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Recently in Washington, DC, two conferences were held on the topics of cell and gene therapy. The California Separation Science Society (CASSS, www.casss.org ) hosted a Well-Characterized Biological Products (WCBP) Chemicals, Materials, and Controls (CMC) strategy forum on “Current Practices for Assessing the Comparability and Stability of Gene Therapy Products,” while blocks away, Phacilitate hosted the 2008 Cell and Gene Therapy forum. At the WCBP CMC strategy forum, participants heard the US FDA–CBER perspective on the importance of comparability studies for gene therapy products. Denise Gavin discussed the available guidance and references for such products, then outlined in more detail the purpose and importance of comparability studies in the field along with methods for demonstrating comparability. J. Fraser Wright, scientific director of the clinical vector core in the Center for Cellular and Molecular Therapeutics at the Children’s Hospital of Philadelphia, PA, presented a case study assessing c...
This event offers key strategic insights from industry leaders regarding assay qualification and validation optimization, improvement of the pace and quality of analytical results, and improvement of product quality through increased process understanding. It brings together three conference programs including The 4th Annual Analytical Method Validation, the 2nd Annual Biophysical Analysis for Bioprocessing, and IBC’s 5th Annual Process Quality Forum on Process Characterization and Control. Analytical Method Validation This event gives assay development and validation scientists a broad view of how qualification and validation activities are performed across the industry. Learn about timing and resource allocation at each step, receive updates on key regulatory and standards initiatives, and learn how to optimize your method transfers. Analytical Keynotes “Interdependence of Product Characterization, Analytical Method Validation, and Comparability Assessment” by Chulani Karunatilake, PhD, director of a...
Process Monitoring Product: SciLog conductivity, pressure, and temperature (pictured) sensors Applications: In-line single-use purification monitoring Features: Sensors come with embedded memory with stored IDs, serial numbers, lot numbers, calibration, and any calibration offsets. Products are cleanable with NaOH or sterilizable by autoclaving, ethylene oxide, or gamma irradiation. Sensors and monitors document parameter changes during processing and send them to a printer, programmable logic controller (PLC), or to a spreadsheet on a personal computer. They come in a variety of sizes and configurations, patents pending. Contact SciLog, Inc. www.scilog.com Cell Culture Product: 19.5-L and 40-L sterilizable-in-place benchtop or mobile bioreactor Applications: Pilot- and production-scale cell culture Features: This modular system is designed to provide flexibility to meet changing process requirements, at any time, pre- or postdelivery. It includes options for gas flow, impellers, probes, spray bal...
As biosimilars move into the forefront of consciousness in the biopharmaceutical industry, analytical methods, especially comparability studies, have an increasingly important role to play. Additionally, as more products progress from phase 1 to 2–3 studies and require production-scale manufacturing, analytical methods are an important component of technology transfer or in-house scale-up efforts. The Analytical Methods for Biologics track will elucidate these challenges, and will include discussions about the latest changes in immunogenicity guidance, posttranslational modifications, analytical strategies, comparability testing, and bioassay development. Robin Thorpe , head of the biotherapeutics group at the National Institute for Biological Standards and Control, and a member of the EMEA drafting group, will start off the presentations with a review of the EMEA draft guidance, Immunogenicity Assessment of Biotechnology–Derived Therapeutic Proteins . Nadine Ritter , senior consultant with the Biologics...
Record-breaking titer outputs in mammalian cell culture systems in the past few years have pushed the industry to a new crisis of sorts: resolving the downstream bottleneck. However, the cell culture and fermentation groups at biopharmaceutical companies aren’t yet ready to sit back and rest on their laurels. Instead, they are moving forward, tackling the downstream issue with upstream modifications and continuing their drive for more cost-efficient processing. The Cell Culture and Upstream Processing track will focus on cell culture media development, clone selection, cell line engineering, alternative expression systems, scale-up strategies, and streamlining process development and optimization. Nicole Borth , professor in the department of biology at the Institute of Applied Microbiology in Vienna, Austria, will speak about the benefits of flow cytometry and cell sorting in improving understanding of cellular performance. “Flow cytometry is based on measuring the fluorescent properties of single cells ...
