Welcome to 2011 — and our ninth year of publication. This milestone is both rewarding and a bit daunting. We want to
drive
discussions rather than just reveal their results. Venturing into new territories can require more than a simple roadmap. Think of bioengineers as experienced “cooks” who have reached a confidence level allowing them to combine recipes and create new “menus” from existing processes. Same ingredients, different combinations — with tasty new chemistries. But what do you call the results?
In BPI’s first couple years, we published an occasional series of “Defining Moments” on our final page. Advisors and authors often expressed frustration at misapplied terms: e.g.,
bioassays
and
assays, bioanalysis
and
analysis
. Beyond simple differences in perspective are two important reasons to get all this “right.” Have you ever compared the results of seemingly similar industry surveys and wondered why their numbers were so confusingly different? One reason may be operative definitions in th...
When a company is involved in litigation, the court in which its case is heard can have a significant impact on the proceedings. For life-science corporations, this is especially true. Because their products are often distributed to consumers across the United States and the world, such companies can benefit from the consistency and efficiency provided by federal courts. Federal courts provide uniform procedures across the United States, have mechanisms for consolidating similar claims across state lines, and are generally preferred by corporate defendants. Until recently, though, it has not been entirely clear when a company operating in multiple states has access to such courts.
In light of a recent US Supreme Court decision in
Hertz Corporation v. Friend
, however, it is now much easier to answer that question (
1
). Under that ruling, corporations will know and can control when federal courts will be available, providing greater certainty in litigation. Except for lawsuits brought within a corporatio...
Development, testing, review, approval, and marketing of biosimilar drugs in the United States presents unique safety and regulatory challenges (
1
). By contrast with traditional small-molecule drugs, biologics derive from sources such as genetically engineered cell lines, plasma, and tissue specimens (
2
,
3
). Patents on first-generation biologics approved and marketed in the United States have begun to expire, thereby opening the market to less-expensive “generic” versions. The complexity of biologic drugs and the specificity of their source materials, however, make it impossible for such follow-on products to be exactly the same as their brand-name predecessors; thus, they cannot rightfully be considered generics (
1
,
3
). Because of their complex nature and size, biologics also tend to be more immunogenic than traditional small-molecule drugs. Although the immunologic reactions that most biologic drugs trigger tend to be relatively harmless, there have been cases in which the unexpected immunogenic...
+1To ensure product safety and efficacy, protein therapeutics must meet defined quality characteristics immediately after manufacture as well at the end of their designated shelf lives. Many physical and chemical factors can affect the quality and stability of biopharmaceutical products, particularly after long-term storage in a container–closure system likely to be subject to variations in temperature, light, and agitation with shipping and handling. Compared with traditional chemical pharmaceuticals, proteins are considerably larger molecular entities with inherent physiochemical complexities, from their primary amino acid sequences through higher-order secondary and tertiary structures — and in some cases, quaternary elements such as subunit associations (
1
).
Many proteins are glycosylated, and some have other posttranslational modifications such as phosphorylation, which also affects their potential degradation pathways as well as the kinetics of their degradation. Proteins are typically sensitive to ...
+3 Most biopharmaceutical processes involve purifying proteins and peptides from various sources. Typically, purification schemes contain multiple unit operations, including several chromatographic steps to ensure safe removal of critical impurities and contaminants. Each step affects the overall process economy by increasing operational cost and process time and by causing product losses.
Carefully designing a purification procedure to reduce the number of steps is an efficient way to reach high process economy. Expanded-bed adsorption (EBA) technology is a powerful alternative to conventional clarification techniques. It can improve process economy while increasing process robustness and yields.
Increasing Robustness
A client requested help on improving a process that had been used to produce a chimeric Fab fragment (Fab effector molecule) in
Escherichia coli
for phase 2 trials. The process did not have the required robustness for phase 3 studies because product yields unacceptably fluctuated between 50 ...
Single-use (SU) components are widely accepted in bioprocessing due in part to improvements in component design, a wider range of products, and increased scalability. Benefits driving their increased use include elimination of cleaning, improved system flexibility, and reduced risk of contamination.
