[Title 21 CFR 630.10]
[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 630 - ADDITIONAL STANDARDS FOR VIRAL VACCINES]
[Subpart B - Poliovirus Vaccine Live Oral Trivalent]
[Sec. 630.10 - Poliovirus Vaccine Live Oral Trivalent.]
[From the U.S. Government Publishing Office]




  21
  FOOD AND DRUGS
  7
  1996-04-01
  1996-04-01
  false
  
  630.10
  Sec. 630.10
  
    FOOD AND DRUGS
    FOOD AND DRUG ADMINISTRATION,
    BIOLOGICS
    ADDITIONAL STANDARDS FOR VIRAL VACCINES
    Poliovirus Vaccine Live Oral Trivalent
  


Sec. 630.10  Poliovirus Vaccine Live Oral Trivalent.

    (a) Proper name and definition. The proper name of this product 
shall be Poliovirus Vaccine Live Oral Trivalent. The vaccine shall be a 
preparation containing the three types of live, attenuated polioviruses 
grown in monkey kidney cell cultures, or in a cell line found by the 
Director, Center for Biologics Evaluation and Research, to meet the 
requirements of Sec. 610.18(c) of this chapter. The vaccine shall be 
prepared in a form suitable for oral administration.
    (b) Criteria for acceptable strains. (1) The Sabin strains of 
attenuated poliovirus, Type 1 (LS-c, 2ab/KP2), Type 2 (P712, Ch, 
2ab/KP2), and Type 3 (Leon 12a1b/KP3), or derivatives 
from them, may be used in the manufacture of vaccine.
    (2)(i) Other poliovirus strains may be used in the manufacture of 
Poliovirus Vaccine Live Oral Trivalent provided that they are identified 
by historical records including:
    (A) Origin,

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    (B) Techniques of attenuation,
    (C) Antigenic properties,
    (D) Neurovirulence for monkeys,
    (E) Pathogenicity for tissue cultures of various cell types, and
    (F) Established virus markers, including rct/40, and d.
    (ii) The data shall be submitted to the Director, Center for 
Biologics Evaluation and Research, along with other data that establish:
    (A) That each such strain is at least as safe as the Sabin strain of 
the corresponding type,
    (B) That each such strain demonstrates results comparable to the 
Sabin srain when inoculated into monkeys by the intrathalamic and 
intramuscular routes, and
    (C) That each such strain has been used to produce vaccines meeting 
the safety and potency requirements of Secs. 630.11, 630.15, 630.16 or 
630.17, and 630.18.
    (3) The Director, Center for Biologics Evaluation and Research, may 
prohibit the use of a specified strain whenever the Director finds that 
it is practicable to use another strain of the same type that will 
produce a vaccine of greater safety and of at least equivalent potency.
    (4) If vaccine lots have been produced directly from strain 
materials (e.g., Sabin Original, Sabin Original Merck, or Sabin Original 
Rederived), the strain material is not required to be tested in 
accordance with the provisions of Sec. 630.10(c).
    (c) Criteria for qualification of the seed virus. (1) Each seed 
virus used in vaccine manufacture shall be prepared from an acceptable 
strain in monkey kidney cell cultures, derived from animals which have 
met all of the requirements of Sec. 630.12(a), or in a cell culture of a 
type determined to be suitable by the Director, Center for Biologics 
Evaluation and Research. The seed virus used in vaccine manufactures 
shall be demonstrated to be free of extraneous microbial agents except 
for unavoidable bacteriophage.
    (2) Seed virus used for the manufacture of oral poliovirus vaccine 
shall meet the requirements of Secs. 630.13, 630.16 or 630.17, and 
630.18. In addition, the neurovirulence of each of the first five 
consecutive monovalent virus pools prepared from the seed virus shall 
meet the neurovirulence requirements prescribed in Secs. 630.16(b)(2) or 
630.17 (b)(3).
    (3) A new seed virus may be used for production provided data are 
submitted in the form of a product license a supplement that show the 
new seed virus and each of the first five consecutive monovalent virus 
pools prepared from it meet the safety requirements of Secs. 630.13 and 
630.16 or 630.17 and 630.18 and approval for the use of the seed virus 
is received in writing from the Director, Center for Biologics 
Evaluation and Research.
    (4) Seed virus in vaccine manufacture shall be prepared in a seed 
lot system from a master virus seed lot at a passage level consistent 
with Sec. 630.13(a).
    (5) For monovalent virus pools tested in accordance with 
Sec. 630.16(b), the use of the seed virus may continue provided that the 
frequency of monovalent virus pools produced with it which fail to meet 
the criteria of neurovirulence for monkeys prescribed in 
Sec. 630.16(b)(2) is not greater than predicted on the basis of 
comparison with the corresponding reference preparation. If the 
frequency of monovalent virus pools produced with the same seed virus 
which fail to meet the criteria of neurovirulence for monkeys prescribed 
in Secs. 630.16(b)(2) is greater than the predicted 1 percent on the 
basis of the 99-percent fiduciary one-sided upper limit, that seed virus 
shall be disqualified for further use in vaccine production.
    (6) For monovalent virus pools tested in accordance with 
Sec. 630.17, subsequent and identical neurovirulence tests of the seed 
virus shall be performed in monkeys whenever there is evidence of a 
significant increase in the neurovirulence of the seed virus, upon 
introduction of a new production seed lot, and as often as is necessary 
to otherwise establish, to the satisfaction of the Director, Center for 
Biologics Evaluation and Research, that the seed virus for vaccine 
manufacture has maintained its neurovirulence properties as set forth in 
Sec. 630.17 (b)(3).

[56 FR 21432, May 8, 1991, as amended at 59 FR 49351, Sept. 28, 1994]

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