Downstream Processing

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

An Integrated Bioprocess for Antibodies: From Harvest to Purified Bulk in Six Hours

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Antibody production platform processes have been widely adopted in biomanufacturing, but many unit operations are not suitable for integration and automation. Here we describe the work of integrating unit operations by transforming a column operation to a more robust cassette format. We have selected a biomolecule-friendly buffer (phosphate) to eliminate, or delay, the performance of a circulating tangential flow ultrafiltration/diafiltration (UF/DF) operation, so the harvest-to-purified-bulk process can be integrated, resulting in a single, direct-flow operation, that reduces the batch process…

June 12, 2019

Making Downstream Processing Continuous and Robust: A Virtual Roundtable

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Current biomanufacturing is driven to pursue continuous processing for cost reduction and increased productivity, especially for monoclonal antibody (MAb) production and manufacturing. Although many technologies are now available and have been implemented in biodevelopment, implementation for large-scale production is still in its infancy. In a lively roundtable discussion at the BPI West conference in Santa Clara, CA (11 March 2019), participants touched on a number of important issues still to be resolved and technologies that are still in need of…

June 12, 2019

On Continuous Chromatography: A Conversation with Sanofi’s George Weeden

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George S. Weeden, Jr., is a scientist in global manufacturing science and technology (MSAT) process science at Sanofi. We recently chatted about the topic of continuous chromatography. What are the general reasons for companies to consider continuous chromatography? And what are the caveats? The main driver for considering continuous chromatography is reducing the cost of goods (CoG). Continuous chromatography improves productivity (mass of product per volume of stationary phase over time) and thus increases throughput or decreases volumes of stationary…

June 12, 2019

Modeling Virus Clearance: Use of a Noninfectious Surrogate of Mouse Minute Virus As a Tool for Evaluating an Anion-Exchange Chromatography Method

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Viral safety is a critical focus during biopharmaceutical manufacturing (1–5). Although well-characterized mammalian cells such as the Chinese hamster ovary (CHO) line have been used for decades, both endogenous expression of retroviral-like particles and exogenous contamination events from viruses warrant continued vigilance (6, 7). International regulatory agencies require biomanufacturers to validate the “viral clearance” efficacy of their downstream manufacturing process steps before resulting products can be awarded clinical trial or commercial approval (8–10). Currently, viral clearance testing is based on…

May 17, 2019

eBook: Making Filtration Work

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Steady improvements in batch-fed cell culture have led to bottlenecks in downstream processing. Filter suppliers are working to improve available tools for purifying therapeutic proteins, to wring every possible efficiency out of those tools, and to make them operate together harmoniously. The combination of high titers and high-value products places a premium on preventing yield loss. Bioprocessors want to optimize filtration primarily for cost reasons. In this eBook, author Angelo DePalma discusses financial aspects, clarification/harvest and virus filtration options, and…

April 25, 2019

Scientific and Technological Advancements in Applications of Single-Use Technology: A Conference Report

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Single-use technology (SUT) has been used increasingly both in clinical and commercial biomanufacturing (1). Proven major advantages include relatively low capital investment, elimination of batch-to-batch cross contamination and reuse cleaning validation efforts, flexibility in manufacturing, and shortened product lifecycles. However, some challenges and barriers to implementation remain: Consumables costs are increasing. Specific regulatory guidance is lacking, as is component interchangeability and standardization. And few if any leak-proof components/systems are available. International groups and associations focused on setting best practices and…

April 17, 2019

Continuous Chromatography: Experts Weigh in on the Possibilities and the Reality

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Discussions of continuous processing in the biopharmaceutical industry are an important part of current efforts toward intensifying bioproduction and bioprocessing. Biomanufacturers are looking at all components of their development and manufacturing processes for ways to reduce the size of their facilities, lower costs, and increase speed and flexibility of operations. Increasing options for and availability of single-use technologies have been major enablers of myriad attempts to improve efficiencies. Although the general consensus may still be that single-use components are more…

February 28, 2019

Tangential-Flow Electrophoresis: Investigation of Factors Involved in an Effective Separation of Human Serum Albumin from Human Plasma

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Human plasma is a complex mixture of biomolecules such as serum albumin, immunoglobulins, coagulation factors, and others (1). These important protein biomolecules often are present at low levels or lacking in affected patients with certain life-threatening conditions. To extract those valuable proteins, a number of purification methods have been developed over time. Plasma fractionation can be traced back to the middle of the 20th century, when Edwin Cohn of Harvard University developed the first industrial process to purify proteins from…

February 14, 2019

Development and Application of a Simple and One-Point Multiparameter Technique: Monitoring Commercial-Scale Chromatography Process Performance

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In commercial-scale biopharmaceutical manufacturing, downstream chromatography steps are still a bottleneck and contribute to significant operational costs (1, 2). Some of those costs are inherent (e.g., resins, large buffer quantities, and cleaning) whereas others are avoidable (e.g., product loss due to rejected lots or deviations that result in production downtime). Maintaining efficient and robust chromatography process performance is therefore critical for minimizing operating costs. To do so, we introduce a simple and one-point multiparameter technique (SOP-MPT) for monitoring chromatographic process…

December 14, 2018