Filtration

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

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

A UF–DF Screening System for Bioprocess Development: Efficient and Cost-Effective Process Fit and Scale-Up to Manufacturing

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Ultrafiltration and diafiltration (UF–DF) of therapeutic proteins are performed in either tangential or crossflow mode using membrane filters. UF–DF plays a critical role in both downstream and upstream processes for the biopharmaceutical industry (1). In upstream production processes, classical tangential-flow filtration (TFF) or alternating tangential-flow (ATF) systems are used in high–cell-density perfusion for protein expression by cell culture (2). TFF is used in downstream processing for UF–DF and concentration of therapeutic proteins. TFF unit operations are common in protein purification…

September 15, 2018

Filter-Based Clarification of Viral Vaccines and Vectors

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Viral vaccines rely on the antigen properties of a virus or virus-like entity to trigger an immune response and induce immune protection against a forthcoming viral infection. Through development of recombinant viral vaccines, developers can reduce risks associated with the presence of live and inactivated viruses. Instead, recombinant vaccines induce immunity against a pathogen by relying on the capacity of one or more antigens delivered by means of viral vectors or the baculovirus/plasmid system (1). Viral vaccines are formulated with…

April 19, 2018

IgG Purification By Ultrafiltration: Time for Another Look

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One of the early disappointments in development of immunoglobulin G (IgG) purification technology was ultrafiltration on membranes with 50–100 kDa cutoffs. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that most host cell proteins were smaller than that. IgG was retained. Parallel concentration and buffer exchange could be performed going into a follow-on polishing step. These features made it an obvious candidate for initial capture, but it did not perform as hoped. Membrane fouling sabotaged its concentration–diafiltration potential, and prohibitive…

March 23, 2018

Advanced Viral Clearance Study Design: A Total Viral Challenge Approach to Virus Filtration

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Biologics derived from mammalian organisms have been accepted for therapeutic use for almost a century (1). However, these pharmaceuticals have the potential for contamination with pathogenic adventitious agents such as viruses. With cell-line–derived recombinant proteins, the viral risks commonly include viruses in the Retroviridae and Parvoviridae families (2). As patient safety and manufacturing facility suitability became significant concerns in the 1980s and 1990s, several industry and regulatory bodies reached consensus on how to approach the unique challenges of viral safety…

March 23, 2018

Evaluating Adsorptive Filtration As a Unit Operation for Virus Removal

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Most recombinant monoclonal antibodies (MAbs) are produced by mammalian cells. Because biopharmaceuticals derived from mammalian tissue culture carry the risk of adventitious virus contamination, regulatory agencies expect risk-mitigation strategies to include validation of purification unit operations for their ability to clear viruses (1). Guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) describe how to prove viral clearance in downstream purification processes using an orthogonal approach (2). Viral log10 reduction values (LRVs) are…

March 23, 2018

eBook: Development of a Representative Scale-Down UF/DF Model: Overcoming Equipment Limitations and Associated Process Challenges

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Scale-down models (SDM) are physical, small-scale models of commercial-scale unit operations or processes that are used throughout the biopharmaceutical industry for validation studies, commercial deviation investigations, and postapproval process improvements. To support these studies, regulatory guidelines state that SDMs should be representative of the commercial process. For some downstream unit operations such as column chromatography, developing a representative SDM is straightforward because a linear scale-down approach can be used. However, developing a representative SDM for other downstream unit operations such…

February 27, 2018

New Dimensions in Single-Use Filtration

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Whether viral vectors are clarified or the bioburden after cell harvest needs to be reduced to recover antibodies, such applications in biopharmaceutical production require large filtration areas. Single-use technologies are indispensable in many such bioprocesses. Although some single-use filter assemblies have reached their limits, Sartorius Stedim Biotech has made developments to revolutionize these production steps. Scale-Up Limitations in Single-Use technology Conventional stainless steel process systems have been established for decades in the pharmaceutical industry. They are the basis of safe…

February 14, 2018

Scaling Considerations to Maximize the High-Area Advantage

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Maximizing filtration-area density is a design strategy to minimize filter footprint and improve filtration process economics. Pleated membrane formats commonly are used to achieve that goal for sterilizing-grade filters operating in dead-end mode (also known as normal-flow filtration). Although high-density pleat geometries increase productivity for a device, such formats can present unique challenges. One of the most common concerns is that pleat formats can introduce flow resistance that impedes a device’s filtration efficiency, particularly for high–pleat-density geometries (1, 2). Filtration…

May 18, 2017