Downstream Processing

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

eBook: Chromatography — Addressing Pain Points To Mitigate Downstream Bottlenecks

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Compared with significant advances in upstream production of recombinant proteins, downstream purification processes have undergone far less development over the past twenty or thirty years. Technologies are emerging for continuous-mode and/or multicolumn chromatography (MCC) operations, but commercial-scale biomanufacturing operations still rely on chromatography equipment and processes that closely resemble those used at the advent of monoclonal antibody (MAb) manufacturing. Thus, chromatography operations generally have not kept pace with upstream gains, resulting in manufacturing bottlenecks at purification stages. Compounding that concern…

September 30, 2022

Development of a Stand-Alone Monitoring Application for Purification Processes in Biomanufacturing

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The ability to monitor unit operations in biomanufacturing is essential because it enables early fault detection and effective root-cause analysis. Below, we present a case study on the development of a stand-alone, data-driven, process-monitoring application for a biomanufacturing purification process. We review the application’s functionality and highlight its utility using a few examples from commercial manufacturing of a therapeutic protein. Lessons learned from the development of that application also are presented. The progress and performance of a purification process have…

September 28, 2022

Mechanistic Modeling for a Hydrophobic-Interaction Chromatography Process: Use in Vaccine Antigen Purification

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Bioprocess models and simulations are the basis for digital twins, which are virtual representations of physical processes and enabling methods of biopharma 4.0. Early adopters in the industry have shown potential application of this approach in nearly all stages of a product development life cycle. Experts in academia and the biopharmaceutical industry have studied mechanistic modeling as the main method of chromatography modeling. Mechanistic models are mathematical descriptions of physiochemical phenomena. They are based on first principles and thus can…

September 28, 2022

Comprehensive Virus Clearance Evaluation Using Microscale Membrane Adsorbers

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Membrane adsorbers can be a simple and effective choice for anion-exchange (AEX) purification of biopharmaceuticals. However, as Sherri Dolan (global technology consultant for virus clearance at Sartorius) explained during a May 2022 presentation, biomanufacturers generally do not leverage their membranes’ full loading capacities. Doing so could improve process economics and decrease costs for several downstream applications. Dolan’s Presentation Membrane adsorbers are ideal for flow-through AEX applications (e.g., secondary purification and polishing) because they can be used at high flow rates…

September 28, 2022

Next-Generation Software Solutions for Analytical Chromatography Processes

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High-performance liquid chromatography (HPLC) has become a leading analytical method for biopharmaceutical process development and optimization, particularly for therapies that leverage plasmid DNA (pDNA), messenger RNA (mRNA), and viral vectors. In July 2022, Blaž Goričar (manager of process analytics development at BIA Separations, a Sartorius company) demonstrated the features of his company’s PATfix software for HPLC data processing and analytics. He described how the program can simplify method execution and enhance evaluation of resulting data. Goričar’s Presentation PATfix software is…

September 28, 2022

High-Selectivity HPLC mRNA Analytics: Quantification and Characterization

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Robust and precise chromatographic analytical methods are key for the efficient development of the mRNA production process. Three different analytical methods, which utilize three different column chemistries, are embedded in a ready-to-use PATfix™ HPLC analytical platform to support mRNA process development and product quantification and characterization. Fill out the form below to download the full report from BIA Separations, now a Sartorius Company.  

September 14, 2022

Perspectives on Bioseparation and Single-Use Centrifugation

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Although single-use technologies have been part of downstream processing for at least 20 years, single-use centrifugation systems have been developed only in the past decade. They offer significant advantages over traditional centrifugation methods, and suppliers are developing single-use centrifuge lines for shear-sensitive applications. To enrich our understanding of the past 20 years of bioprocessing, BPI distributed questions to supplier companies. Below, Tiffany Rau (owner and principal consultant of Rau Consulting) provides her perspective on the breakthroughs in bioseparation and the…

August 22, 2022

20 Years of Advancements in Bioseparations

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Over the past 20 years, the biopharmaceutical industry has made significant advancements in the way that biopharmaceuticals are produced. That principally has been driven by innovative new therapies and demands for greater availability of affordable biotherapeutics. Although the industry has made numerous performance improvements from cell line development and protein expression to bioseparations, downstream processing has presented the industry with its greatest obstacles. For efficient processing and improved yields, step yields should be high (preferably >95%), and the number of…

August 22, 2022

Empowering the Next Revolution

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Over the past 20 years, the bioprocessing landscape has undergone multiple transformations. Some of those were driven by biological innovations as new therapeutic platforms and modalities were introduced; others were driven by advancements in engineering and applied technologies such as single-use solutions, automation, and artificial intelligence. But the industry’s mission of making life-saving medicines that are effective, safe, and affordable remains the same. It’s rewarding to work in a field that aims to improve people’s health and life expectancies and…

August 22, 2022