With the help of rapid advancements in molecular biology and genetic engineering, a rising number of biotherapeutics are being developed and marketed. The quality and safety requirements for this class of active ingredients has steadily increased over the decades since Eli Lilly put forth the first insulin manufactured using genetically modified organisms in 1982. This has led to dynamic developments in protein analysis and proteomics intended to meet a growing demand for new technologies and sophisticated analytical techniques to characterize…
Analytical
Cell Cultivation Process Transfer and Scale-Up
Discovery, development, and commercialization of novel biologics frequently involve collaboration between two or more companies. In the context of these business relationships, transfer of technology from one institution to another is a crucial step that needs to be executed flawlessly and rapidly. Follow-up activities usually include the development of productive, reliable, and scalable processes and are equally important because they are usually on the critical path to market. PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: TECHNOLOGY TRANSFER (PRODUCTION) AND ANALYTICAL METHODS DEVELOPMENTWHO…
Near-Infrared Spectroscopy for Rapid, Simultaneous Monitoring
The use of cellular physiology to make target molecules has been practiced for centuries, with early examples being the production of wine and beer through yeast fermentation. Single (e.g., bacteria and yeast) and multicellular (plant or animal) organisms can be harnessed to produce otherwise chemically complex, low-yield, or chemically uncharacterized materials. These include “lock-and-key” receptor complexes with perfect stereochemical specificity, large-scale protein scaffolds, or antibiotics. One example is penicillin, with a sensitive β-lactam ring structure at its core (1). Mass-production…
Automated Closed-Loop Solution for Bioreactors and Fermentors
Today, there is much discussion regarding the promise of improved insight into bioprocess industry processes. Look to the pages of industry publications such as this one, and you’ll see that industry leaders in process measurement and control have begun to discuss openly the potential for simulating and modeling bioprocesses. “Important opportunities such as the application of mass spectrometers, dissolved carbon dioxide probes, and inferential measurements of metabolic processes have come to fruition today opening the door to more advanced process…
Carbohydrates and Their Analysis, Part Two
A polysaccharide is a complex glycan with at least 10 monosaccharide units. It can be formed by the multiples of the same monosaccharide (a homopolysaccharide) or by two or more monosaccharides combined (heteropolysaccharide). Two homopolysaccharides can have completely different conformations — and thus properties — based on the position and type of glycosidic linkages in the structure (Figure 9). Polyglucose ranges from cellulose — β(1,2,3,4) glucan, with its zig-zag chains regularly superimposed to each other and bound tightly by hundreds…
PAT Tools for Accelerated Process Development and Improvement
Broadley-James Corporation, Emerson Process Management, and the University of Texas at Austin are working together to examine and quantify the potential for faster optimization of batch operating points, process design, and cycle times. We’re also looking for more reproducible and predictable batch endpoints. The objective of this effort is to show that the impact of PAT can be maximized through the integration of dynamic simulation and multivariate analytics in a laboratory-optimized control system during product development. Data from bench-top and…
Bioassay Survey 2006–2007
Bioassays are required for a variety of purposes in the development and production of biopharmaceuticals including drug candidate selection, product releases, product stability assessment, and comparability to support proposed process changes. However, because of their complexity and susceptibility to many variables, bioassays often prove problematic and difficult to develop. Timely development of suitable assay systems represents a major investment on the part of the biopharmaceutical industry — but late development often results in even more costly clinical holds. PRODUCT FOCUS:…
A New Era for Bioprocess Design and Control, Part 2
The level or intensity of product and process understanding that can or should be achieved beyond the acceptable minimum level promises to be the scope of a continuing debate among biotech industry and its regulators. In practice, the path of increased understanding may follow a series of incremental steps toward the desired state (Figure 1) after a product launch. Realistically that is expected to occur when the level of product and process understanding has reached or slightly exceeded the minimum…
A New Era for Bioprocess Design and Control, Part 1
Elements of the biopharmaceutical industry’s new operating paradigm have inevitably created an immediate need to condense, interpret, and relate their implications to existing regulatory and industry practices. This also provides us with an opportunity to look at them in a broader context and in relationship to one another. Such a perspective may open up new directions in discussion on how design and control aspects of biopharmaceutical manufacturing are likely to evolve. These are exciting times for scientists, engineers, statisticians, quality…
The Biopharmaceutical Industry’s New Operating Paradigm
Currently the biopharmaceutical industry is transitioning to a new business model of production efficiency through implementing operational excellence (Op Ex). Borrowing from such principles as “lean manufacturing” and “Six Sigma” (6σ), and incorporating quality by design (QbD) (1), Op Ex is being applied through the implementation of such advanced enabling concepts and technologies as quality risk management (QRM) (2), process analytical technology (PAT) (3), and systems biology (SB) (4). Some people see a conflict here: This paradigm shift is occurring…