Large-scale Mammalian Cell Culture Research Articles

ESACT meeting overview: Back to the future

This joint meeting of the European Society of Animal Cell Technology (ESACT) and the Japanese Association of Animal Cell Technology (JAACT), addressed the scientific and engineering principles underpinning the process of producing therapeutic proteins in animal cells. ESACT has held meetings on this topic on a regular basis since 1976. Originally the focus was on the use of large scale mammalian cell culture for the production of vaccines but over the years additional products such as monoclonal antibodies and recombinant therapeutic proteins have become increasingly important. Prior to the conference the executive committee debated the issue of how the society should progress and look to develop new growth areas. As a result of these discussions a mission statement and set of aims was produced. At the General Assembly of the Society held during the conference the ESACT members voted to incorporate these amendments into the constitution of the society. These proposals (listed in Table 1) are relevant to the theme of this meeting "Developments towards the 21 st century" and to the topic addressed by Professor Charles Cooney in his opening address. Cooney posed the question "Are we ready for the 21 st century?" and reviewed past developments in the field of animal cell technology. His conclusion was that much has been achieved: many products from animal cells have been taken to the marketplace and are now used to treat human disease. He estimated that animal cell products generated worldwide sales of around US $ 3 billion per annum. The development time for these products is around ten years, however, so if we wish to consider the products which will be available in the 21st century we must consider those that are currently being developed. We can't afford to be complacent about past success because this long lead-in time means that the future is very near. Past successes which were identified included the development of the technology for growing cells on Table 1. The revised mission statement for the European Society for Animal Cell Technology

Large-scale mammalian cell culture.

Over the past year, progress has been made toward a better understanding of the physiological and biochemical responses of cell cultures to various environmental changes. Much of the theoretical and experimental work that has been reported will help improve expression in mammalian cell culture, which is one of the key steps in biopharmaceutical manufacturing.

Large‐Scale, High‐density freezing of hybridomas and its application to high‐density culture

Large-scale, high-density freezing of hybridomas was studied to apply frozen cells to start high-density culture. We showed here that hybridomas can be frozen at 1.5 x 10(8) cells/mL, without decrement in viability and proliferating activity. Blood transporting bags were used for large-scale freezing to store 25 mL of cell suspension with a cell density, 1.5 x 10(8)/mL. The number of cells stored in a bag (3.0 x 10(9) cells) was enough to start a high-density culture at a 10 times higher cell density (6.0 x 10(6) cells/mL) than normal inoculation, and the cells proliferated to 10(7) cells/mL within 2 days. These results indicate that the large-scale freezing method is useful for large-scale culture of mammalian cells.

Large-scale mammalian cell culture: methods, applications and products.

Animal cell cultures are used to generate products of enormous biotechnological value. These systems rely on conventional manufacturing techniques using organisms that are the result of either cell fusions or genetic engineering. A wealth of new techniques has allowed improvements and developments to be made in culture medium composition, cell modification, and bioreactor design and operation. This progress is expected to be commercially exploited as new products reach the market place.

Safety aspects in the quality control of recombinant products from mammalian cell culture

The recent approval of the recombinant DNA-derived biological, human tissue-type plasminogen activator (rt-PA), obtained from large scale mammalian cell culture, addressed a number of issues concerning the safety of recombinant products. The assurance of the safety of such highly complex proteins requires that the following topics be investigated: the characterisation of the recombinant production organism; control of large scale cell culture production conditions; design of the purification process and consistency of manufacture; the purity, safety, and stability testing of the final product; and clinical studies. Each of the topics described above is discussed with respect to those key quality control issues that ensure the safety of the product. The use of analytical techniques such as peptide mapping and multiantigen ELISA assays to guarantee both the genetic stability and the purity of the final product is also discussed.

Large‐scale mammalian cell culture. Edited by J. Feder and W. R. Tolbert, Academic Press, Orlando, Florida, 1985. pp. ix + 159, price £15.50, $18.50. ISBN 0‐12‐250431‐3

Journal of Chemical Technology & BiotechnologyVolume 42, Issue 3 p. 242-243 Book Review Large-scale mammalian cell culture. Edited by J. Feder and W. R. Tolbert, Academic Press, Orlando, Florida, 1985. pp. ix + 159, price £15.50, $18.50. ISBN 0-12-250431-3 M. Kearns, M. KearnsSearch for more papers by this author M. Kearns, M. KearnsSearch for more papers by this author First published: 1988 https://doi.org/10.1002/jctb.280420310AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume42, Issue31988Pages 242-243 RelatedInformation

Large-scale culture of hybridoma and mammalian cells in fluidized bed bioreactors.

