This issue marks the beginning of BPI’s tenth volume of publication. We debated how and when to launch our tenth-anniversary year: Issue 1(1) was published in January 2003, but the magazine was actually “born” in mid-2002 with its adoption by Informa. We founding editors had six months in our 400-ft
2
Eugene, OR, office to build an acquisitions database, create a manuscript pipeline, and design the magazine’s first templates. (A radical idea: BPI was designed by editors, who still create all layouts and article-related graphics). Meanwhile, our publisher and first sales representative were creating the business operations and managing early qualification of our readership at the Informa office in Westborough, MA. In one of the most creative periods I’ve ever experienced, we thrived on close editorial and sales relationships that have characterized our operations ever since.
Before settling on a real name for the magazine, we called it “Bio-X,” a play on the “GXP” label for good regulatory practices. So o...
Disposables:
Single-use technology has arguably been the biggest “story” of the past 10 years in bioprocessing. And for many people, implementation of disposable elements began soon after the turn of the century with a Wave bioreactor (
1
,
2
), first developed by Wave Biotech in 1996, now a mainstay of many an upstream process development laboratory and sold by GE Healthcare. BPI identified the significance of such technologies early on, making them the subject of a supplement in its second year. By the fourth installment of what became an annual tradition, there were even more disposable bioreactor options available than I could pack into an overview article (
3
), as I heard from a few readers after it was published. A 2009 update by two Swiss academics narrowed down the field to two main categories: static and dynamic bioreactors (
4
). Among the latter, mechanically driven (rotating, shaken, stirred, and wave-mixed) options outnumber the pneumatically or hydraulically mixed options, and hybrid syste...
When you think of futuristic manufacturing facilities and processes, robots might come to mind in a science fiction setting where humans are absent and production lines are directed by computerized drones that perform tasks we can’t even imagine today. As the pace of technology shuttles us swiftly into the real future, however, life-science manufacturers need to pause to examine the purpose of automation and how we can best steer its course.
In bioprocess manufacturing and other industries, technology is growing more powerful and sophisticated for solving problems. General users and implementers of new technologies, however, don’t fully tap into available technology capabilities that exist. Sometimes the complexity overwhelms manufacturing teams and (because of layoffs and consolidation) information technology (IT) departments’ available time. So the options are outpacing the industry’s ability to understand and correctly apply technological solutions to its manufacturing challenges.
Despite advancing tec...
Since the late 1980s, studies have shown that plants can manufacture functional transgenic pharmaceutical compounds. Advantages attributed to plant-made pharmaceutical (PMP) approaches are compelling, and PMP production continues to attract interest from investors and the biopharmaceutical industry (Table 1). Proposed PMP benefits include proven scalability, high production capacity, limited exposure to human or animal pathogens, lower capital expenditures (CapEx), and decreased operating costs. Those putative advantages have proven to be significant business forces driving continued investor support for PMP ventures. PMP production’s lower cost relative to cell culture provides an opportunity to subsidize more research for additional product development.
Table 1: PMPs in clinical trials as of March 2010*
Placed in wider context, the business value, for example, of potentially large production capacity coupled to lower CapEx requirements and manufacturing costs is underscored by concerns over the expandin...
+3Cells and cell-derived reagents form the basis of an operationally challenging class of test methods used in execution of product potency testing (stability and lot release), assessments of pharmacokinetic/ pharmacodynamic (PK/PD) profiles, detection of antidrug antibodies (ADAs) or neutralizing antibodies (NAB), and characterization and comparability testing of biopharmaceutical products. Frequently, cell-based assays provide the only measurement of the tertiary/quaternary structure of each batch of product at the time of lot release and during stability testing to assist in determining product shelf-life. Cultured cells themselves are often used to generate monoclonal antibodies (MAbs), enzymes, or substrates for use as critical reagents in other types of tests, including ligand binding and enzymatic assays. In all these applications, the cells serve as highly critical, highly complex “reagents” that require distinct characterization and control measures to ensure operational consistency over time.
Cell...
+3 Metabolic process engineering (MPE) was developed at Bristol-Myers Squibb Company as a tool to effectively control and optimize industrial cell culture processes used for production of biological drugs. A fundamental need was identified to introduce manipulations to the metabolism of production cell lines without genetic engineering. Optimization goals for production cell line performance include, for example, volumetric productivity, control of product quality attributes and by-product formation, and improved process scalability. With MPE, we could achieve targeted changes to cellular metabolism through timed addition of chemicals to a production process.
