Many, if not most, industrially important fermentation and bioreactor operations are carried out in fed-batch mode, producing a wide variety of products. In spite of this, there is no single book that deals with fed-batch operations. This is the first book that presents all the necessary background material regarding the 'what, why and how' of optimal and sub-optimal fed-batch operations. Numerous examples are provided to illustrate the application of optimal fed-batch cultures. This unique book, by world experts with decades of research and industrial experience, is a must for researchers and industrial practitioners of fed-batch processes (modeling, control and optimization) in biotechnology, fermentation, food, pharmaceuticals and waste treatment industries.

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.

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.

This book is the culmination of three decades of accumulated experience in teaching biotechnology professionals. It distills the fundamental principles and essential knowledge of cell culture processes from across many different disciplines and presents them in a series of easy-to-follow, comprehensive chapters. Practicality, including technological advances and best practices, is emphasized. This second edition consists of major updates to all relevant topics contained within this work. The previous edition has been successfully used in training courses on cell culture bioprocessing over the past seven years. The format of the book is well-suited to fast-paced learning, such as is found in the intensive short course, since the key take-home messages are prominently highlighted in panels. The book is also well-suited to act as a reference guide for experienced industrial practitioners of mammalian cell cultivation for the production of biologics.

This volume covers a wide spectrum of techniques and approaches that are used in the upstream and downstream processing for recombinant glycoprotein production. Chapters guide the reader through state-of-art of therapeutic recombinant glycoproteins, explores the patent literature, expression systems used for glycoproteins production, methods employed in the downstream processing of different glycoproteins, and information about analytical tools and formulation strategies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Recombinant Glycoprotein Production: Methods and Protocols aims to ensure successful results in the further study of this vital field

This book provides essential molecular techniques and protocols for analyzing microbes that are useful for developing novel bio-chemicals, such as medicines, biofuels, and plant protection substances. The topics and techniques covered include: microbial diversity and composition; microorganisms in the food industry; mass cultivation of sebacinales; host-microbe interaction; targeted gene disruption; function-based metagenomics to reveal the rhizosphere microbiome; mycotoxin biosynthetic pathways; legume-rhizobium symbioses; multidrug transporters of yeast; drug-resistant bacteria; the fungal endophyte piriformospora indica; medicinal plants; arbuscular mycorrhizal fungi; biosurfactants in microbial enhanced oil recovery; and biocontrol of the soybean cyst nematode with root endophytic fungi; as well as microbe-mediated drought tolerance in plants.

This book is the lasting product, a resource of up-to-date information in the scientific literature for the field of animal cell technology, as it was presented during a pleasant and stimulating meeting in Tylösand, Sweden, in June 2001. The title of the meeting, From Target to Market, indicates the usefulness of Animal Cell Technology during all steps in the pharmaceutical development process. Following the biotech products reaching the market, it shows an upward trend in the contribution of biotech products to total New Molecular Entity output in the nineties, which continued until 1996 when biotech represented 25% of the annual output. Since then the proportion has been decreasing. A perceived hurdle from a market perspective is that a protein per definition is biodegradable and thus requires intravenous, or for some drugs subcutaneous administration. New promising administration technologies such as pulmonary delivery were highlighted at this meeting. The emphasis on project selection prior to entry in the development phase has triggered a portfolio management using more extensive preclinical data before a development decision is taken. Animal cells have become a very important tool in the drug discovery process. The next generation of products will evolve from applications such as gene therapy, novel vaccines, cell therapy, and gene regulation. Animal cell technology has a major role to play in the post-sequence era.

“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.

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 book gives a review of penicillin production by Penicillium chrysogenum, and also deals with a number of general aspects of fungal cultivations, e.g. primary metabolism of filamentous fungi, morphology, monitoring of fungal cultivations, and bioreactor performance (more than 750 references).The first two chapters give an introduction to the area of penicillin production; with a review of the history and a survey of the present status of this industrially very important process in the first chapter. In the second chapter is given an introduction to the microorganism, i.e. its nutritional requirements, its taxonomy, and an overview of different strain development programmes.Chapter 3 gives an introduction to the concept of Physiological Engineering. This is followed by a review of various monitoring techniques and different theoretical techniques for analysis of cultivation processes, e.g. mathematic modeling, metabolic flux analysis, and metabolic control analysis.Chapter 4 and 5 give a review of the metabolism, with the primary metabolism being the topic of Chapter 4 and the secondary metabolism, i.e. penicillin biosynthesis, being the topic of Chapter 5. The review of the penicillin biosynthetic pathway is followed by a description of a number of results obtained using metabolic flux and metabolic control analysis.Chapter 6 is devoted to the morphology of the fungus, and it gives a detailed description of the growth mechanisms of filamentous fungi.Chapter 7 deals with the bioreactor performance during fungal cultivations, i.e. medium rheology, gas-liquid mass transfer, and mixing.Finally is the fed-batch process applied for penicillin production described in Chapter 8. It gives an overview of the most important factors influencing penicillin production.