Downstream Single-Use Technologies

Examining Single-Use Harvest Clarification Options: A Case Study Comparing Depth-Filter Turbidities and Recoveries

Steadily increasing demand for biopharmaceutical drugs has led the industry to examine its manufacturing scales while pressuring research and development groups to produce high-yielding clones and processes. Improved media, feed supplements, bioreactor designs, and control of process parameters have helped biomanufacturers achieve multifold increases in volumetric productivity from production bioreactors. However, cell culture processes are significantly affected by their bioreactor’s ability to support cells at higher densities and sustain cultures at lower viabilities. With the implementation of a number of…

Downstream Disposables: The Latest Single-Use Solutions for Downstream Processing

Downstream processing has been considered a “bottleneck” in the manufacture of protein biotherapeutics ever since cell culture engineers began dramatically improving production efficiencies around the turn of the century. And as single-use technologies have grown in importance and acceptance, offering more solutions every year, their biggest challenges too have been in the separation, purification, and processing that follows product expression in cell culture. Many of the technologies familiar to process engineers — e.g., centrifugation and chromatography — present technical and…

Single-Use Depth Filters: Application in Clarifying Industrial Cell Cultures

For current process development phases, many biomanufacturers’ attention is directed increasingly to the first unit operation in downstream processing, which is the removal of cells and cell debris from culture broth and clarification of supernatant containing a biopharmaceutical product. Given the high cell densities achievable with both mammalian and microbial cell culture processes, primary recovery can be a significant challenge. The current trend in cell culture is to increase product titers with enriched culture media, improved cell productivity, and increased…

Multicolumn Chromatography: Facilitating the Commercialization of Monoclonal Antibodies

Since 2001, global contract development and manufacturing organization (CDMO) CMC Biologics has completed more than 120 projects with at least 100 pharmaceutical partners. During that time, the company has taken a holistic approach to helping clients balance manufacturing risks and rewards. The team focuses on evaluating key technologies to deploy a constantly evolving set of capabilities in support of biopharmaceutical clients throughout their product lifecycles. Part of that commitment is continually evaluating what would best benefit customers and where key…

Membrane Adsorbers, Columns: Single-Use Alternatives to Resin Chromatography

Filtration membranes are used extensively throughout the biopharmaceutical industry for a range of applications, from coarse filtration to nanofiltration. Advantages of filter technologies include easy scaling, disposability, and (for many membrane filters) rapid and robust performance in a single-pass. The same advantages have been realized with membrane adsorbers. Chromatography resins are inherently disadvantaged by diffusion limits of the pores in chromatography media. Therefore, resin columns must be significantly oversized to match the performance of high productivity bioreactors. By comparison, membrane…

Accelerated, Seamless Antibody Purification: Process Intensification with Continuous Disposable Technology

Process intensification through continuous manufacturing has been practiced in the chemical, petrochemical, and food industries for years and has gained much interest among biopharmaceutical manufacturers (1). Key drivers encouraging biomanufacturers of therapeutic molecules to convert batch processes into continuous operation include flexibility, productivity, cost effectiveness, and product consistency. Continuous upstream processing has been demonstrated for the manufacture of a broad range of molecules, including complex/labile proteins such as enzymes (2) and monoclonal antibodies (3). Recent publications have reported successful application…

Diatomaceous Earth Filtration: Innovative Single-Use Concepts for Clarification of High-Density Mammalian Cell Cultures

In the past decade, biopharmaceutical manufacturers have demonstrated major improvements in monoclonal antibody (MAb) production, exhibiting product titers frequently in the range of 5–10 g/L using standard fed-batch mammalian cell cultures (1, 2). Increased product yields allow for smaller-scale production vessels. With 2,000-L single-use bioreactors already commercially available, single-use manufacturing of biomolecules becomes more and more an option. Other recent developments in the biopharmaceutical industry — e.g., drugs for smaller indications and more potent drugs allowing for lower dosages —…

Industry Experts Convene in New York to Discuss Latest Innovations: A BPI Special Report

As the biopharmaceutical industry continues to mature and grow, so too does the need to educate a broader audience of biopharmaceutical professionals interested in hearing, understanding, and applying the latest science and technology trends that support and in many cases are transforming today’s bioprocesses. To reach this extended and engaged audience, BioProcess International created the BPI Theater Series: a live, interactive program that provides bioprocessing content to traditional, noncore biopharmaceutical conference programs. It provides attendees with the opportunity to interact…

Enabling Greater Process Control and Higher Protein Titers: Advances in Downstream Single-Use Technologies

Downstream protein purification (the stage in which a protein is isolated and purified) is one of the last steps in biotherapeutic manufacturing. Single-use technologies are an increasingly popular choice for both upstream and downstream bioprocessing because they offer significant benefits over traditional multiuse manufacturing systems. Single-use technologies also provide an array of logistical benefits, including reduced costs, minimized risk of cross-contamination, and improved operational efficiency (1). Challenges remain, however, in designing a complete, streamlined, single-use process for downstream protein purification.…

Industry Adoption of Membrane Adsorbers

Membrane adsorbers (MAs) are the fastest-growing segment in single-use bioprocessing. But their future is not entirely certain. According to BioPlan Associates’ latest survey of biopharmaceutical manufacturing, the MA market has been growing at ~20% annually since 2006 (1). Paradoxically, however, the segment may not be a true “rising star.” Our study also shows that MAs remain among the least-often adopted devices among biomanufacturers. So the question of how and whether MA technology can revolutionize bioprocessing remains open. Market for Membrane…