Upstream Processing

eBook: Bioreactor Scale-Up: From Pilot to Commercial Scale in the Modern Era

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Upstream bioproduction always has begun with laboratory systems producing limited amounts of product for test purposes, then those bioprocesses are scaled up to make more product more efficiently for larger clinical trials — and ultimately commercial distribution. With the advent of single-use technology and continuous processing, how have scale-up approaches changed in recent years, specifically at the pilot-to-production level? In this online exclusive, BPI editors review the science and technology affecting decisions made at this stage of process development, with…

September 27, 2019

Creating Novel Cell Lines By Genome Editing: Simplifying Cell-Based Assays and Improving Production of Biomolecules

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Cultured cell lines have a diverse range of applications. They are used broadly by cell biologists, clinicians, tissue engineers, biotechnology scientists, and bioengineers. The most important uses of cell culture are in the cell-based assays and production of biologically active recombinant proteins. In recent years, genome editing has been used widely to study the structure, function, and localization of endogenous proteins in cultured cells. However, applying the same genome editing techniques to cell lines also could improve the propagation of…

September 26, 2019

Streamlined Serum-Free Adaptation of CHO-DG44 Cells: Using a Novel Chemically Defined Medium

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Monoclonal antibodies (MAbs) have radically transformed the treatment of many chronic diseases, mainly in the fields of oncology and autoimmunity. The overwhelming majority of therapeutic MAbs are manufactured from recombinant Chinese hamster ovary (CHO) cell lines. The original CHO cell line was isolated in the 1950s, and since the early 1980s, it has become the workhorse of the biopharmaceutical industry. The CHO-DG44 strain was generated after several rounds of mutagenesis that deleted both copies of dihydrofolate reductase (dhfr) genes by…

September 26, 2019

A Challenging Future for Fetal Bovine Serum

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Serum and other blood-derived products have been used widely in pharmaceutical research for many years. Use of these materials has contributed to many different advances in human and veterinary health, and they continue to have an important role in drug development. Fetal bovine serum (FBS) has had a specific role in the culture of mammalian cells for over 60 years. It is proven to be a useful tool for a broad spectrum of applications because it supports a large range…

September 21, 2019

eBook: Efficient Production of Adherent Cells – The Bolt-On Bioreactor Project, Next Phase

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Some years ago, The Bolt-on Bioreactor (BoB) project was launched with an objective of bringing to the market an efficient bioreactor for culturing adherent cells. The BoB team identified four challenges that needed be addressed to succeed: volumetric productivity, process automation, containment and sterility, and process economics. BPI published findings related to those challenges and proposals of the BoB team to solve them in a four-article series in 2015. Here, the author offers an update on developments in The Bolt-on…

June 14, 2019

eBook: Expression Systems — Increasing Productivity and Reducing Costs

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Biopharmaceutical manufacturers are facing increasing pressures to improve productivity and reduce time to clinic and market. Increasing productivity begins with selecting the appropriate expression system for each protein. Current efforts to boost expression titers also are focused on implementing selection/screening technologies, engineering Chinese hamster ovary (CHO) expression systems, and accelerating timelines for the development of complex next-generation therapies. BioProcess International asked three representatives of the industry’s leading companies to comment on current expression system technologies and strategies Just fill out this…

May 28, 2019

Cell Culture Bioprocessing in Perfusion: Assessing Cell Retention Technologies

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Upstream bioprocessing in perfusion mode holds great promise for industrial production of cells and biologics. In perfusion, fresh medium is added constantly to the bioreactor, and used medium is harvested while the cells are retained in the bioreactor. As a result, the composition of the cell culture medium stays quite constant during the process. This offers several advantages. In perfusion, higher cell densities can be reached than in batch and fed-batch processes, therefore enhancing volumetric productivity. Because medium composition can…

May 1, 2019

Visible Particulate Matter in Single-Use Bags: From Measurement to Prevention

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Parenteral pharmaceuticals must be “essentially free†from visible particulate matter (1). In the production of biopharmaceuticals with single-use systems (SUS), biocompatibility requires controlling interactions between drug substances/products and SUS surfaces to ensure drug product quality and patient safety with regard to extractables/leachables and particulate matter. Any particulate matter stuck to fluid-contacting surfaces of process components could wash off and contaminate process fluids. Depending on system configuration, a final drug product could be at risk for particulate matter from SUS. Risk…

April 12, 2019

Monoclonal Antibodies: Beyond the Platform in Manufacturing

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The vast majority of monoclonal antibody (MAb) production processes are based on fed-batch Chinese hamster ovary (CHO) cell culture and protein A affinity column chromatography capture. Increasing cost-consciousness — among innovator companies as well as biosimilar makers — has many companies looking “beyond the platform†for less expensive alternatives that may provide better results. Here the BPI editors review some state-of-the-art alternatives in upstream and downstream MAb drug substance bioprocessing as well as drug-product manufacturing. The current “gold standard†platform…

March 29, 2019

A Brief History of Adherent Cell Culture: Where We Come From and Where We Should Go

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In the past 20 years, novel therapeutics have become a major segment of biopharmaceutical research and development, particularly for immune disorders and cancer. Progress in gene therapies could bring cures for once deadly and debilitating genetic disorders such as hemophilia or muscular dystrophy. Biologic drug products offer potential treatments that have not been possible with traditional (chemistry-based) approaches. But such products also are more difficult to produce cost effectively at an industrial scale because of the intricacies associated with biological…

February 14, 2019