Annals of the New York Academy of SciencesVolume 506, Issue 1 p. 129-146 Large-Scale Culture of Hybridoma and Mammalian Cells in Fluidized Bed Bioreactors ROBERT C. DEAN JR., ROBERT C. DEAN JR. Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorSABHASH B. KARKARE, SABHASH B. KARKARE Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorNITYA G. RAY, NITYA G. RAY Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorPETER W. RUNSTADLER JR., PETER W. RUNSTADLER JR. Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorK. VENKATASUBRAMANIAN, K. VENKATASUBRAMANIAN Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854 Also with: H. J. Heinz Company, World Headquarters, Post Office Box 57, Pittsburgh, Pennsylvania 15230.Search for more papers by this author ROBERT C. DEAN JR., ROBERT C. DEAN JR. Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorSABHASH B. KARKARE, SABHASH B. KARKARE Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorNITYA G. RAY, NITYA G. RAY Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorPETER W. RUNSTADLER JR., PETER W. RUNSTADLER JR. Verax Corporation Lebanon, New Hampshire 03766Search for more papers by this authorK. VENKATASUBRAMANIAN, K. VENKATASUBRAMANIAN Department of Chemical and Biochemical Engineering Rutgers University Piscataway, New Jersey 08854 Also with: H. J. Heinz Company, World Headquarters, Post Office Box 57, Pittsburgh, Pennsylvania 15230.Search for more papers by this author First published: November 1987 https://doi.org/10.1111/j.1749-6632.1987.tb23815.xCitations: 26 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume506, Issue1Biochemical Engineering VNovember 1987Pages 129-146 RelatedInformation

Effects of dissolved oxygen concentration on hybridoma growth and metabolism in continuous culture.

Oxygen transport is a major limitation in large-scale mammalian cell culture. The effects of the dissolved oxygen concentration (DO; from 0.1 to 100% saturation with air) on Sp2/0-derived mouse hybridomas were investigated using continuous culture. The steady-state concentration of viable cells increased with decreasing DO until a critical dissolved oxygen concentration of 0.5% of air saturation was reached. The cell concentration declined at lower DO because of incomplete glutamine oxidation, and the specific lactate production from glucose increased to offset the reduced energy production from glutamine. Cell viability increased as the DO was decreased; the viability continued to increase even when the DO was reduced below 0.5%. The specific oxygen uptake rate was essentially constant for DO greater than or equal to 10% of air saturation and then decreased with decreasing DO. The P/O ratio (ATP molecules produced per O atom consumed) appears to change from 2 to 3 between 10 and 0.5% DO. The specific ATP production rate calculated using this assumption decreases only slightly with decreasing DO. The optimum DO of 50% for antibody production is different than the optimum (approximately 0.5% DO) for cell growth.

Mammalian cell culture: technology and physiology.

During the last decade phenomenal advances have taken place in large-scale mammalian cell culture both for microcarriers and suspension methods. The cost of serum and product quality require that such systems be examined in terms of both their physical and chemical parameters. Data are presented as to the method used to more than double the final harvest cell density of 100-liter batch culture reactors by simple temperature measurements and 12-liter reactors by increasing the oxygen potential of the liquid. The results are interpreted in terms of physical transport phenomena of momentum, heat and mass via the theoretical relationships of Navier -Stokes, Fourier and Fick respectively. In addition, data are presented of 3-, 12-, and 100 liter reactors that the spent cell growth media were analyzed for ten different chemistries. The Monod cell growth curve was used to interpret the results. The cost savings and product quality improvements can be enormous by approaching both the technology and physiology of mammalian cell culture from the vantage points of chemistry, thermodynamics and transport phenomena.

Large‐scale mammalian cell culture: Design and use of an economical batch suspension system

Large-scale mammalian cell culture in the absence of antibiotics requires stringent conditions of sterility for all vessels, procedure, and systems used. Application of existing fermentation technology suffers from the differences between mammalian and bacterial cultures. Relatively simple and inexpensive 100-L vessels have been designed specifically for medium storage and antibiotic-free mammalian cell culture. These vessels are portable and sterilized in a 2 x 3 x 5 ft conventional or VACUMATIC autoclave. They consist of 30-gal 316 stainless-steel sanitary process drums whose heads have been modified to meet the rapid pressure changes that occur during autoclaving. The vessels incorporate systems for aseptic introduction and removal of both liquids and gases required for inoculation, growth, and harvesting of cell suspensions. A two-disk vibromixer is used for agitation with inoculation at a laminar flow hood and incubation in a warm room. These vessels have been used for culture of one rat and eight human tumor lines for over 2 x 10(5) L of suspension.

Production of Milligram Quantities of H-2K and Thy-1 Alloantigens by Large-Scale Mammalian Cell Culture

SummaryA system for the production of milligram quantities of cell-surface alloanti-gens is presented. This system consists of 70- and 200-liter mammalian cell culture vessels capable of growing murine T-cell lines in suspension culture. The two cell lines examined exhibited superior growth properties in these vessels than in small spinner flasks. Expression of H-2Kk and Thy-1 alloantigens were higher on these cell lines than normal thymocytes. Approximately 3 μmole of Thy-1.1 and 500 nmole of H-2Kk antigens were produced in an 8-day period. The potential of the large-scale mammalian cell culture approach is briefly discussed.