Cell culture automation has become more common in drug discovery and research applications, thereby freeing bench scientists from repetitive work as well as improving the consistency of their cell culture processes (
1
). Mammalian cell culture is used in the production of biopharmaceuticals, where developing a production cell line requires a large amount of repetitive manual work for bench scientists. With the increasing importance of biologics in today’s pharmaceutical market, throughput and efficiency are crucial in developing a production cell line. Identifying ways to automate parts of the process can increase throughput, efficiency, and consistency.
Cell culture automation for bioprocess development is an expensive investment, and many factors should be carefully considered before a company commits to a purchase. First, the work process should be clearly defined to justify the purchase. A company should also identify the time-consuming and repetitive steps of its process that would benefit from auto...
Significant changes are being incorporated into biopharmaceutical manufacturing processes as a result of drivers such as increasingly strict regulatory demands, reduction of manufacturing costs, and outsourcing to contract manufacturing organizations (CMOs). Historically, many biopharmaceutical processes were designed and built based on cleanable, reusable stainless steel systems and unit operations. Today several industry drivers are shifting some unit operations toward single-use technologies, namely lowered cross-contamination, reduced capital investments, and desired further reduction in manufacturing costs and shortened drug development times (
1
,
2
,
3
).
The general benefits of disposable systems have been described in various case studies and technical articles (
4
,
5
,
6
,
7
,
8
,
9
), but their suitability for each specific process must be assessed individually. One universal requirement, whether a system is single-use or reusable, is the application of good engineering practices and the effec...
Biopharmaceutials and the processes used to make them are exceedingly complex, and the path to developing new therapeutics is a high-risk endeavor. The emphasis today is on controlling product quality, safety, and efficacy through understanding biological mechanisms, key product attributes, and process parameters. Such information is also crucial for guiding development efforts to improve chances of success in the clinic and for gaining regulatory approval. Analytical methods provide the foundation for acquiring such knowledge. Efforts devoted to developing meaningful and reliable analytical methods early in development will pay huge dividends and can make the difference between success and failure.
Drug development is a tough business. Costs are astronomical, and the odds of failure are about nine out of 10 for every new drug that enters clinical trials. Current estimates for bringing a new drug to market are over US$1 billion spent on an average timeline of 12–15 years. High development costs and the li...
As the Chinese calendar warned us, it did indeed turn out to be a year of the rat. If you‘re in any doubt about the economic crisis of 2008, here’s a single significant indicator: Pharmaceutical companies’ spending on advertising
declined
this year for the first time in history. Walgreen’s CEO Jeffrey Rein was quoted in
FierceBiotech
as calling 2008 “the tightest market for prescription drugs” in his 27-year career.
If big pharma
and
big retail were feeling the pain, of course the average citizen was too. According to a September
Wall Street Journal
article, consumers began cutting their health spending as the slowing economy took its toll. During the first quarter of 2008, the number of prescriptions filled in the United States fell by 0.5% — and by 1.97% during the second quarter compared with the same quarters of 2007. Those were the first negative quarters in more than a decade, according to IMS Health.
A Year of Less Health Care:
In a survey by the National Association of Insurance Commissio...
+1Development of industrial cell culture processes for production of recombinant proteins seeks high efficiency, reproducibility, and predictability. Usually the time allowed for process development is short, during which culture conditions and scale-up protocols must be defined so as to maximize cell productivity and yield while minimizing process scope and overall costs (
1
).
Although scientific literature describes various methods that increase productivity of a cell culture by reducing and arresting cell growth or weakening cell physiology (
2
), the cells must be in good physiological state at the beginning of each process so that long and costly preproduction scale-up steps will be unnecessary. Furthermore, those in a poor physiological state may respond unfavorably to stresses occurring in industrial-scale bioreactors, which emphasizes the central role of cell physiology in successful process development (
1
).
PRODUCT FOCUS:
ALL BIOLOGICS
PROCESS FOCUS:
PRODUCTION
WHO SHOULD READ:
QA/QC, PROCESS...
