An interdisciplinary approach, integrating biochemistry, biology, genetics, and engineering for the effective production of protein pharmaceuticals. The volume offers a biological perspective of large-scale animal cell culture and examines diverse processing strategies, process management, regulator
Animal cell culture is an important laboratory technique in the biological and medical sciences. It has become an essential tool for the study of most biochemical and physiological processes and the use of large-scale animal cell culture has become increasingly important to the commercial production of specific compounds for the pharmaceutical industry. This book describes the basic requirements for establishing and maintaining cell cultures both in the laboratory and in large-scale operations. Minimal background knowledge of the subject is assumed and therefore it will be a readable introduction to animal cell culture for undergraduates, graduates and experienced researchers. Reflecting the latest developments and trends in the field, the new topics include the latest theory of the biological clock of cell lines, the development of improved serum-free media formulations, the increased understanding of the importance and control of protein glycosylation, and the humanization of antibodies for therapeutic use.
The proceedings of the 10th meeting of the European Society for Animal Cell Technology, representing an up to date survey of recent research into the production of biologicals from animal cells. The meeting dealt specifically with the commercial production of biologicals.
The editors have enlisted a broad range of experts, including microbial ecologists, physiologists, geneticists, biochemists, molecular biologists, and biochemical engineers, who offer practical experience not found in texts and journals. This comprehensive perspective makes MIMB a valuable "how to" resource, the structure of which resembles the sequence of operation involved in the development of a commercial biological process and product.
The submersed cultivation of organisms in sterile containments or fermenters has become the standard manufacturing procedure, and will remain the gold standard for some time to come. This book thus addresses submersed cell culture and fermentation and its importance for the manufacturing industry. It goes beyond expression systems and integrally investigates all those factors relevant for manufacturing using suspension cultures. In so doing, the contributions cover all industrial cultivation methods in a comprehensive and comparative manner, with most of the authors coming from the industry itself. Depending on the maturity of the technology, the chapters address in turn the expression system, basic process design, key factors affecting process economics, plant and bioreactor design, and regulatory aspects.
The completion of the Human Genome Project and the rapid progress in cell bi- ogy and biochemical engineering, are major forces driving the steady increase of approved biotech products, especially biopharmaceuticals, in the market. Today mammalian cell products (“products from cells”), primarily monoclonals, cytokines, recombinant glycoproteins, and, increasingly, vaccines, dominate the biopharmaceutical industry. Moreover, a small number of products consisting of in vitro cultivated cells (“cells as product”) for regenerative medicine have also been introduced in the market. Their efficient production requires comprehensive knowledge of biological as well as biochemical mammalian cell culture fundamentals (e.g., cell characteristics and metabolism, cell line establishment, culture medium optimization) and related engineering principles (e.g., bioreactor design, process scale-up and optimization). In addition, new developments focusing on cell line development, animal-free c- ture media, disposables and the implications of changing processes (multi-purpo- facilities) have to be taken into account. While a number of excellent books treating the basic methods and applications of mammalian cell culture technology have been published, only little attention has been afforded to their engineering aspects. The aim of this book is to make a contribution to closing this gap; it particularly focuses on the interactions between biological and biochemical and engineering principles in processes derived from cell cultures. It is not intended to give a c- prehensive overview of the literature. This has been done extensively elsewhere.
Offers a comprehensive overview of cell culture engineering, providing insight into cell engineering, systems biology approaches and processing technology In Cell Culture Engineering: Recombinant Protein Production, editors Gyun Min Lee and Helene Faustrup Kildegaard assemble top class authors to present expert coverage of topics such as: cell line development for therapeutic protein production; development of a transient gene expression upstream platform; and CHO synthetic biology. They provide readers with everything they need to know about enhancing product and bioprocess attributes using genome-scale models of CHO metabolism; omics data and mammalian systems biotechnology; perfusion culture; and much more. This all-new, up-to-date reference covers all of the important aspects of cell culture engineering, including cell engineering, system biology approaches, and processing technology. It describes the challenges in cell line development and cell engineering, e.g. via gene editing tools like CRISPR/Cas9 and with the aim to engineer glycosylation patterns. Furthermore, it gives an overview about synthetic biology approaches applied to cell culture engineering and elaborates the use of CHO cells as common cell line for protein production. In addition, the book discusses the most important aspects of production processes, including cell culture media, batch, fed-batch, and perfusion processes as well as process analytical technology, quality by design, and scale down models. -Covers key elements of cell culture engineering applied to the production of recombinant proteins for therapeutic use -Focuses on mammalian and animal cells to help highlight synthetic and systems biology approaches to cell culture engineering, exemplified by the widely used CHO cell line -Part of the renowned "Advanced Biotechnology" book series Cell Culture Engineering: Recombinant Protein Production will appeal to biotechnologists, bioengineers, life scientists, chemical engineers, and PhD students in the life sciences.
Mammalian cell lines command an effective monopoly for the production of therapeutic proteins that require post-translational modifications. This unique advantage outweighs the costs associated with mammalian cell culture, which are far grater in terms of development time and manufacturing when compared to microbial culture. The development of cell lines has undergone several advances over the years, essentially to meet the requirement to cut the time and costs associated with using such a complex hosts as production platforms. This book provides a comprehensive guide to the methodology involved in the development of cell lines and the cell engineering approach that can be employed to enhance productivity, improve cell function, glycosylation and secretion and control apoptosis. It presents an overall picture of the current topics central to expression engineering including such topics as epigenetics and the use of technologies to overcome positional dependent inactivation, the use of promoter and enhancer sequences for expression of various transgenes, site directed engineering of defined chromosomal sites, and examination of the role of eukaryotic nucleus as the controller of expression of genes that are introduced for production of a desired product. It includes a review of selection methods for high producers and an application developed by a major biopharmaceutical industry to expedite the cell line development process. The potential of cell engineering approch to enhance cell lines through the manipulation of single genes that play important roles in key metabolic and regulatory pathways is also explored throughout.
Volumes are organized topically and provide a comprehensive discussion of developments in the respective field over the past 3-5 years. The series also discusses new discoveries and applications. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthesis and purification. In general, special volumes are edited by well-known guest editors. The series editor and publisher will however always be pleased to receive suggestions and supplementary information. Manuscripts are accepted in English.
Since the introduction of recombinant human growth hormone and insulin a quarter century ago, protein therapeutics has greatly broadened the ho- zon of health care. Many patients suffering with life-threatening diseases or chronic dysfunctions, which were medically untreatable not long ago, can attest to the wonder these drugs have achieved. Although the ?rst generation of p- tein therapeutics was produced in recombinant Escherichia coli, most recent products use mammalian cells as production hosts. Not long after the ?rst p- duction of recombinant proteins in E. coli, it was realized that the complex tasks of most post-translational modi?cations on proteins could only be ef?ciently carried out in mammalian cells. In the 1990s, we witnessed a rapid expansion of mammalian-cell-derived protein therapeutics, chie?y antibodies. In fact, it has been nearly a decade since the market value of mammalian-cell-derived protein therapeutics surpassed that of those produced from E. coli. A common characteristic of recent antibody products is the relatively large dose required for effective therapy, demanding larger quantities for the treatment of a given disease. This, coupled with the broadening repertoire of protein drugs, has rapidly expanded the quantity needed for clinical applications. The increasing demand for protein therapeutics has not been met exclusively by construction of new manufacturing plants and increasing total volume capacity. More - portantly the productivity of cell culture processes has been driven upward by an order of magnitude in the past decade.