June 2009

The Road to a Fully Disposable Protein Purification Process

    What’s keeping senior biopharmaceutical executives awake late at night? According to BioPlan Associates, Inc., which publishes an annual comprehensive survey of the state of worldwide biopharmaceutical manufacturing, capacity constraints are among the key issues at hand (1). And one of the most important constraints is the lack of physical capacity in purification equipment. Bioreactors are producing a lot more protein than current downstream purification steps are designed for. Overcoming the resulting bottlenecks may require increasing the productivity of…

Making Your Way to Excellence

    As organizations launch operational excellence (OpEx) programs, they are faced with challenges that must be overcome before they can achieve true excellence. One of the largest barriers to overcome is employee perception. The first step is to provide training that will energize employees and change their understanding of what operational excellence can do for them and their organization. For this reason, Bayer has developed an OpEx fundamentals training that starts with the “heart and mind,” focusing on less-threatening…

Single-Use Strategies in Bioprocessing

BioProcess International has followed, from the beginning, the ways in which single-use technologies have transformed the landscape of industrial bioprocessing. On 18 March 2009, we organized a panel session at the annual Interphex conference (Jacob Javitz Center, NYC) to drive discussion toward longer-term implications of single-use components and technologies on the future of bioprocessing. Is their use a cost-saving strategy overall? What economic factors are driving their adoption? The panelists were prepared to address such topics as economic considerations in…

Single-Use, Continuous-Countercurrent, Multicolumn Chromatography

    Manufacturing processes for biopharmaceuticals have undergone significant changes over the past decade. One of the most striking results of improved process sciences is the dramatic rise in expression levels from animal cell cultures. Figure 1 shows how some monoclonal antibody titers have increased about 30-fold over the past 15 years. These increasing titers have allowed current biomanufacturing facilities to produce larger product quantities than anticipated at the time they were designed and built. Figure 1:   As a…

Development and Qualification of a Generic IgG Quantification Assay Using Surface Plasmon Resonance

Fast, precise, and accurate quantification technologies are indispensable for efficient process development in applications such as IgG production in a GXP environment. Based on surface plasmon resonance (SPR) technology, the Biacore C system from GE Healthcare (www.biacore.com) is an alternative technology for IgG quantification that has benefits over traditional methods. Assay development is simplified and accelerated due to real-time detection. Assay hands-on time is reduced, and sample throughput can be increased using automation and efficient data evaluation with regulatory-compliant software.…

Development of a Turn-Key Harvest Solution for Small-Volume Bioreactors

Over the past 10 years, disposable bioreactors have grown from a niche tool servicing small-scale projects to a common and essential component in the CGMP production of human therapeutics (1). Recent advances in filter integration, aseptic connectors, and disposable sensing allow entire cell culture processes to be performed using only single-use components. However, harvest and clarification operations remain largely dependent on centrifugation, cross-flow filtration, and depth filtration (2), which are all techniques that have not been widely adapted to single-use…

A Single-Use, Scalable Perfusion Bioreactor System

We have previously described a patented nonsparging, nonbubbling oxygen transfer method (1). This method is based on interaction between the air-exposed smooth surface of a bioreactor vessel and culture medium repeatedly sweeping across it with a certain force, which seems to generate microscopic bubbles among the water molecules (2). We manufactured high–oxygen-transfer Current suspension bioreactors with working volumes of 5 L, 50 L, 150 L, and 300 L. Here we describe the use of these suspension bioreactors as “artificial lungs”…

Hydrophobic-Interaction Membrane Chromatography for Large-Scale Purification of Biopharmaceuticals

    Biopharmaceutical manufacturing is divided into two areas: upstream fermentation or cell culture and downstream purification processes. Each area contains multiple unit operations. A unit operation is defined as a step in processing using a particular type of equipment. Here, we focus on downstream process development, which must reliably produce a highly purified drug substance (often >99%). Downstream processing includes recovery, capturing, and polishing steps. The primary downstream unit operation is chromatography because of its simplicity and high resolving…

Automated Liquid Handlers As Sources of Error

Use of automated liquid handling equipment for rapid testing and reproducible screening of thousands of molecules, cells, and compounds has become an essential component of life-science laboratories across the globe. Along with an increase in such use, transferred volumes have shrunk, as demands increase on transfer accuracy and precision when aspirating, diluting, dispensing, mixing, and washing. Automated liquid handlers are generally used to increase the productivity and repeatability of volume transfer, but as discussed here, they are still prone to…

A Presanitized, Purpose-Designed, Single-Use TFF Strategy

    For many years, biopharmaceutical manufacturers have worked to increase capacity, address upstream production issues, and improve product yields. Notable successes recently achieved in upstream technology have significantly increased expression rates and therefore, upstream production capacities. Successes in generating higher titers combined with increasingly stringent quality and regulatory requirements have led to a number of challenges in aligning the efficiency of downstream processing with upstream titers. It is generally recognized that downstream processing costs account for about 70% of…