Downstream Processing

Increasing Purity and Yield in Biosimilar Production

Current downstream processing strategies for recombinant proteins often require multiple chromatographic steps, which may lead to poor overall yields. Product purification can be especially difficult when a target protein displays reduced stability, forms isoforms or misprocessed variants, or needs to be purified from a complex mixture containing a high degree of contaminants. One technology that has been developed to tackle such limitations is based on custom-made chromatography matrices containing camelid-based single-domain antibody fragments. With a molecular weight of only 12–15…

A Salt-Tolerant Anion-Exchange Chromatography Sorbent for Flexible Process Development

In most downstream purification processes designed for biopharmaceutical drug production, dilution and diafiltration sequences are unavoidable. Such operations are routinely used to adjust a feedstock or chromatographic fraction to the optimal conditions required for best process performances. Nevertheless, those steps are often time, water, and labor consuming without participating directly in final product purification. Because biopharmaceutical production is increasingly driven by cost reduction, a possible means for enhancing process economics is to streamline purification by eliminating these unit operations before…

“Transformation By Infection”

Every bioprocess begins with an expression system, and every expression system begins with DNA transfection. Derived from transformation and infection, the word paradoxically has come to be applied mainly to nonviral methods of genetically engineering cells; viral-vector–mediated DNA transfer is often called transduction. There are chemical, particulate, physical/mechanical, and viral means of getting new genetic material into a cell, and that DNA may take a number of different forms. Even the cloning method (pictured right) using a microscopic needle to…

Purifying Common Light-Chain Bispecific Antibodies

A bispecific antibody can bind two different antigens. Immunoglobulin G (IgG) type antibodies have two binding sites with different variable regions. An IgG variable region is made up of a variable light-chain sequence (VL) and a variable heavy-chain sequence (VH). The light chains (LCs) of common LC antibodies are identical for both variable regions, leaving the heavy chain (HC) for generating different specificities. Thus, recombinant host cells for production of common LC bispecific antibodies carry genes for both HCs, with…

Artifacts of Virus Filter Validation

Virus filters are used in biomanufacturing to ensure the safety of biopharmaceutical drug products. As part of filter implementation, manufacturers are required to validate that the filtration process can indeed remove virus. Validations are typically performed at contract testing organizations (CTOs) that are “equipped for virological work and performed by staff with virological expertise in conjunction with production personnel involved in designing and preparing a scaled-down version of the purification process” (1). Virus removal capability of a filtration process is…

Broadening the Baseline

When the editors of BPI asked us at BPSA to put together a content-rich article on single-use issues, we were happy to do so. Our challenge was how to bring in multiple viewpoints about the growing business of single-use that would be a “quick read” for the BPI audience. The answer: an expert colloquy. Represented here are several of the most qualified industry spokespersons in single-use — all are members of BPSA and speak as directors of the alliance. Their…

Building and Operating a Single-Use Facility: Reducing Time, Cost, and Risk

This podcast features: Richard Pearce, Director of Strategy and Business Development, EMD Millipore     This podcast was recorded at the 2013 BioProcess Theater which took place at the 2013 BIO International Convention, April 22-25, 2013. The BioProcess Theater, a 50-seat amphitheater located on the exhibition floor at the heart of the BioProcess Zone, provided attendees with daily, complimentary opportunities to listen, learn, and interact with leading experts as they presented, discussed and debated the latest business and scientific trends…

Processing Biologics Using a Disposable Production Train?

This podcast features: David J. Kenyon, PhD, Senior Director, Process Services, Gallus BioPharmaceuticals, Inc.     This podcast was recorded at the 2013 BioProcess Theater which took place at the 2013 BIO International Convention, April 22-25, 2013. The BioProcess Theater, a 50-seat amphitheater located on the exhibition floor at the heart of the BioProcess Zone, provided attendees with daily, complimentary opportunities to listen, learn, and interact with leading experts as they presented, discussed and debated the latest business and scientific…

Purification and Concentration of Nanoparticles using Single-Use TFF

This podcast features: Jim Simmons, Central US Sales Manager, Spectrum Laboratories, Inc.     This podcast was recorded at the 2013 BioProcess Theater which took place at the 2013 BIO International Convention, April 22-25, 2013. The BioProcess Theater, a 50-seat amphitheater located on the exhibition floor at the heart of the BioProcess Zone, provided attendees with daily, complimentary opportunities to listen, learn, and interact with leading experts as they presented, discussed and debated the latest business and scientific trends impacting…

Process Evolution from the Iron Age to the New Age – A Transition from a Stainless Steel and Glass to a Full Disposable Upstream Process

This podcast features: Michael Brown, Senior Associate Scientist, Avid Bioservices, Inc     This podcast was recorded at the 2013 BioProcess Theater which took place at the 2013 BIO International Convention, April 22-25, 2013. The BioProcess Theater, a 50-seat amphitheater located on the exhibition floor at the heart of the BioProcess Zone, provided attendees with daily, complimentary opportunities to listen, learn, and interact with leading experts as they presented, discussed and debated the latest business and scientific trends impacting the…