Cell Substrates for Biologics Production: Factors Affecting Acceptability

  • John C. Petricciani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 118)


At the present time, the viral vaccines licensed for use in humans in the United States are produced in cells derived from a wide variety of sources. Table 1 shows the specific cell system for each vaccine and the year in which the vaccine was licensed. To some degree the cell type used for a given vaccine reflects the available technology at the time of licensure, and the then current consensus on what constituted an acceptable cell source. The classic example, of course, is poliovirus vaccine. Primary rhesus monkey kidney cultures were used initially. With the discovery of SV-40 as a rhesus agent capable of contaminating the vaccine, primary African green monkey kidney cell culture became the substrate of choice. More recently, diploid cells of human origin have been used to produce poliovirus vaccine, thus introducing an alternate acceptable cell substrate for vaccine production. Because new data have been developed at a rapid rate over the past decade in the biological sciences, and because there has been a large experience with cells from a variety of sources in vaccine production, it is of interest to examine which criteria are of major importance in assessing the acceptability of cells. The purpose of this discussion is to review those major criteria of acceptability which have been applied to cells used in biologics production up to the present time, and to critically analyze the logic and reasonableness of those criteria in the context of the general knowlege that is currently available in the biological sciences as well as the general experience with vaccines produced in a variety of cell types. The focus will be on cell lines rather than on both cell lines and primary cultures, since the use of primary cultures will be covered in depth by Dr. Parks, and I am sure that during the course of this symposium there will be many opportunities for us to discuss the issues relating to primary cell cultures.


Biologics Production Diploid Cell Primary Cell Culture Vaccine Production Cell Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hilleman, M.R. Cells, vaccines and the pursuit of precedent. Nat. Cancer Inst. Monogr.. 29:463–470. 1968.PubMedGoogle Scholar
  2. 2.
    Swim, H.E. and Parker, R.F. Culture characteristics of human fibroblasts propagated serially. Am. J. Hyg. 66: 235–243. 1957.PubMedGoogle Scholar
  3. 3.
    Tjio, J.H. and Puck, T.T. Genetics of somatic mammalian cells II. Chromosomal constitution of cells in tissue culture. J. Exp. Med. 108:259–268. 1958.PubMedCrossRefGoogle Scholar
  4. 4.
    Hayflick, L., and Moorhead, P.S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25: 585–621. 1961.CrossRefGoogle Scholar
  5. 5.
    Sabin, A. Discussion. Session V of the International Conference on Rubella Immunization. Amer. J. Dis. Child 118:378–381. 1969.Google Scholar
  6. 6.
    Minutes of the Third Meeting of the Committee on Cell Cultures. International Association of Microbiological Societies, Permanent Section on Microbiological Standardization, Pennsylvania, 18 May 1966.Google Scholar
  7. 7.
    Moorhead, P.S., Nichols, W.W., Perkins, F.T., and Hayflick, L. Standards of karyology for human diploid cells. J. of Biological Standardization. 2:95–101. 1974.CrossRefGoogle Scholar
  8. 8.
    Minutes of the Eighth Meeting of the Committee on Cell Cultures. International Association of Microbiological Societies, Permanent Section on Microbiological Standardization, Massachusetts, 4 October 1971.Google Scholar
  9. 9.
    Fogh, J., and Fogh, H. Chromosome changes in cell culture induced by mycoplasma infection. Annals of the New York Academy of Sciences, 225:311–329. 1973.CrossRefGoogle Scholar
  10. 10.
    Wallace, R.E., Vasington, P.J., Petricciani, J.C., Hopps, H.E., Lorenz, D.E., and Kadanka, Z. Development and characterization of cell lines from subhuman primates. In Vitro 8:333–341. 1973.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • John C. Petricciani
    • 1
  1. 1.Bureau of Biologics, Food and Drug AdministrationBethesdaUSA

Personalised recommendations