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BCG Vaccine

Category Active immunizing agent.

      Freeze-dried BCG Vaccine is a preparation of live bacteria derived from a culture of the bacillus Calmette and Guérin Strain of Mycobacterium tuberculosis var bovis whose capacity to protect against tuberculosis has been established.

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

Description Freeze-dried BCG Vaccine is a white to offwhite dried mass having the characteristic texture of material dried in the frozen state. When reconstituted, it becomes a whitish or pale yellowish turbid liquid.

Strengths available 2 × 10⁶ to 26 × 10⁶ and 1 × 10⁶ to 33 × 10⁶ CFU of Bacillus Calmette-Guérin per ml.

Dose Intracutaneous, 0.1 or 0.05 ml as state on the label.

Contra-indication

      1. It is contra-indicated in individuals with immunosuppression, including those with hypogammaglobulinemia, congenital immunodeficiency, sarcoidosis, leukemia, lymphoma, and generalized malignancy.

      2. It is contra-indicated in HIV infected, severe immune deficiency syndrome or immunocompromised infants, children or adults.

      3. It is contra-indicated in individuals in whom immunologic responses have been suppressed because of prolonged treatment with immunosuppressive therapy (e.g., corticosteroids, certain antineoplastic agents, alkylating agents, antimetabolites, radiation therapy).

      4. It is contra-indicated in individuals with a positive tuberculin skin test, individuals with recent smallpox immunizations, and burn patients.

      5. It is contra-indicated in individuals with hypersensitivity to the product.

Warning

      1. It is not for intravenous, subcutaneous, or intramuscular administration.

      2. BCG vaccine is strictly given intracutaneously. A local reaction at the vaccination site is normal after a BCG vaccination. It may take the form of a nodule, which in many cases will break down and suppurate. The reaction developing at the vaccination site usually subsides within 2 to 5 months and in practically all children leaves a superficial scar of 2 to 10 mm in diameter. The nodule may persist and ulcerate. Swelling of regional lymph nodes may also be seen, and this may be regarded as a normal reaction. Keloid and lupoid reactions may occur at the site of the vaccination. Children with such reactions should not be revaccinated. Inadvertent subcutaneous injections produce abscess formations and may lead to ugly retracted scars.

      Among the major complications, suppurative lymphadenitis has been observed.

      3. Risk-benefit should be considered if it is to be used in pregnant women.

Additional information

      1. It has been administered concurrently with yellow fever vaccine without interference with the immune response to either vaccine.

      2. It may not be effective if administered during therapy with some antituberculosis agents.

      3. If acute overdosage of BCG vaccine occurs and there is reason to suspect that a generalized BCG infection may develop, isoniazid or other appropriated antituberculosis agent therapy should be initiated.

      4. Healthy neonates and infants younger than 2 months of age who have not been exposed to tuberculosis, may receive freeze-dried BCG vaccine without tuberculin skin testing.

Expiration date The expiration date is not later than 3 years from the date of the last satisfactory test for the number of culturable particles, if stored at a temperature between 2º and 8º or as stated on the label.

Packaging and storage Freeze-Dried BCG Vaccine shall be kept in tightly closed containers, preferably of Type I glass, protected from light, and stored at a temperature between 2º and 8º; avoid freezing.

Labelling Complies with the “General Information for Biological Products”, p. 177. In addition, the label on the container states (1) the description “intracutaneous use”; (2) the number of culturable particles in each single human dose; (3) the volume and nature of the reconstituting fluid; (4) that it shall not be exposed to strong daylight either before or after reconstitution; (5) that after reconstitution it should be used immediately after preparation and any portion not used within 2 hours should be discarded.

Identification

1. When examined microscopically in stainedsmears, the bacilli exhibit the characteristics of an authentic strain of the bacillus of Calmette and Guérin.

2. Colonies grown on a suitable solid culture medium have a characteristic appearance.

Virulent mycobacteria Inject subcutaneously or intramuscularly into each of six guinea-pigs, each weighing 250 to 400 g and having received no treatment likely to interfere with the test, a quantity of the vaccine equivalent to at least 50 human doses. Observe the animals for at least 6 weeks. At the end of this period, kill the guinea-pigs and examine by autopsy for signs of infection with tuberculosis, ignoring any minor reactions at the site of injection. Animals that die during the observation period are also examined for signs of tuberculosis. The vaccine complies with the test if none of the guinea-pigs shows signs of tuberculosis and if not more than one animal dies during the observation period. If two animals die during this period and autopsy does not reveal signs of tuberculosis, repeat the test on six other guinea-pigs. The vaccine complies with the test if not more than one animal dies during the 6 weeks following the injection and autopsy does not reveal any sign of tuberculosis.

Bacterial and fungal contamination The reconstituted vaccine complies with the “Sterility Test” (Appendix 10.1) except for the presence of mycobacteria.

Test of skin reaction (Excessive dermal reactivity) Use six healthy white or palecoloured guinea-pigs, each weighing not less than 250 g and having received no treatment likely to interfere with the test. Inject intracutaneously into each guinea-pig, according to a randomized plan, 0.1 ml of the reconstituted vaccine and of 2 tenfold serial dilutions of the vaccine and identical doses of the comparison vaccine. Observe the lesions formed at the site of the injection for 4 weeks. The vaccine complies with the test if the reaction it produces is not markedly different from that produced by the National or International Reference Preparation of Freeze-Dried BCG Vaccine.

Temperature stability Maintain samples of the freezedried vaccine at 37º for 4 weeks. Determine the number of viable units in the heated vaccine and in unheated vaccine as described below. The number of viable units in the heated vaccine is not less than 20 per cent that in unheated vaccine.

Number of culturable particles Determine the number of viable units in the reconstituted vaccine by using the method described below.

      Reconstitute the vaccine being examined and further dilute in sterile water to a concentration of 0.5 × 10^–4 mg of moist bacteria per ml. Inoculate each dilution to a suitable validated medium at a dose of 0.1 ml; incubate the cultures at 37º to 38º for 4 weeks, and count the number of appearing colonies per culture tube. Count the National or International Reference Preparation of Freeze-Dried BCG Vaccine in parallel for comparison.

      Freeze-Dried BCG Vaccine contains not less than and not more than the number of viable units stated on the label.