[Title 21 CFR 630.32]
[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 D - Measles Virus Vaccine Live]
[Sec. 630.32 - Manufacture of live, attenuated Measles Virus Vaccine.]
[From the U.S. Government Publishing Office]




  21
  FOOD AND DRUGS
  7
  1996-04-01
  1996-04-01
  false
  
  630.32
  Sec. 630.32
  
    FOOD AND DRUGS
    FOOD AND DRUG ADMINISTRATION,
    BIOLOGICS
    ADDITIONAL STANDARDS FOR VIRAL VACCINES
    Measles Virus Vaccine Live
  


Sec. 630.32   Manufacture of live, attenuated Measles Virus Vaccine.

    (a) Virus cultures. Virus shall be propagated in chick embryo tissue 
cultures.
    (b) Virus propagated in chick embryo tissue cultures. Embryonated 
chicken eggs used as the source of chick embryo tissue for the 
propagation of measles virus shall be derived from flocks certified to 
be free of Salmonella pullorum, avian tuberculosis, fowl pox, Rous 
sarcoma, avian leucosis, reticuloendotheliosis virus, and other 
adventitious agents pathogenic for chickens. If eggs are procured from 
flocks that are not so certified, tests shall be performed to 
demonstrate freedom of the vaccine from such agents. (See 
Sec. 630.35(a)(8) for test for avian leucosis.)
    (c) [Reserved]
    (d) Passage of virus strain in vaccine manufacture. Virus in the 
final vaccine shall represent no more than ten tissue culture passages 
beyond the passage used to perform the clinical trials (Sec. 630.30(b)) 
which qualified the manufacturer's vaccine strain for license.

[[Page 103]]

    (e) Tissue culture preparation. Only primary cell tissue cultures 
shall be used in the manufacture of Measles Virus Vaccine. Continuous 
cell lines shall not be introduced or propagated in Measles Virus 
Vaccine manufacturing areas.
    (f) Control vessels. (1) From the tissue used for the preparation of 
tissue cultures for growing attenuated measles virus, an amount of 
processed cell suspension equivalent to that used to prepare 500 ml. of 
tissue culture shall be used to prepare uninfected tissue control 
materials. This material shall be distributed in control vessels and 
observed microscopically for a period of no less than 14 days beyond the 
time of inoculation of the production vessels with measles virus; but if 
the production vessels are held for use in vaccine manufacture for more 
than 14 days, the control vessels shall be held and observed for the 
additional period. At the end of the observation period or at the time 
of virus harvest, whichever is later, fluids from the control cultures 
shall be tested for the presence of adventitious agents as follows:

    Samples of fluid from each control vessel shall be collected at the 
same time as fluid is harvested from the corresponding production 
vessels. If multiple virus harvests are made from the same cell 
suspension, the control samples for each harvest shall be frozen and 
stored at -60 deg. C. until the last viral harvest for that cell 
suspension is completed. The fluid from all the control samples from 
that suspension shall be pooled in proportionate amounts and at least 
five ml. inoculated into human and simian cell tissue culture systems 
and in the tissue culture system used for virus production. The cultures 
shall be observed for the presence of changes attributable to growth of 
adventitious viral agents including hemadsorption viral agents.

    (2) The cell sheets of one quarter to one third of the control 
vessels shall be examined at the end of the observation period (14 days 
or longer) for the presence of hemadsorption viruses by the addition of 
guinea pig red blood cells. If the chick embryo cultures were not 
derived from a certified source (paragraph (b) of this section), the 
remaining tissue culture controls may be used to test for avian leucosis 
virus using either Rubin's procedure for detecting Resistance Inducing 
Factor (RIF) or a method of equivalent effectiveness.
    (3) The test is satisfactory only if there is no evidence of 
adventitious viral agents and if at least 80 percent of the control 
vessels are available for observation at the end of the observation 
period (14 days or longer).
    (g) Test samples. Samples of virus harvests or pools for testing by 
inoculation into animals, into tissue culture systems, into embryonated 
hens' eggs, and into bacteriological media, shall be withdrawn 
immediately after harvesting or pooling but prior to freezing except 
that samples of test materials frozen immediately after harvesting or 
pooling and maintained at -60 deg. C. or below, may be tested upon 
thawing, provided no more than two freeze-thaw cycles are employed. The 
required tests shall be initiated without delay after thawing.

[38 FR 32068, Nov. 20, 1973, as amended at 40 FR 11719, Mar. 13, 1975; 
47 FR 24699, June 8, 1982]