Upstream Processing

Quantitative Synthetic Biology for Biologics Production

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Biologics accounted for more new drug approvals than did small molecules for the first time in 2022, marking a significant shift in the pharmaceutical industry (1). Large-molecule pipelines are also moving from standard monoclonal antibodies (MAbs) to more complex and difficult-to-express molecules, which intensifies pressure on the industry to meet biomanufacturing demands. There is a pressing need for innovative Chinese hamster ovary (CHO)–based bioproduction systems to keep pace with this evolving landscape. While multiple areas of cell-line development (CLD) have…

April 20, 2023

Shear-Proof Design Space: Scaling Stirred-Tank Bioreactors for Cell Culture Processes

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Establishing a cell culture process across different scales and models of bioreactors involves maintaining constant scale-independent parameters such as pH, temperature, and dissolved oxygen (DO). However, nonlinear and scale-dependent criteria (impeller agitation and gas flow rates) are adjusted on the basis of multiple normalized engineering parameters to accommodate the geometrical and design differences among bioreactors (1–3). Normalized engineering approaches for scaling parameterization often are based on the shear generated by impeller speed and gas flow rates. Kinetic energy transmitted into…

February 9, 2023

Deciphering Nutritional Needs in Bioprocess Optimization: Targeted and Untargeted Metabolomics with Genome-Scale Modeling

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Microbiology has risen as a major part of global industry over the past three decades. Industrial microbiology, biotechnology, biopharma and now biointelligent production systems (1) embrace a wide range of manufacturing platforms and product areas involving microbes, animal cells, and plant cells — as well as whole organisms. The multibillion-dollar applications of biomanufacturing display great variety. They include microbial-based production of such valuable metabolites as amino acids, vitamins, solvents, and organic acids as well as larger products such as enzymes,…

October 20, 2022

Recombinant Protein Expression with a Baculovirus–Insect Cell System

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Proteins create cellular matrices, catalyze biochemical reactions, and form signaling pathways to respond to external stimuli. Studies of protein structure and function increase researchers’ understanding about the foundations of life. However, because most proteins are difficult to obtain commercially, it is important to establish sources that can provide researchers with plentiful supplies of proteins. In recombinant protein expression, a gene encoding a protein of interest is cloned into an expression vector (usually a plasmid) and transferred into a host cell…

October 20, 2022

Synthetic Biology for Adapting CHO Cells to Challenging Bioprocesses

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Biopharmaceuticals are produced mainly by Chinese hamster ovary (CHO) cell lines, for which advances in protein formats, bioprocesses, and bioprocess control are introducing novel challenges (1). Thus far, those challenges have been tackled either by technical innovations and media optimization or by advances in host-cell engineering (2, 3). Some technical innovations bring further challenges, such as those related to the compatibility of CHO cultures with highly automated bioprocesses and continuous high-density culture modes (4). With regard to host-cell engineering, most…

September 28, 2022

Hardware, Software, and Wetware: 20 Years of Advancements in Biopharmaceutical Production, Part 1

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The past couple of decades have witnessed significant advances in upstream bioprocess technologies and approaches. Since its establishment, BPI has been a facilitator of discussion in both print and professional conferences, as well as in webcasts and news online. To mark the 20th anniversary of the publication, we surveyed articles published over the past two decades and found hundreds that highlight significant advances in both emerging and established themes in biopharmaceutical production: • “hardware” and assets (e.g., analytical instrumentation, bioreactors,…

August 22, 2022

Pressure Vessels for Biomanufacturing: Basic Considerations for Cleaning and Process Compatibility

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Pressure vessels are enclosed containers used to contain liquids, vapors, and gases at pressures that are significantly higher or lower than the ambient pressure of their surroundings. Equipment such as bioreactors, holding tanks, mixing tanks, separators, and heat exchangers all are examples of pressure vessels. As such, they form an integral part of biopharmaceutical manufacturing. Apart from pressure containment itself, a key challenge in building pressure vessels is making them meet the high purity and cleanability requirements of bioprocessing. As…

June 21, 2022

Genome Editing for Cell-Line Development

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At BPI Europe in April 2019, Dirk Gewert (business unit leader of bioproduction at Horizon Discovery) told BioProcess Insider that Chinese hamster ovary (CHO) cell lines haven’t changed much in the 30 years since they were first used in biomanufacturing (1). Only a few companies offered commercially available, production-ready CHO cell lines for large-scale manufacturing of biotherapeutics. “In all cases,” he said, “cell lines were selected by identifying high-expressing clones and focusing on process optimization to improve expression and other…

May 24, 2022

Cell-Line Development for Expressing IgM Antibodies

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Immunoglobulin G (IgG) antibodies have been studied and applied as biopharmaceuticals for decades, and they remain dominant in the monoclonal antibody (MAb) pipeline. By contrast, immunoglobulin M (IgM) molecules are much larger and consequently more challenging for biomanufacturing and therapeutic application. Essentially, they appear as clusters of the familiar Y-shaped IgG molecules, joined at their bases in pentameric (Figure 1) or hexameric forms. That structure gives them 10 and 12 binding moieties, respectively, which translate to superior binding power (avidity)…

May 24, 2022

Plant-Based Protein Expression: Emerging Systems Bring Viable Approaches to Biopharmaceutical Manufacturing

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The application of plant-based systems to produce biopharmaceuticals for human and veterinary indications is a rapidly expanding field. Available systems range from stable transgenic root-cell culture to transient expression in whole plants. Products that have been expressed include monoclonal antibodies (MAbs) (1), subunit vaccines (2), virus-like particles (VLPs) (3), specialty enzymes (4), and structural proteins such as collagen (5). “Traditional” bioproduction platforms such as Chinese hamster ovary (CHO) cells, Escherichia coli, and Pichia pastoris have long histories of patient safety…

May 20, 2022