Spending is up, the global economy is slowly getting back on track, and the biopharmaceutical industry continues to roll along at double-digit growth. Productivity has been the primary industry focus over the past few years, and it remains a hot topic. Companies are aggressively going after the bottlenecks to their efficiency, and now they’re opening their wallets to fix what’s broken. One of the biggest productivity fixes today centers on improved single-use devices and systems. They top a…
Downstream Processing
Working with a Powerful and Robust Mixed-Mode Resin for Protein Purification
Orthogonal methods for assuring robust downstream purification are critical to today’s demanding downstream process industry. Regulatory scrutiny on the immunogenic propensity of drugs has increased and broadened over the past two decades. Although immunogenicity can come from a number of sources, common concerns include host-cell proteins and aggregates. Constantly lurking in the background are other issues such as viral clearance, DNA levels, and so on. Those problems can be addressed simultaneously with the mixed-mode chromatographic support known as…
Where Will Technology Take Cell Therapy?
The cell therapy industry’s biggest challenge is in manufacturing. Technologies are needed to support expansion of large numbers of cells for commercial production. A number of sources are presenting options: e.g., standard two-dimensional tissue cultures that “grow up†to Corning HYPERFlask and CellSTACK or Nunc Cell Factory systems; hollow-fiber–based equipment; and disposable bags and traditional stirred-tank bioreactors. Each has its place and application, but how can companies choose among them? Where and when do they initiate scale-up process…
Predicting Virus Filtration Performance with Virus Spike Characterization
Evaluating a virus filter should, in theory, be a straightforward exercise. Membrane-based filtration is a robust virus reduction technology that plays an important role in virus safety for most drug production processes. An appropriate virus filter for a given process is generally selected through preliminary testing with relevant drug feed material. Data acquired during such tests are used to determine hydraulic performance targets such as expected flow rates and total throughputs. A virus clearance evaluation study is then performed in…
Extractables and Leachables
The 13th WCBP CMC Strategy Forum on extractables and leachables was held in Bethesda, MD, in January 2008. The purpose of this forum, cosponsored by CASSS (an international separations society) and the FDA, was to discuss questions related to extractables and leachables in the context of biopharmaceutical manufacturing and find consensus on some of those topics. Morning sessions began with “Extractables and Leachables: Challenges and Strategies in Biopharmaceutical Development†with program cochairs Stacey Ma of Genentech, Inc., Ingrid…
Efficient Aggregate Removal from Impure Pharmaceutical Active Antibodies
Polishing with membrane chromatography (MC) has achieved acceptance as state-of- the-art technology for charged impurities. Traditionally, anion-exchange (AEX) and cation-exchange (CEX) membrane chromatography have been used to remove charged contaminants such as host-cell proteins (HCPs), recombinant DNA, protein A, endotoxins, and viruses. In monoclonal antibody (MAb) processes, polishing steps usually follow a protein A affinity column step. In some cases, CEX capture is applied, either with at least one AEX or a combined AEX and CEX step. The latter may…
Understanding Virus Preparations Using Nanoscale Particle Characterization
As regulators become increasingly stringent in demanding a fuller understanding of whole virus preparations, researchers and manufacturers are looking beyond well-known characterization methodologies. Existing technologies for quantifying and characterizing viral preparations such as infectivity assays, quantitative polymerase chain reaction (qPCR), and protein assays provide crucial information but tell only half the story. We evaluated a unique technology developed by NanoSight Ltd. (www.nanosight.com) for visualizing viruses in liquid suspensions, measuring their approximate concentration, and characterizing their state of aggregation. Information generated…
Modeling Perfusion Processes in Biopharmaceutical Production
Perfusion processes are considered more difficult to model than batch-based fermentation processes because up to a third of a perfusion-based campaign is spent outside “steady-state†production mode. Variabilities in cell density, titer, and harvest rate (HR) during ramp-up necessitate planning and explicit modeling of variabilities in these processes and their subsequent downstream operations. Longer continuous fermentation times require more rigorous attention to risk than do batch-based systems. A flexible purification platform must respond to changing fermentation conditions. Here…
Industrial-Scale Biochromatography Columns Address Challenging Purification Needs
Chromatographic purification remains the most critical step in biopharmaceutical downstream processing. Its purpose is to separate biologic impurities such as host-cell proteins (HCPs), nucleic acids, and oligomers from a target biologic, which must be purified to very high levels (often >99%). Biological separations usually require medium to high salt concentrations and bear inherent risks of microbial contamination in waterbased process streams. Thus they require specifically designed equipment. Depending on process constraints, chromatographic media, and equipment limitations, biochromatographic separations…
Improving Process Economy with Expanded-Bed Adsorption Technology
Most biopharmaceutical processes involve purifying proteins and peptides from various sources. Typically, purification schemes contain multiple unit operations, including several chromatographic steps to ensure safe removal of critical impurities and contaminants. Each step affects the overall process economy by increasing operational cost and process time and by causing product losses. Carefully designing a purification procedure to reduce the number of steps is an efficient way to reach high process economy. Expanded-bed adsorption (EBA) technology is a powerful alternative…