Here we describe the MPE concept and provide examples of its use. We made two further observations when applying it: Well-understood, scientifically based changes to the production process had the highest chance of meeting product comparability needs, thus facilitating regulatory approval. And poorly understood, empirical approaches carried the risk of ...
In process development, appropriate scaling is important to achieve acceptable product quality without compromising titer (
1
). Scale-down approaches involve matching the oxygen transfer coefficient (
k
L
a
) value, impeller tip speed, power per unit volume, or mixing time to those of a bioreactor (
2
). Bench-top bioreactors are typically used in bioprocess engineering as scale-down models of commercial units in fermentation and cell culture because of their similarity in geometry (
H
/
D
ratio) and mechanical properties (agitation type and sparging). By contrast, shaking culture systems such as Wave bioreactor (GE Healthcare), shake flasks, and tube spins are typically used for culture expansion.
Significant improvements to the composition, shape, size, and caps of shake flasks have facilitated sufficient oxygen transfer and mixing (
3
). Such modifications have allowed for use of shake flasks in production cultures for clone evaluation, media development, and process optimization. But discrepancies i...
+3 Recombinant DNA (rDNA) technologies provide a wide range of tools for producing a broad array of recombinant proteins. Since the early 1970s, the biotechnology industry has harnessed those tools — together with genetic engineering and genomics — for developing new classes of innovative and effective therapeutic molecules. The therapeutic recombinant protein market segment now represents the core of the medical biotechnology industry, with hundreds of companies involved in discovery, development, and marketing.
Although recombinant technologies are extremely powerful tools, significant limitations in expression, upstream, and downstream processes still exist for many proteins that have therapeutic potential. Failure to obtain specific product features such as posttranslational modifications and high yields jeopardize the probability of developing relevant proteins into approved therapeutic drugs. The need for technologies that allow reliable and effective therapeutic protein production capabilities is grow...
+5 Disposable Bioreactor
Product:
UniVessel SU controller
Applications:
R&D and process laboratory-scale cell culture
Features:
UniVessel SU bioreactors work with most Sartorius Stedim BIOSTAT benchtop controllers as well as those for conventional, stirred-tank glass bioreactors. The system includes disposable SENSOLUX sensor patches for optical noninvasive pH and dissolved oxygen (DO) measurement. It is applicable to small-scale protein expression, media, and process optimization studies.
Contact
Sartorius Stedim Biotech SA
www.sartorius-stedim.com
GMP-Grade Nutrient
Product:
CGMP-grade hyaluronic acid
Applications:
Cell culture, drug delivery, and medical devices
Features:
Novozymes debuted CGMP-grade hyaluronic acid (HA) derived from
Bacillus
culture at CPhI Worldwide 2011. Produced at a new facility in Tianjin, China, designed exclusively for its production, this HA is derived from a patented water-based process run in compliance with ICH Q7 guidelines. It is free of animal-derived components a...
A recent study published by CAPS Research (the research arm of the Institute of Supply Management), underscores the importance of organizations adopting external innovation rather than relying solely on their internal research and development (R&D) efforts. Some companies set goals to increase revenues by adopting external innovation. Procter & Gamble, for instance, wanted to attain 50% of its revenues through external innovations — that is, licensing technologies — over five years (
1
).
A joint project from CAPS Research with Western Michigan University and Arizona State University,
Innovation Sourcing: Contributing to Company Competitiveness
was published in March 2011 (
2
). Its findings are supported by the seventh annual global survey of senior executives conducted by The Boston Consulting Group in conjunction with
Bloomberg Businessweek
(
3
). Three significant findings of the former stand out:
Other People’s Intellectual Property
Another factor that influences the acceptance of external innova...
Scale-up a stem cell process may be challenging: small variations in physicochemical parameters (surface characteristics, pH and dissolved oxygen) can heavily impact stem cell growth and behavior.
The Integrity® Xpansion™ multiplate bioreactors have been designed to enable an easy transfer from multiple-tray stacks process by offering the same cell growth environment: stacked hydrophylized polystyrene plates in a compact and closed system (from 10 to 200 plates per bioreactor equivalent respectively to 6120cm² and 122400cm²). As there is no headspace between plates, gas regulation occurs via silicon tubing placed in a central column, enabling the regulation of the critical cell culture parameters (pH and dissolved oxygen).
Hepatic progenitor stem cell process in multilayer trays has been successfully transposed in less than 6 months into the Xpansion bioreactor, without losing the cell therapeutic potency. First cultures were performed in Xpansion 10 plates allowing to define optimal cell culture paramete...
