[Title 21 CFR 620.40]
[Code of Federal Regulations (annual edition) - April 1, 1996 Edition]
[Title 21 - FOOD AND DRUGS]
[Chapter I - FOOD AND DRUG ADMINISTRATION,]
[Subchapter F - BIOLOGICS]
[Part 620 - ADDITIONAL STANDARDS FOR BACTERIAL PRODUCTS]
[Subpart E - Bacillus of Calmette and Guerin (BCG) Vaccine]
[Sec. 620.40 - BCG Vaccine.]
[From the U.S. Government Publishing Office]




  21
  FOOD AND DRUGS
  7
  1996-04-01
  1996-04-01
  false
  
  620.40
  Sec. 620.40
  
    FOOD AND DRUGS
    FOOD AND DRUG ADMINISTRATION,
    BIOLOGICS
    ADDITIONAL STANDARDS FOR BACTERIAL PRODUCTS
    Bacillus of Calmette and Guerin (BCG) Vaccine
  


Sec. 620.40  BCG Vaccine.

    (a) Proper name and definition. The proper name of this product is 
BCG Vaccine. The product is defined as a freeze-dried preparation 
containing viable bacteria of the Bacillus of Calmette and Guerin, which 
is an attenuated strain of Mycobacterium bovis.
    (b) Criteria for an acceptable strain. The source of the BCG strain 
used in the manufacture of any lot of the final product must be 
identified by complete historical records.
    (1) Seed lot system. The BCG strain must be maintained in the form 
of a primary seed lot that is to be the basic material from which all 
secondary seed lots are prepared. Production of BCG Vaccine may be from 
either primary or secondary seed lots. Each seed lot must be stored in 
either a freeze-dried state at -20 deg. C or colder, or in a frozen 
state at -70 deg. C or colder.
    (2) Freedom from virulence. The BCG strain is demonstrated to be 
incapable of producing progressive tuberculosis in guinea pigs tested as 
prescribed in Sec. 620.45, except that no fewer than 48 guinea pigs must 
be used to test the primary seed lot and no fewer than 12 guinea pigs 
must be used to test each secondary seed lot. At least two-thirds of the 
animals must survive the observation period of no less than 6 months.
    (3) Induction of tuberculin sensitivity in guinea pigs. Each of at 
least 10 guinea pigs is to be injected with 1 human dose of BCG Vaccine 
and, within 4 to 6 weeks after vaccination, skin tested with tuberculin. 
At least 80 percent of the guinea pigs tested must develop tuberculin 
sensitivity, as prescribed in Sec. 620.44(b)(3)(ii).
    (4) Clinical information. Clinical data must establish that the BCG 
strain is safe and induces tuberculin sensitivity. After having passed 
all laboratory tests prescribed for BCG Vaccine, each primary and 
secondary seed lot of vaccine must be tested for its ability to induce 
sensitivity in tuberculin-negative persons. Only those persons tested by 
injection of 5 U.S. Tuberculin Units, Purified Protein Derivative, by 
the Mantoux technique and found negative in this test are to be selected 
for clinical trials. At least 100 tuberculin-negative persons must be 
included in the test of the primary seed lot, and at least 20 
tuberculin-negative persons must be included in the test of each 
secondary seed lot. Within 6 to 8 weeks after BCG vaccination, the 
vaccinees must be tested for tuberculin reactivity by injecting not more 
than 10 U.S. Tuberculin Units, Purified Protein Derivative, by the 
Mantoux technique. The test is considered satisfactory if a least 90 
percent of those persons from each group develop tuberculin reactivity 
as indicated by an induration reaction of at least 5 millimeters in 
diameter.