March 2008

Taking the Next Step

Long-term hopes for stem cells to cure various diseases are nourished by the latest developments in stem cell research. First clinical studies have begun (Thera Vitae, Israel: congestive heart insufficiency), and patents have been filed (Stem Cell Therapeutics, Canada: combined regulation for the production of neural cells). Clinical use depends on technological requirements for a reproducible cultivation and controlled differentiation of cells in sufficient numbers, so more and more researchers are focusing on the scale-up of stem cell production. For…

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:…

Appendix 1: Designing for Process Robustness

A rich cup of coffee is what comes to mind for many people when you mention the word robust. For biotechnologists it is often a comfortable term, generally referring to the overall strength or ruggedness of a manufacturing process. However, the origin of the robustness concept for manufacturing is found in the field of robust design, which has for decades been a rigorous discipline with its own metrics, algorithms, and mathematical tools. Lately it has experienced a renewed interest in…

Cell Cultivation Process Transfer and Scale-Up

The introduction of therapeutic monoclonal antibodies (MAbs) has greatly revolutionized therapies for several cancer immune disorders (1,2,3,4,5). Benefits to patients have been substantial, translating into both increased life expectancy and improved quality of life. Currently, twenty-one therapeutic MAbs are registered for marketing in the United States, with the introduction of several more expected in the coming years (6,7,8,9,10,11). PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: Technology transfer (production) and analytical methods developmentWHO SHOULD READ: PRODUCTION AND PROCESS DEVELOPMENT, MANUFACTURINGKEYWORDS: IGF-1R, EXPRESSION, TECH…

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…

Shared Risk

Risk is inversely proportional to one’s distance from a problem. For regulators, it seems straightforward to control biopharmaceutical and medical device risk. For pharmaceutical, biotechnology, and medical device executives, however, risk is hardly so clearly defined; it extends, grows, twists, and compounds through a chain of suppliers, consultants, and business partners. So when regulatory officials claim that compliance accountability cannot be delegated, biopharmaceutical and medical device companies are left holding the bag. Years ago, as a C-level executive for a…