Culture Development

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Providing Lipids Boosts Protein Productivity: Testing a Feed Supplement with Multiple Cell Clones and Media Formulations

As the biologics (and now biosimilar) markets continue to grow, pressure increases on biomanufacturers to reduce cost of goods sold (CoGS). One way they can reduce cost is by increasing protein productivity in terms of protein titer per volume of culture. Media optimization is a key strategy for increasing protein productivity. In the past few decades, average titers across the industry have increased greatly — from <0.5 g/L in the 1980s to >3 g/L today, and it is not uncommon…

A YouTube video shows the RAMbio mixing system in action. (WWW.YOUTUBE.COM/WATCH?V=AFUE56BV85G

Orbital Shaking and Acoustic-Resonance Mixing: Comparing Culture Characteristics

Production of recombinant proteins usually happens in suspension cultures, with oxygen limitation playing a major role. Oxygen and nutrition feeds are of great significance to aerobic suspension cultures. Oxygen is often the controlling factor in orbital shaken systems because oxygen transfer occurs only through diffusion, which is limited by gas-exchange surface and mixing characteristics. Here, we compare growth characteristics of microbial cultures in a standard shaken incubator with those of cultures in a RAMbio fermentation system, paying particular attention to…

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Process- and Product-Relate Impurities: Part 1 – Process-Related Impurities An Overview

Introduction by Cheryl Scott The CMC Strategy Forums focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of forum meetings are published in BioProcess International and on the CASSS website (www.casss.org). This process is meant to help ensure that biopharmaceutical products manufactured with advancing technologies in a regulated…

Ask the Expert: Cell Culture Media Supplementation

with Dr. James Brooks (BD Biosciences) Improvements in cell culture media and supplementation have enabled significant advancements in bioproduction titers. But optimization to meet the specific needs of individual production cell lines is key to achieving desired production and protein quality, especially for biosimilars. Not only is it desirable to achieve cost-effective levels of production, but quality characteristics also are essential — and for biosimilars must closely resemble those of the originator molecules. Fully chemically defined (CD) media formulations are…

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Bioreactor Design for Adherent Cell Culture — The Bolt-On Bioreactor Project, Part 3: Containment, Sterility

The Bolt-on Bioreactor (BoB) project is an independent initiative aimed at developing and commercializing a bioreactor for the automated and efficient culture of adherent cells, especially for application in the production of therapeutic cells and other biopharmaceuticals (1). After conducting thorough research on available culture systems for adherent cells, the BoB team believes that a successful alternative to existing devices must answer four major challenges. Addressed in the first article of this series (2), the first challenge has to do…

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Ask the Expert: Accelerating Bioprocess Development Using Shake-Flask Metabolic Activity Data

with Dr. Gernot John of PreSens Precision Sensing GmbH Shake flasks are simple, low-cost devices widely used in screening and media optimization. The most widely measured parameter to determine biomass is optical density (OD). It is typically measured offline because no suitable equipment for broad range biomass measurements in shake flasks has been available. But a new, compact, SFR vario device from PreSens Precision Sensing can be placed under shake flasks to measure four parameters online: pH, O2 saturation, oxygen…

Photo 1: Single-use microscale bioreactor with impeller used on the ambr workstation

Reducing Timelines in Early Process Development – Using a Multiparametric Clone-Selection and Feed-Optimization Strategy

The market for biopharmaceutical products remains highly attractive to small biotechnology companies and big pharmaceutical corporations alike (1). Most leading market products are made using recombinant technology (2). Pressures are continually increasing on process development groups to reduce development costs and timelines for taking new clinical products forward from product research bench scale into initial clinical evaluation studies. For many years a recognized critical bottleneck in development of products from mammalian cell lines was selection and isolation of stable, high-producing…

Photo 2: The fully automated ambr250 system controls up to 24 × 250-mL bioreactor experiments

Automated Mini Bioreactor Technology for Microbial and Mammalian Cell Culture: Flexible Strategy to Optimize Early Process Development of Biologics and Vaccines

The use of mammalian and microbial cells in the production of biologics and vaccines is well established, and the majority of the top 10 drugs are now manufactured in this way. There is a significant and growing pipeline of new biologics (1), which in combination with increased pressure on cost reduction and generic competition from biosimilars (2), means that many biopharmaceutical companies are looking for ways to improve productivity in their development laboratories to ensure that upstream processes are efficient…

Bayer Healthcare

Fed-Batch Cell Culture Process Development: Implementing a Novel Nutrient Additive for a Robust, High-Titer, Scalable Process

The fed-batch culture of Chinese hamster ovary (CHO) cells has become well established as the primary method of manufacturing therapeutic recombinant protein products for various disease indications. Fed-batch process-development approaches focus on supporting high–cell-density cultures that are crucial to achieving high product titers but lead to proportionately high nutritional demands. Exhaustion of key nutrients negatively affects cell growth and ability to produce recombinant proteins. To counter that problem, concentrated feeds are added to the culture. Such feeds tend to be…

Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell-Derived Products, Part 1 — Concept

Implementing continuous process improvements is increasing in priority for the biopharmaceutical industry. Such implementation can be driven by product safety, purity, and stability enhancement opportunities as well as by cost-reduction pressures. Companies invest in projects to improve product quality assurance, safety, and yield as well as production efficiency (1). Such changes may come at any process stage, from early cell-growth methods through final-product packaging improvements. Examples include growth medium optimization, purification column operation optimization, and enhanced recovery during final filling…