Plant expression systems are emerging as fast and inexpensive methods for producing vaccines. Someday, plants may surpass mammalian and even many microbial systems in efficiency and cost-benefits for the manufacture recombinant proteins. This is particularly so for the rapid manufacture of truly large-scale (million- or even billion-dose) vaccine antigens. Whether grown as single cells or tissues in photosynthesis reactors, as whole plants in controlled laboratory situations, or cultivated in fields of transformed food-commodity plants (e.g., rice, potatoes, or tobacco), plants being adapted for recombinant protein manufacture offer high yields and relatively low investment costs. These systems can move quickly from identification of a candidate to expression, testing, and manufacture.
According to our recent study, a wide variety of plant-based expression systems are being used for manufacturing products — often vaccines — currently in the development pipeline (
1
). Many cell culture processes are using...
For most biotechnology and biopharmaceutical organizations, “business as usual” means a perpetual race to the finish line: Conceive a new invention, reduce it to practice, attain patent protection, repeat ad infinitum. But sometimes, the very technologies scientists use to expedite that chain of events (e.g., electronic laboratory notebooks and cloud-based laboratory data sharing) create security and authenticity holes. In essence, the more agile and sophisticated our work flow systems become, the more difficult it becomes to guarantee the integrity of our underlying data. In today’s aggressively litigious climate, even the slightest, most theoretical potential for data inauthenticity is enough to invalidate years of arduous research and development.
Numerous documented cases of scientific intellectual property (IP) losses — either to competition or to public domain — have led to hundreds of millions of dollars in lost biotechnology and biopharmaceutical revenues, legal fees, and damages. It’s a complex p...
Biopreservation suppresses degradation and enables postpreservation recovery of structure, viability, and function. Although there are several biopreservation techniques (indicated in “Biopreservation Methods” box), most laboratories use either standard cryopreservation protocols (the far majority) or vitrification (much more limited in broad systems application) when freezing cells for research and clinical applications. Isopropanol freezing containers such as the Mr. Frosty device from Nalgene Labware have made cryopreservation easier in many applications, and controlled-rate freezers allow users to program and manipulate freezing rates.
Nonetheless, cryopreservation is not often given the same attention as other bioprocessing steps. I discussed these issues with Aby J. Mathew, a noted biopreservation expert and senior vice president and chief technology officer at BioLife Solutions. His opinion is that developers of cell therapy and regenerative medicine products often focus first on cell characterizat...
It’s always exciting to find out where the next meeting of the European Society for Animal Cell Technology will be. This venerable conference happens somewhere in Europe every other year. Recent sites have included Dublin, Ireland (2009); Dresden, Germany (2007); Harrogate, England (2005); Granada, Spain (2003); and Tylösand, Sweden (2001). This May, the gathering of animal cell culture scientists and engineers will convene in the palatial setting of the historic Hofburg Congress Center, formerly the Hapsburgs’ imperial residence in Vienna, Austria. ESACT meetings are famous for their beautiful locations and enjoyable social events. I for one will never forget the organized day outing at the magnificent Alhambra in Spain followed by a private classical guitar concert at the beautiful Huerta del Sello. But the biannual conference is far more than just an organized social event for industrial and academic cytologists from around the world.
The 1999 ESACT conference in Lugano, Switzerland featured Leonard Ha...
Because of the molecular complexity and relative fragility of biotherapeutics, validated intermediate hold times are critical for their commercial manufacture. Manufacturers typically conduct studies to define acceptable hold times for process intermediates to determine acceptable hold times for in-process production samples. A validation study defines maximum allowable hold times for all intermediate process stages based on product-specific data obtained during a hold study. A systematic risk assessment can determine which intermediate hold points should be validated (
1
).
Hold materials are typically obtained from production-scale batches and held at set temperatures and times. Time points are sampled periodically and assayed for product quality attributes (e.g., aggregates, fragments, oxidation, and acidic species) that may be affected by the hold period and for microbial control (e.g., bioburden and endotoxin) (
2
). Intermediate hold studies are often executed during large-scale manufacture of a bio...
Cosponsored by CASSS (an International Separation Science Society) and the US FDA, the 17th CMC Strategy Forum was designed to explore the relationships between higher-order molecular structure and quality of therapeutic proteins and peptides, vaccines, and blood-derived products. Understanding those relationships is important to defining and controlling the critical quality attributes (CQAs) of biopharmaceutical products. The forum program highlighted the current state of the art for analytical tools used to monitor higher-order structure. Case studies demonstrating the effects of changes to higher-order structure on biological function illustrated approaches to defining correlations. Presentations by experts from regulatory agencies, academia, and industry were followed by discussions focused on correlating data derived from analytical tools to biological functions of molecules. A predefined set of questions helped focus the discussions (see “Structure of the Forum”).
