2018

Seamless Transition from R&D to Manufacturing

Fast and cheap: These criteria are becoming ever more urgent drivers for manufacturers of biologics, faced with increased scrutiny on the costs of developing novel drugs, the lengthy timelines for delivering these drugs to patients, and the tightening competition to capitalize on new targets. The challenge for manufacturers is further heightened by the expectations to deliver on quality as well. Although development and production of molecules such as monoclonal antibodies (MAbs) have greatly benefited from the “platformization” of core technologies…

Setting Up a Rapid Mycoplasma Assay to Support Recombinant Protein Production

Octapharma AB (OAB) in Stockholm, Sweden, is the site for Nuwiq human recombinant factor VIII (FVIII), production. The drug is produced in a human cell line cultured in a perfusion bioreactor using a closed system (to minimize contamination) and proprietary serum-free medium without animal-derived components. In accordance with regulatory guidelines, cell banks and cell cultures used for production of biological products must be free of mycoplasma. Traditional mycoplasma testing is a growth-based method that represents a significant bottleneck in quality…

Accelerated Development, Manufacturing and Monitoring of Viral Vectors

The goals of process intensification are to enhance production while shortening timelines, lessening contamination and environmental risks to products and operators, and reducing operating footprints. Previous publications from Sartorius Stedim Biotech (SSB) have highlighted key elements of such activities. In this report, the authors extend the scope of this discussion to tools and technologies that enable intensification of viral vector manufacturing processes. The first article summarizes presentations from a 2018 seminar for viral vaccine manufacturers. Three guest presentations highlighted the…

Accelerating Biopharmaceutical Development with High-Throughput Glycan Screening and Multiple Attribute Methodology

Part 1 Development of biopharmaceuticals comprises many integrated steps, beginning with research and discovery and optimally ending with a commercial therapeutic molecule. Early screening of large numbers of clones and cell culture expression conditions is essential to identifying proteins that carry to greatest likelihood of clinical and commercial success. Part one of this report reviews how high-throughput glycan screening can significantly improve current analytical strategies relating to cell line development. Part 2 Minor impurities and changes in attributes such as…

Culture of 3D Cell Aggregates in Perfusion in a DASbox® Mini Bioreactor System

Three-dimensional (3D) culture systems provide cell–cell and cell–extracellular interactions that reproduce the cellular microenvironment in vivo better than typical two-dimensional monolayers. This property is of paramount importance in many applications, including disease modeling, drug toxicity assessment, and manufacturing of stem-cell–based products (1). Cultivation in stirred-tank bioreactors using perfusion mode opens up new possibilities in the cultivation of 3D cell aggregates. Perfusion allows for removal of detrimental metabolites, cell debris, and proteases from the culture as well as the addition of…

Updating Biologics Manufacturing: Using Modern, Single-Use Powder Handling Reduces Time to Market and the Chance of Contamination

Biopharmaceutical companies are striving to produce biologics more efficiently with a lower cost point and fewer employees. Most small-scale media and buffer operations are carried out with small bottles of liquid media. But as processes are scaled up to manufacturing levels, that is no longer a viable option. Costs of shipping liquid are simply prohibitive, so the industry has migrated to using media and buffer in powder form. In fact, 90% of cell-culture media and buffer for sale is now…

Biopharmaceutical Production in Fed-Batch CHO Cell Culture

Chinese hamster ovary (CHO) cells are used widely in the biopharmaceutical industry for the production of recombinant proteins. In times of rapid growth in the biopharmaceutical market with monoclonal antibodies (MAbs) and biosimilars, the use of chemically defined (CD) feeds and culture media for CHO mammalian cell culture is crucial. Currently, strict regulatory norms for the biopharmaceutical industry has led to the wide use of animal-component–free (ACF) culture processes, including CD media and feeds. A business requires significant amounts of…

Complex Protein Production with MaxCyte’s ExPERT Platform for Streamlined Cell Engineering

Complex proteins present a range of production challenges, including low expression levels, degradation, aggregation, a high degree of posttranslational modifications, and the need to use multiple or large expression plasmids. They also can lead to challenges in producing multi-subunit proteins with correct folding and subunit ratios. MaxCyte’s ExPERT platform for cell engineering alleviates those challenges by facilitating the production of complex proteins with high efficiency and cell viability in your cell line of choice. This technical note summarizes four applications…

Enhanced Ergonomics for Large-Volume Fluid Handling: Safe and Easy Operations with Flexsafe® Single-Use Bags

Built on over 30 years of expertise in large-volume fluid processing with 3D single-use bags, Sartorius Stedim Biotech collaborated with many end users for the large-volume Flexsafe® 3D system with enhanced ergonomics, thereby bringing operator safety to the center of successful drug processing. We conducted in-depth interviews to gather and explore operator insights into the usability of large-volume single-use systems. That input helped us improve our product offering with the aim of also improving workplace health and well being. A…

Hydrogen Bond Chromatography – A New Tool for Enhanced Separation of Proteins from Virus Particles and Other Very Large Biologics

CIMmultus ADC monoliths from BIA Separations are the first chromatography products in the field to exploit hydrogen bonding as the primary binding mechanism. These products bring a unique new selectivity to all purification challenges, but they are especially distinctive in their ability to retain large biomolecules more strongly than small ones. They enhance removal of fragments, aggregates, and viruses from proteins, and they enhance removal of proteins and other small contaminants from viruses and other very large biologics. H-Bond ADC…