+7 Autologous chondrocyte transplantation is a modern experimental therapy for treatment of degenerative intervertebral disc diseases. Several studies with animal models have shown that transplantation of cultivated autologous chondrocytes can delay progression of disc degeneration. A few products based on human autologous chondrocytes are already on the market. Repair of disc damages with grafted chondrocytes appears feasible in the near future. So chances are growing for clinical applications meant for restoration of original disc function. As a result, optimization and standardization of the individual steps of the laborious therapeutic approach gain even more importance.
Apart from minimally invasive treatments for removal of chondrocytes and later retransplantation, the laboratory process requires a long cultivation period under in vitro conditions. Successful proliferation of each patient’s own chondrocytes is the main focus. Ideally suited for this approach is a standardized cell culture with highly r...
Problems associated with affinity purification in antibody production continue to increase as upstream cell culture expression levels improve. As a result, many vendors and users in the biopharmaceutical industry are working to identify alternative technologies that can replace tried-and-true column chromatography.
In the fifth annual report and survey by BioPlan Associates, 434 global respondents pointed to bottlenecks created by downstream processes as one of their most serious manufacturing problems today (
1
). Amost two-thirds (63.8%) said their facility is experiencing some degree of bottleneck. This problem has been growing over the past five years.
Problem Areas
Respondents identified 14 different areas in which their facilities face significant downstream production problems. The top area, noted by nearly 47%, was column chromatography. That was followed by process optimization (33.1%) and validation (28.3%). To produce greater quantities of biologics in existing operations, companies need to rem...
IBC’s Antibody Development and Production conference will help you evaluate the latest scientific and technical approaches to successfully accelerate the development of robust processes. This event is regarded by the industry as the most comprehensive event that brings you best practices across the spectrum, including the most critical stages of upstream and downstream processing.
Keynote Presentations
“How Do We Get to 30 g/L Using Fed-Batch Technology? What Are the Limitations?” by
Thomas Ryll,
director of cell culture development at Biogen Idec: Production of antibody drugs using mammalian cell culture has made significant progress over the past 20 years. Typical titers are nowadays in the 2–5 g/L range, with reports more recently in the 10 g/L range. The presentation will discuss some limitations involved with standard fed-batch process realization in typical manufacturing facilities. Case studies of intensifying such processes at Biogen Idec show how limitations to titer and volumetric productivity...
Disposable Bags
Product:
Bioprocessing bags
Applications:
Containment, mixing, and so on
Features:
Flexel 3D standard bags are designed for processing, storage, and transport of large-volume biopharmaceutical solutions. These disposable bags fit Sartorius Stedim Biotech’s Palletank containers or commonly available plastic drums. The bags provide a single-use alternative to traditional stainless-steel vessels in a range of applications. Standard Flexel 3D bags come as sterilized and ready-to-use stand-alone bags or filter-and-bag assemblies that incorporate a range of tubing, connections, filters, and bag sizes (50–1,000 L). Many designs incorporate C-Flex TPE tubing, allowing the use of BioWelder and BioSealer sterile connection and disconnection devices.
Contact: Sartorius-Stedim Biotech
www.sartorius-stedim.com
Refrigeration, Incubation
Product:
Innova 42 and 42R incubator shakers
Applications:
Cell culture, fermentation, and molecular biology
Features:
New Brunswick Scientific has introduced tw...
Major efforts are under way to develop new, high-efficiency, cell-based expression systems and flexible low-cost biomanufacturing platforms for biotherapeutics and vaccines to drastically reduce development and manufacturing times. The industry’s enormous growth is driving many of these efforts. The global market for biotherapeutics now stands at $80 billion. Resurgent interest in vaccines is coupled with recent failures in current vaccine manufacturing technologies and the advent of cell-based vaccine manufacturing. The emerging class of follow-on biologics will create additional demand for new, cost-efficient manufacturing platforms.
Less visibly, government has become a driver of new biomanufacturing technology as well. Many governments now recognize that manufacturing systems that can be deployed rapidly and flexibly are integral to responding to pandemic or biological threats. Current vaccine and protein manufacturing systems have a number of limitations that represent significant biodefense vulnerab...
