Upstream Processing

Comparative Study of Single-Use and Reusable Fermentors: Production of Recombinant Proteins Through Bacterial Fermentation

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Single-use bioreactors have become widely accepted and well established for cell culture applications in the biopharmaceutical industry for over a decade (1). Abbott Diagnostics has moved into this technology already for commercial production of some biologic molecules. However, single-use systems (SUSs) are rarely available for microbial applications, mostly because of the technical challenge in designing cost-effective SUSs that can meet high oxygen transfer needs and remove excessive heat generated during fermentation. Thus, an important part of our biologics manufacturing —…

October 28, 2019

The Critical Role of Media in Intensified Upstream Processes

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As the need for novel therapeutics increases, so does pressure on the biopharmaceutical industry to improve productivity, accelerate development, increase, and reduce costs — all while ensuring drug product quality. Upstream intensification strategies such as perfusion culture can address those challenges and achieve higher protein titers that can translate into higher throughput, improved flexibility, and compressed timelines. Successful implementation of perfusion culture or the transition to perfusion from fed-batch culture requires a different and strategic approach to media selection, not…

October 28, 2019

Production of Transient Lentiviral Vectors in HEK 293T Cells: Cultivation on Fibra-Cel Disks in a Single-Use, Packed-Bed, Stirred-Tank Bioreactor

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Although demand for lentiviral vectors (LVs) for cell and gene therapy is increasing, the standard two-dimensional culture systems used to produce LVs present significant disadvantages. Current bottlenecks in LV production are caused mainly by such disadvantages. Switching to use of bioreactors can eliminate those problems because bioreactors offer the benefits of process automation, tight regulation of production conditions, and reduced labor input. The study reported herein was carried out by the group of David Parsons at the University of Adelaide.…

October 23, 2019

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

Advances and Challenges in Vaccine Development and Manufacture

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Scientists have made significant breakthroughs in bioprocess and analytical technologies for supporting vaccine development. Such technologies have helped vaccine manufacturers achieve consistent product purity and quality rapidly and cost effectively. Although interest in vaccine development and manufacture continues to increase because of the rapid growth of the global vaccine market, this area of the bioprocess industry remains challenging and complex. Here we review the current constraints and complexities in the vaccine industry, specifically related to product development and manufacture. We…

September 21, 2019

A Shift of Mindset: How Single-Use Systems Influence Bioprocess Engineering and Project Execution

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In past decades, the focus in bioprocess engineering was on traditional stainless steel project management, which is highly dependent on established project schedules. Many milestones, tasks, and deliverables during basic and detailed design and execution were implemented in the same tried and tested way by engineering, suppliers, and biopharmaceutical companies. Making decisions was complicated by alignment with long lead items. With the introduction of single-use (SU) technologies, the transition in execution and optimization of project management only just has been…

June 20, 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