2022

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

Advanced Liquid Transfer with Single-Use Systems

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Most biopharmaceuticals are manufactured in large-scale stainless-steel piping and vessels, with downstream processes taking place within rigid and inflexible facilities. Although process steps such as harvest, purification, fermentation, filtration, dispensing, and freezing require flexibility, stainless steel has not been replaced yet by single-use systems at a large scale. However, manufacturers wanting to optimize process efficiency and scalability to obtain a viable and valuable product for commercial use inevitably will need single-use technology. Aseptic fluid management with single-use systems offers numerous…

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

Overcoming the Productivity Bottleneck in MAb Capture

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It is no secret that progress toward intensifying monoclonal antibody (MAb) production processes has focused on upstream steps. Although the industry welcomed increased production, that also created bottlenecks in downstream processing, including during capture chromatography steps. Technologies that are intended to alleviate such bottlenecks must meet four important criteria to increase productivity and profitability. They must • improve productivity of the MAb capture process, such as by purifying more MAbs, using less media, and/or reducing timelines. • perform as well…

October 20, 2022

Applying Quality By Design Principles to AAV Manufacturing

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The expectation to apply quality by design (QbD) principles to new manufacturing processes has been voiced by regulatory authorities for over a decade (1, 2). They recognize that because of the generally low patient populations for emerging therapies, such as adeno-associated virus (AAV)-based therapeutics, available chemistry, manufacturing, and controls (CMC) information might not be as exhaustive as for other biologicals such as monoclonal antibodies (3, 4). Other challenges include the need for rapid development to address currently unmet medical needs…

October 20, 2022

A Plug-and-Produce GMP Plant for Cell and Gene Therapies Part 2: Rapid Deployment of a Commercial-Scale Facility

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Extending the use of approved advanced-therapy medicinal products (ATMPs) to the tens of thousands of patients who could benefit from such treatment requires a 10- to 100-fold production scale-up. Given that each autologous ATMP batch yields one dose for one patient, expanding production throughput is not a question of boosting volume, but rather of amplifying single manufacturing runs. That is, scale-up is actually scale-out, and the dimensions of the ensuing endeavor extend beyond what occurs in the cleanroom. Coupled with…

October 20, 2022

Two-Step Monoclonal Antibody Purification Using a Multicolumn Continuous Chromatography Platform

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Biomanufacturers typically have relied on multistep processes for optimal removal of impurities such as host-cell proteins (HCPs), DNA, adventitious viruses, and aggregates. However, additional purification steps increase downstream expenses significantly, including costs of supplementary resin, hardware, and buffers. The substantial footprint required at a processing site and additional time needed to perform a complete multistep purification process also increase production costs and complicate process execution. Thus, it is imperative to design and test effective purification procedures for high-quality biotherapeutics, but…

October 20, 2022

Investigation of HCP Enrichment During CGMP Scale-Up

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On paper, scaling a bioprocess from a 10-L to a 100-L to a 2,000-L bioreactor may seem like a straightforward math problem that could be solved by software. In practice, however, the exercise relies on a complex set of biological, chemical, and engineering assumptions; on maintenance of healthy cell cultures; and on management of equipment and analytics while adjusting to each increase in scale (1). Process development and quality control groups need to monitor how scale-up might affect critical quality…

October 20, 2022

Bridging Anti-CHO HCP Antibodies: From Two Third-Generation Cygnus CHO HCP ELISA Kits By AAE-MS

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A well-developed, broadly reactive, and qualified enzyme-linked immunosorbent assay (ELISA) is the gold-standard method for ensuring removal of host cell proteins (HCPs) and demonstrating process consistency and final drug substance (DS) purity. Regulatory guidelines require sponsors to use orthogonal methods for demonstrating antibody coverage of individual HCPs and provide a comprehensive assay qualification package to ensure that the ELISA is fit for purpose. In a June 2022 webinar, Eric Bishop (head of R&D and custom development services at Cygnus Technologies)…

October 20, 2022

From Immigrant to Entrepreneur: Lessons Learned in Building an Innovative Business

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As an entrepreneur, I stepped away from a fulfilling position in a large and established company to go out on my own and build something new. My decision to leave the advanced research department at Illumina, Inc. to create a start-up might seem like an extreme leap, but I am very familiar with the risks of starting over. After earning my bachelor of science degree in biotechnology from the University of Tehran, I immigrated to the United States. I left…

October 20, 2022