Elsevier

Biologicals

Volume 36, Issue 6, November 2008, Pages 359-362
Biologicals

An overview of animal cell substrates for biological products

https://doi.org/10.1016/j.biologicals.2008.06.004Get rights and content

Abstract

The issue of which cells to use as substrates for the production of biological products, and especially vaccines, has been with us in one form or another ever since the development of cell cultures in the 1950s.

The major cell substrate events that occurred over the past 50 years are reviewed briefly. Although numerous conferences were held during that period, incomplete resolution of some cell substrate issues has remained. Specifically, the potential oncogenicity of cellular DNA derived from continuous cell lines, and the tests that are used to rule out the presence of adventitious agents have been recognized as areas that could benefit greatly from studies using state-of-the-art techniques.

A collaborative effort involving WHO, NIAID, and IABS resulted from consensus recommendations of a 2004 conference, and the prospects for revised guidance in the near future on the characterization and use of animal cell substrates are bright.

Section snippets

Background and introduction

The selection of an appropriate cell substrate for use in the production of biological products has been a recurring focus of attention and anxiety for at least the past 50 years. The reasons for that are not difficult to understand because the central issue has always been “Is the product manufactured in a given cell substrate going to be safe to use in humans?” In that regard, the most obvious safety issue is related to the possibility of transmitting a microbial agent such as a virus that at

Phenotypic characteristics of animal cells grown in vitro

A large number of phenotypic characteristics of animal cells have been described in the literature. Of those, three characteristics have been particularly important in the assessment of cells grown in vitro that might be considered as substrates for the production of biological products. These include: (1) life potential; (2) tumorigenic potential; and (3) chromosomal complement.

With regard to life potential, cells grown in vitro may be divided into two large general classes: those with a

Animal cell substrate classification scheme

Taking into consideration the phenotypic characteristics of cells grown in vitro described above, cells may be divided into three categories: primary cells; diploid cell lines; and continuous cell lines. Primary cells are derived directly from donor tissue and which undergo minimal, if any, subcultivations in vitro. In contrast, even though diploid cell lines and continuous cell lines also originally are derived from donor tissue, the resulting cell populations may be subcultured for extended

Decisions and developments related to animal cell substrate use in the production of biologicals

In the very early days of viral vaccine development, decision-makers in the United States were faced with the choice of using human cancer cells (HeLa) or “normal” cells as the substrate for an experimental adenovirus vaccine. Because relatively little was known about the basis of human cancer and the risks that might be involved in the use of such cells for vaccine production, “normal” cells were selected as the substrate of choice in 1954 [1]. That decision eventually led to the use of

Summary and conclusions

As one looks back over the history of animal cell substrates used for the production of biological products, it becomes quite apparent that the theoretical risks have essentially remained the same as those that were identified in 1954: transmissible agents such as viruses and cellular components such as DNA. The major difference between 1954 and the present is that our scientific knowledge and technical abilities have improved considerably. That in turn, has allowed more relevant data to be

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