An overview of animal cell substrates for biological products
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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Cited by (22)
Universal real-time PCR assay for quantitation and size evaluation of residual cell DNA in human viral vaccines
2016, BiologicalsCitation Excerpt :The manufacturing capability for viral vaccines produced in conventional/classical cell substrates such as embryonated hen eggs, primary or diploid cell lines, has now reached its capacity limit [1,2].
Size analysis of residual host cell DNA in cell culture-produced vaccines by capillary gel electrophoresis
2013, BiologicalsCitation Excerpt :In recent years, new eukaryotic cell culture platforms (e.g. insect cells, canine cells) have become increasingly attractive to manufacturers of vaccines and other biologics [1–7].
Evaluation of tumorigenic potential of high yielding cloned MDCK cells for live-attenuated influenza vaccine using in vitro growth characteristics, metastatic gene expression and in vivo nude mice model
2012, BiologicalsCitation Excerpt :For various reasons, in contrast to the vast body of information published for virus and/or virus antigen characterization, research efforts in characterizing vaccine production substrates have made much slower progress for years. It is encouraging to witness a significant increase in both interest and demand for better understanding of biological properties of human vaccine production substrates in recent years [28]. The threat posed by pandemic influenza and other emerging infectious diseases has further fueled the need to characterize novel vaccine production substrates.
Live attenuated rabies virus co-infected with street rabies virus protects animals against rabies
2011, VaccineCitation Excerpt :From the time it was developed in the 1880s to the 1940s, the basic idea and preparation of Pasteur rabies vaccine did not change significantly. With the maturation of cell culture techniques in the 1950s and 1960s [8,9], NTVs were gradually replaced by cell culture-derived rabies vaccines [10], but no major paradigm shifts in rabies vaccine development have occurred since then. In this study, we report the development of a highly attenuated RV ERAg3m, in which the matrix protein (M) gene has been switched with that of the glycoprotein (G) gene in the Evelyn–Rokitnicki–Abelseth (ERA) strain [11], and a mutation from arginine to glutamic acid in the G gene was introduced at amino acid residue 333.
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