistical analysis shows no significant deviation from linearity or parallelism,

– the confidence limits (P = 0.95) are not less than 33 per cent and not more than 300 per cent of the estimated potency

      Potency requirement The upper confidence limit (P = 0.95) of the estimated relative potency is not less than 1.0.

      IN VITRO ASSAY

      Carry out the “Immunochemical Method” (Appendix 14.5) for determination of antigen content with acceptance criteria validated against the in vivo test.

      The acceptance criteria are approved for a given reference preparation by the competent authority in the light of the validation data.

 

MONOGRAPHS • HEPATITIS A VACCINE, INACTIVATED
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หมายเหตุ / Note : TP II 2011 PAGE 247-248