Upstream Processing

Matrix: The Highly Automated Multibioreactor Solution That Fits to Your Bench Space, Bioprocessing Needs, and Budget

To improve their bioprocess performance, life-science specialists need flexibility in their R&D laboratories because of constantly changing bioprocessing demands. In addition, more experiments need to be performed with more accuracy and reproducibility on less bench space than ever before — and with limited budgets. Therefore, having flexibility in the number of bioreactors that fit available bench space and budget is crucial — along with the flexibility to connect and integrate the right software, sampling tools, and analytical devices. Running multiple…

Innovative Strategies for Cell Culture Media Preparation

Although the handling and preparation of cell culture media can seem routine, a number of risks are associated with such operations. Identification and mitigation of associated risks can help ensure consistency of performance, minimize likelihood of contamination, and protect employees while enabling greater efficiencies in upstream processes. Here we describe a number of strategies for reducing risks and streamlining media-related workflows. Simplifying Handling of Cell Culture Powders Media preparation typically is quite labor intensive and poses risks related to containment…

eBook: Addressing Production Complexities — Strategies for Working with Difficult and Susceptible Proteins

All proteins are complex — but some are more complex than others, particularly when it comes to recombinant protein expression and production in commercial quantities. What works in a research laboratory to make a milligram of pure protein for study won’t necessarily work on a manufacturing floor to make kilogram batches for drug-product formulation. An increasing number of technological options are available, however, from a simple switch in expression host or adding folding steps in downstream processing to special genetic…

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

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 —…

The Critical Role of Media in Intensified Upstream Processes

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…

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

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.…

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

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…

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

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…

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

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…

A Challenging Future for Fetal Bovine Serum

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…