[Code of Federal Regulations]
[Title 9, Volume 1]
[Revised as of January 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 9CFR113.51]

[Page 617]
 
                  TITLE 9--ANIMALS AND ANIMAL PRODUCTS
 
  CHAPTER I--ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF 
                               AGRICULTURE
 
PART 113--STANDARD REQUIREMENTS--Table of Contents
 
Sec. 113.51  Requirements for primary cells used for production of biologics.

    Primary cells used to prepare biological products shall be derived 
from normal tissue of healthy animals. When prescribed in an applicable 
Standard Requirement or in the filed Outline of Production, each batch 
of primary cells used to prepare a biological product shall be tested as 
prescribed in this section. A batch of primary cells found 
unsatisfactory by any prescribed test shall not be used. A serial of 
biological product shall not be released if produced from primary cells 
that are found unsatisfactory by any prescribed test.
    (a) Final container samples of completed product or samples of the 
final pool of harvested material or samples of each subculture of cells 
used to prepare the biological product shall be shown free of mycoplasma 
as prescribed in Sec. 113.28. The sample for testing shall consist of at 
least 75 cm\2\ of actively growing cells or the equivalent in harvest 
fluids; Provided, That all sources of cells in the batch of primary 
cells are represented.
    (b) Final container samples of completed product or samples of the 
final pool of harvested material or samples of each subculture of cells 
used to prepare the biological product shall be shown free of bacteria 
and fungi as prescribed in Sec. 113.26 or Sec. 113.27 (whichever is 
applicable).
    (c) A monolayer at least 75 cm\2\ from each batch of primary cells 
or each subculture of primary cells used to prepare a biological product 
shall be shown free of extraneous agents as prescribed in this 
paragraph.
    (1) The test monolayer shall be maintained using the medium (with 
additives) and under conditions similar to those used to prepare 
biological products.
    (i) Monolayers of avian origin shall be maintained for at least 14 
days and shall be subcultured at least once during the maintenance 
period. All but the last subculture shall result in a new monolayer of 
at least 75 cm\2\. The last subculture shall meet the minimum area 
requirement specified in Secs. 113.46 and 113.47.
    (ii) Monolayers not of avian origin shall be maintained for at least 
28 days and shall be subcultured at least twice during the maintenance 
period. All but the last subculture shall result in a new monolayer of 
at least 75 cm\2\. The last subculture shall meet the minimum area 
requirement specified in Secs. 113.46 and 113.47.
    (2) Monolayers shall be examined regularly throughout the required 
maintenance period for evidence of the presence of cytopathogenic 
agents. If evidence of a cytopathogenic agent is found, the batch of 
primary cells is unsatisfactory.
    (3) At the conclusion of the required maintenance period, monolayers 
shall be tested for:
    (i) Cytopathogenic and/or hemadsorbing agents as prescribed in 
Sec. 113.46;
    (ii) Extraneous viruses by the fluorescent antibody technique as 
prescribed in Sec. 113.47.

[50 FR 442, Jan. 4, 1985, as amended at 60 FR 24549, May 9, 1995]