Upstream Processing

Cell Cultivation Process Transfer and Scale-Up

Discovery, development, and commercialization of novel biologics frequently involve collaboration between two or more companies. In the context of these business relationships, transfer of technology from one institution to another is a crucial step that needs to be executed flawlessly and rapidly. Follow-up activities usually include the development of productive, reliable, and scalable processes and are equally important because they are usually on the critical path to market. PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: TECHNOLOGY TRANSFER (PRODUCTION) AND ANALYTICAL METHODS DEVELOPMENTWHO…

Development of an Antibody Screening Assay for Selection of Production Cell Lines

Biopharmaceuticals such as recombinant monoclonal antibodies (MAbs) account for a significant proportion of all new drugs (1,2,3). Although manufacturing site capacities have expanded and process efficiencies have improved greatly, there is still some concern the current biomanufacturing capacity worldwide might not meet increasing market demands (1, 2). PRODUCT FOCUS: RECOMBINANT PROTEINSPROCESS FOCUS: PRODUCTION PROCESS DEVELOPMENTWHO SHOULD READ: QA/QC, PROCESS DEVELOPMENT, AND ANALYTICAL PERSONNELKEYWORDS: CELL LINE DEVELOPMENT, SCREENING ASSAY, MONOCLONAL ANTIBODIES, FC PROTEINS, CHO, IGG, HTRF, ANTIBODY TITER, CELL LINE PRODUCTIVITY,…

Moving On in Cell Culture

Record-breaking titer outputs in mammalian cell culture systems in the past few years have pushed the industry to a new crisis of sorts: resolving the downstream bottleneck. However, the cell culture and fermentation groups at biopharmaceutical companies aren’t yet ready to sit back and rest on their laurels. Instead, they are moving forward, tackling the downstream issue with upstream modifications and continuing their drive for more cost-efficient processing. The Cell Culture and Upstream Processing track will focus on cell culture…

Near-Infrared Spectroscopy for Rapid, Simultaneous Monitoring

The use of cellular physiology to make target molecules has been practiced for centuries, with early examples being the production of wine and beer through yeast fermentation. Single (e.g., bacteria and yeast) and multicellular (plant or animal) organisms can be harnessed to produce otherwise chemically complex, low-yield, or chemically uncharacterized materials. These include “lock-and-key” receptor complexes with perfect stereochemical specificity, large-scale protein scaffolds, or antibiotics. One example is penicillin, with a sensitive β-lactam ring structure at its core (1). Mass-production…

Automated Closed-Loop Solution for Bioreactors and Fermentors

Today, there is much discussion regarding the promise of improved insight into bioprocess industry processes. Look to the pages of industry publications such as this one, and you’ll see that industry leaders in process measurement and control have begun to discuss openly the potential for simulating and modeling bioprocesses. “Important opportunities such as the application of mass spectrometers, dissolved carbon dioxide probes, and inferential measurements of metabolic processes have come to fruition today opening the door to more advanced process…

Bioassay Survey 2006–2007

Bioassays are required for a variety of purposes in the development and production of biopharmaceuticals including drug candidate selection, product releases, product stability assessment, and comparability to support proposed process changes. However, because of their complexity and susceptibility to many variables, bioassays often prove problematic and difficult to develop. Timely development of suitable assay systems represents a major investment on the part of the biopharmaceutical industry — but late development often results in even more costly clinical holds. PRODUCT FOCUS:…

Cell Cultivation Process Transfer and Scale-Up

The introduction of therapeutic monoclonal antibodies (MAbs) has greatly revolutionized therapies for several cancer immune disorders (1,2,3,4,5). Benefits to patients have been substantial, translating into both increased life expectancy and improved quality of life. Currently, twenty-one therapeutic MAbs are registered for marketing in the United States, with the introduction of several more expected in the coming years (6,7,8,9,10,11). PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: Technology transfer (production) and analytical methods developmentWHO SHOULD READ: PRODUCTION AND PROCESS DEVELOPMENT, MANUFACTURINGKEYWORDS: IGF-1R, EXPRESSION, TECH…

Process Monitoring in Suspension–Adapted CHO Cell Cultures

Suspension-adapted Chinese hamster ovary cell (CHO-S) cultures are widely used in biotechnological production of recombinant proteins. In fact, such special cell lines have become the standard for this type of biopharmaceutical production (1). The reasons for that include their fast reproduction, high protein expression rate compared with other eukaryotic cells and, above all, the glycosylation patterns generated by the cells (2, 3). PRODUCT FOCUS: Animal cell products (recombinant proteins)PROCESS FOCUS: Production and product developmentWHO SHOULD READ: Process and cell culture…

Integrated Strategies for Clone and Media Formulation Selection

Clone selection techniques used for development of stable, high-expressing recombinant cell lines suitable for robust fed-batch cell culture processes are critical for biopharmaceutical manufacturing. Basal media screening, feed development and addition strategies, and fed-batch bioreactor performance are all intimately tied to overall performance of the clones during scale-up. Serious issues can arise if a high-quality clone is not established, such as low or unstable protein yield and ineffective use of costly resources. PRODUCT FOCUS: Recombinant proteinsPROCESS FOCUS: ProductionWHO SHOULD READ:…

Recommendations for Extractables and Leachables Testing

Extractables and leachables from disposable manufacturing systems must be addressed as part of process validation. Extractables are compounds that can migrate from a material into a solvent under exaggerated conditions of time and temperature. Leachables are compounds that actually do migrate into a drug product formulation under normal processing conditions. All materials have extractables and potentially have leachables. When properly evaluated, both are easily addressed and rarely lead to disqualification of a disposable component. PRODUCT FOCUS: ALL BIOLOGICSPROCESS FOCUS: MANUFACTURINGWHO…