Nonetheless, companies now question how far disposables can be incorporated into bioprocessing unit operations. Results of the second annual survey of the bioprocessing market fo single-use solutions showed that >90% of respondents considered filtration well suited for single-use processing, compared with 54.5% for chromatography and only 24.2% for centrifugation. Nearly 72% of survey participants indicated the purification applications they would be most interested in using in a single-use approach was tangential flow filtration (TFF). Applications incorporating TFF, in part or fully, also gained high scores (59.3% for diafiltration and 65.6% for concentration).
PRODUCT FOCUS: ALL BIOLOGICS
PROCESS FOCUS: DOW...
Of the available on-line biomass assay types, radio-frequency impedance spectroscopy (RFI, often referred to as
capacitance
) is generally regarded as the most robust and reliable method for monitoring viable biomass during fermentation and cell culture. The first article to show that capacitance could be used to estimate microbial biomass dates back over 20 years (
1
). Today the technology is routinely used for monitoring and controlling mammalian cell culture processes and high-density yeast and bacterial fermentations in research, process development, and manufacturing applications. Capacitance assays have proven to be robust and easy to scale up. Furthermore, capacitance measurements are insensitive to gas bubbles or debris with cells either in suspension or attached to inert carriers (
2
).
The advent of disposable bioreactors has led many biopharmaceutical companies to switch from conventional glass or stainless steel vessels to single-use alternatives. Some on-line probes can be provided with dis...
Laboratory Automation
Product:
Octet platform
Applications:
Label-free molecular binding analysis
Features:
ForteBio chose Hudson Robotics to provide automation capability for its Octet biolayer interferometry analytical instruments. The platform includes Dip and Read biosensors, reagents, and assay kits for analyzing biomolecular interactions in 96-and 384-well microplates. The two companies developed out-of-the-box, integrated automation for Octet QK384 and RED384 systems with Hudson’s PlateCrane EX robotic arm and Micro10x robotic reagent dispenser. A bar-code scanner reads and records microplate bar-codes for SoftLinx interface control
Contact Hudson Robotics, Inc.
www.hudsonrobotics.com
Contact ForteBio, Inc.
www.fortebio.com
Disposable Bioreactor
Product:
CelliGen BLU bioreactor
Applications:
Batch, fed-batch, or continuous animal cell culture in research or production
Features:
New Brunswick’s disposable bioreactor is based on a traditional stirred-tank design. It was engineered for high-dens...
IBC’s Antibody Development and Production conference offers the latest technical and scientific advances in bioprocessing to help companies of all sizes improve speed, quality, and cost in developing and producing antibodies. Exclusive case studies deliver the latest data together with strategic discussion forums that allow the industry’s leading scientists, engineers, and executives to collaborate and find solutions to their most pressing challenges.
Gain from companies sharing “lessons learned” from their own experiences developing and optimizing processes and production of antibody-based therapeutics:
Keynotes
“Antibodies: Successes, Failures, and What’s Next?” by Marian T. Nakada (vice president of biotechnology strategy, operations, and external innovation at J&J Pharmaceuticals’ Biotechnology Center of Excellence)
“Defining and Demonstrating Suitable Product Quality Over the Course of Development” by Reed Harris (senior director of analytical development and quality control at Genentech, Inc.)
“Bios...
Quality by design (QbD) was a hot topic at IBC’s
BioProcess International
Conference and Exhibition, 20–24 September 2010 (Providence, RI). For her keynote address, Helen Winkle (director of the FDA’s Office of Pharmaceutical Science) discussed the agency’s continuing efforts to improve product quality regulation as well as opportunities and challenges of implementing QbD for biotechnology products (
1
). Since introducing its 21st Century Initiative in 2002, the FDA has made some headway toward enhancing product quality through QbD (
2
). The QbD pilot program originally designed for small-molecule drugs has been extended to biotechnology products. However, according to a recent McKinsey & Company study summarized by Ms. Winkle, there is significant confusion and disagreement within the agency over how QbD should be applied to biotechnology products and what type of data should be required to define a biotechnology design space.
The study reports that QbD implementaion is being hindered by a lack of ta...
+1 
