Culture Development

Platform Solutions for Cell Therapy Manufacturing

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Advances in cell therapy have resulted in significant progress toward treating some widespread and difficult diseases, many of which represent unmet medical needs. For example, phase 3 clinical trials are already under way for therapies based on mesenchymal stem cells (MSCs), including therapies for graft-versus-host disease, acute myocardial ischemia, and chronic obstructive pulmonary disease (COPD) (1–3). Successful cell therapy treatments for such afflictions will be not only significant medical breakthroughs, but also in very high demand. However, their commercialization is…

February 13, 2017

Setting Raw-Material Specifications Using Prediction Models: Determination of a Specification Limit for a Raw-Material Impurity in mPEG-Aldehyde

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Impurities related to raw materials used for bioproduction can be inadvertently introduced into a manufacturing process, causing potential failure to meet in-process controls or release specifications. Unexpected impurities also can reduce yield and affect the quality, safety, and effectiveness of a final product (1). Raw-material impurities can originate from starting components or reagents used in manufacture. They can be generated in situ during synthesis or as degradation products. Impurities also can result from improper handling, packaging, and storage. Identification and…

January 19, 2017

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

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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…

November 14, 2016

Orbital Shaking and Acoustic-Resonance Mixing: Comparing Culture Characteristics

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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…

May 11, 2016

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

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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…

February 4, 2016

Ask the Expert: Cell Culture Media Supplementation

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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…

October 15, 2015

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

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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…

May 12, 2015

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

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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…

December 11, 2014

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

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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…

November 10, 2014

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

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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…

September 23, 2014