Ultrafiltration (UF) is a membrane-based separation technology commonly used in the biopharmaceutical industry for concentration or diafiltration of protein solutions to remove low–molecular-weight (LMW) impurities or exchange buffers. The nominal MW limit of UF membranes ranges from 1,000 Da (1 kDa) to 1,000,000 Da (1,000 kDa). A target product is retained by the membrane while lower-MW solutes or impurities pass through (1). For a target product with a smaller MW than the impurities, separation is accomplished by allowing…
Downstream Processing
New Downstream Harvest Options Using Custom Designed Disposable Resins
Engineered affinity resins create the ability to produce functional proteins on a solid support in vivo which can lower production costs, improve flexibility and increase scale up speed.
Next Generation PEGylation Technology
Decreases in the immunoreactivity of next generation PEGylated drugs may be attainable by the use of monofunctionally activated hydroxyPEGs instead of methoxyPEGs in their synthesis.
Single-Use Depth Filtration for Mammalian Cell Culture Clarification
Clarifying cell culture broth is the first downstream unit operation in an elaborate sequence of steps required to purify a biological therapeutic. A combination of centrifugation, depth filtration, or tangential-flow filtration (TFF) is used for that operation. The availability of large-scale, single-use, depth filtration technology in the recent years, however, has given process developers the capability to improve and simplify downstream processes.
New Technology for Broad Screening of Cell Microbial Contaminants, Including Viruses
Two case studies are presented highlighting the impact PLEX-ID System can have to rapidly identify virus contaminants resulting in better control of biologics manufacturing process, with the potential to characterize various sources of excursion through genotyping information.
Scale-Up of Single-Use Depth Filtration Systems
Process development engineers are responsible for developing scale-up strategies for efficient and cost-effective manufacture of biological and bioprocess-derived products at bench-scale, pilot scale and at manufacturing scale. A central unit operation in the production of these various therapeutic proteins is cell clarification using depth filtration. Recently, single-use depth filtration technologies have been developed, at scales ranging from the lab, to R&D, process development and on to manufacturing.
In this educational webcast, Laura Brown, Scientific Application Support Specialist II with 3M Purification, will provide guidelines for scaling-up of single-use depth filtration systems, and will review the commonly used single-use depth filtration products used for biopharmaceutical manufacturing.
Vertical Integration of Disposables in Biopharmaceutical Drug Substance Manufacturing
Single-use (disposable) technologies are gaining significant traction in biopharmaceutical manufacturing due to reductions in capital investment for plant construction, lower requirements for cleaning and sterilization, and the advantages of eliminating cross-contamination during multiproduct manufacturing (1,2,3,4). In the early days of disposables, single-use (SU) systems were used only in specific unit operations (5, 6). Recently, however, options have become more widely available throughout drug-substance manufacturing (7,8,9,10). Companies now focus on selecting the right SU technology from an array of…
Sterilizing-Grade Filter Sizing Based on Permeability
Sterilizing filtration renders biotherapeutics free of biocontamination. In many cases, sterilizing-grade filters also reduce bioburden or facilitate closed or aseptic processing. They are used to filter active pharmaceutical ingredients (APIs), formulated bulk, cell culture media, buffer, additives, process intermediates, and so on. Such applications are often critical for ensuring a successful batch operations. Nonetheless, a significant amount of time and resources are typically not devoted to establishing filter sizing requirements for “simple†applications such as buffer filtration. Here,…
A Decade of Processing
About halfway through our first decade in publication, we became well acquainted with a new buzzword phrase in the biopharmaceutical industry: downstream bottleneck (1). This followed on the heels of a manufacturing capacity crunch that had been forecast shortly before BPI made its debut. Thanks to herculean efforts by upstream process and cell-line engineers, that crunch didn’t pan out. In its place, however, high-titer production moved the pressure downstream. Now separation and purification engineers were tasked with handling…
A Decade of Harvesting Methods
The preliminary separation of a protein of interest from a reactor “soup†of process impurities (e.g., cell debris, colloids, lipids) is the first step in a downstream process. It is also a primary step that introduces a significant risk of product degradation, bioburden concerns, or process errors, especially if a harvest method is not a good “fit†with a newly designed bioreactor (e.g., single-use) or fermentation vessel. In 2003, BPI’s first year, industry concerns revolved around potential capacity…