PRODUCT FOCUS: PROTEIN BIOLOGICS
PR...
+3During biopharmaceutical manufacturing, final drug products can get contaminated with host-cell proteins (HCPs) derived from a production cell line. HCPs can elicit adverse immune responses, so regulatory authorities require accurate monitoring of their presence and concentration in final drug products. Because they are robust and offer good throughput, enzyme-linked immunosorbent assays (ELISAs) are the first choice for HCP detection to monitor product quality. Generic ELISA kits are commercially available for HCP detection with a number of commonly used biopharmaceutical production cell lines. Use of such kits could obviate the necessity of generating new HCP-reactive antibodies for each new manufacturing process. Although use of a universal kit could save time and money, universal HCP reactive antibodies may not adequately react with all HCPs potentially present in every biopharmaceutical product and unique process.
PRODUCT FOCUS: PROTEINBIOLOGICS
PROCESS FOCUS: MANUFACTURING
WHO SHOULD READ: PRODUCT A...
+5 The biotechnology industry is continually looking for new methods of improving titer of biotherapeutic proteins. Numerous reports show that nutrient supplementation improves productivity several-fold (
1
,
2
). Maintaining cells in a viable and productive condition is the ultimate goal and generally involves adding small volumes of concentrated nutrients to cell cultures. Important parameters for designing a nutrient supplement include ease of use, operator and site safety, and product storage footprint at a manufacturing facility. Traditionally, these supplements come as concentrated liquids, which can present logistic issues when large quantities of liquid must be shipped to and stored at a manufacturing site. In addition, highly concentrated components may cause precipitates to form in storage containers during long-term storage.
Dry-format nutrient supplements (e.g., milled powders) minimize many shipping and storage problems but may have other issues, including extended mixing times for complete solu...
As cell line development and engineering mature, this industry faces new challenges and new lines of questioning. Where is the need for innovation? What enabling technologies will provide which companies with advantages over their competition? How can we leverage continued improvements to increase the speed of clinical and manufacturing facilities? How much can we improve understanding and development by applying “CHO-omics” and highthroughput systems? Do we have the tools to process and analyze all the available data? As biosimilars gain momentum, how will they change the landscape of this industry?
Developed by your peers, IBC’s 7th Annual Cell Line Development and Engineering conference provides a forum to answer those questions and bring companies of all sizes closer to their ultimate goal of increasing efficiency and speed of development while reducing costs and resources and optimizing their processes. By joining us, you will hear industry experts and world-renowned academics share lessons learned a...
Technical Services
Service:
Pall Scientific and Laboratory Services (SLS) group
Applications:
Downstream processing
Features:
Established >40 years ago, Pall’s SLS group employs experts in chromatography, viral clearance, liquid and air filtration, microbiological process monitoring, tangential-flow and depth filtration, and blood processing. Services offered include validation, consulting, process development and proteomics, preinspection reviews, contamination analysis, and training. Instrument services include calibration, servicing, upgrades, documentation, qualification and technical support.
Contact Pall Life Sciences
www.pall.com
Spectrophotometry
Product:
Evolution 200 series
Applications:
QA/QC analyses
Features:
Thermo Fisher’s Evolution 200 series of UV–visible spectrophotometers features Insight software with customized user
–
environment scripting capability. Designed for routine quality testing and standard quantitative analysis, three instruments offer fast data collection for kinetic...
The cell therapy industry’s biggest challenge is in manufacturing. Technologies are needed to support expansion of large numbers of cells for commercial production. A number of sources are presenting options: e.g., standard two-dimensional tissue cultures that “grow up” to Corning HYPERFlask and CellSTACK or Nunc Cell Factory systems; hollow-fiber–based equipment; and disposable bags and traditional stirred-tank bioreactors. Each has its place and application, but how can companies choose among them? Where and when do they initiate scale-up process development with limited resources and intense focus on clinical demonstration of therapeutic benefits?
The simplest way to move forward is scaling
out
rather than
up
. During lean and dry years, this might indeed be the best approach. It can take a company through clinical trials with minimal scale-up efforts, mainly related to fluid transfer and plastic handling. But lot-size limitations and associated costs in labor, cleanroom footprint, and incubator spa...
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