In 2006 a new term was coined that is now all too familiar in the industry: downstream bottleneck . With observations of a slow cycle of downstream process improvements indicating potential solutions in the next five years, downstream processing is a very hot topic at conferences and in publications. Thus, the Recovery and Purification track will be highly focused on this pertinent and timely issue. Beyond discussing the bottleneck itself head-on in the opening sessions, the track will focus on alternatives to protein A purification and conventional chromatography, benefits of single-use technologies, optimization strategies, and enhanced downstream process development methods. Joe Zhou , scientific director of process development at Amgen, will analyze single-use systems in downstream processing. He will look specifically at the use of single-use depth filtration, membrane chromatography, and nanometer filtration technology products for MAb processing. In an interview with BioProcess International , Zh...
Small molecules are still not providing cures for many diseases, and this is why biological therapies continue to be developed. They often offer greater convenience to patients, as well as longer lasting therapies,” says William Prather, MD, senior vice president of corporate development at the Israeli stem cell company, Pluristem. The therapeutics area at this year’s BIO International Convention will play host to many interesting technologies for producing and improving protein therapeutics, vaccines, and stem cells. Protein Therapies Remain Top Dog With an estimated market value in excess of US$57 billion in 2006 and a growth rate of 12% until 2010 ( 1 ), it’s not hard to see why companies are still very active in protein therapeutics. One driver of this market (encompassing monoclonal antibodies, proteins and peptides) is the increasing need to produce safer protein therapies. Jeff Cleland, vice president of therapeutic development at Barofold and a speaker at the BIO convention this year, states: “The...
The final hurdle in getting a product to market is the formulation and fill–finish step in process development. By their nature, protein therapeutics are more fragile and require a great deal of work to achieve product stability in final formulations. A cell line can be highly productive and efficient in protein production, but if you can’t stabilize the resulting protein and deliver it to patients intact, that’s a costly and useless exercise. The Formulation and Drug Delivery track of the conference will focus on the problems that have been identified in the industry and help attendees who work in this area of the process development cycle to solve problems they may experience. The track will focus specifically on stability testing, high-concentration and novel formulations, protein aggregation, and new developments in delivery. Mary Cromwell , senior scientist at Genentech, will speak about opalescence in formulation. Cromwell explained that this phenomenon is common in formulation science, and she will...
When you hear the phrase “laboratory analysis” on a TV commercial, maybe you imagine a technician in a white coat and safety goggles pouring a chemical from one test tube to another. Technicians still wear white coats and goggles, but today, in many labs, they’re not the ones pouring the chemicals. Instead, tiny trays carrying minuscule dabs of samples are whisked by robots from one analytical workstation to another. The workstations are equipped with ultraprecise instrument systems to prepare the plates, apply dyes, dispense reagents, mix whatever needs mixing, incubate cells, maintain temperature controls, apply UV light or chromatography or spectroscopy or X-rays, and measure and record reactions — thousands of them in an hour. The whole operation is governed by a PC on the laboratory bench, which tells the workstations and robots how to conduct the testing and tracks the experiment’s progress from start to finish. Laboratory automation offers scientists “the ability to set up large sequences of experi...
Because the biopharmaceutical industry operates as an industry rather than a nonprofit, the bottom line is an important consideration in every aspect of product design. From laboratory automation methods that speed discovery to streamlined manufacturing processes that incorporate the themes of operational excellence, Lean manufacturing, and quality by design, the industry is undeniably focused on minimizing cost and maximizing revenue. At the BioProcess International European Conference and Exhibition, the Scale-Up and Manufacturing track will focus on economic strategy and technology transfer for outsourcing and contract manufacturers, process development and management strategies for operational efficiencies, protein aggregation, scale-up of cell culture and fermentation for production quantities, and strategies for optimizing recovery and purification. Christopher Dale , head of microbial technology at Lonza, USA, will discuss the impact of technology in microbial fermentation on volumetric capacity an...
Figure 1. The same genomic and proteomic technologies used to discover new drugs and therapeutics are also changing the way we live and some of the products we buy. Technologies have yielded new enzyme biocatalysts , used in producing raw and intermediate materials and consumer products. In addition to improving crop and food production, companies are using the tools of biotechnology to manufacture materials from renewable and sustainable resources, build environmentally sound industrial processes, and develop innovative solutions to growing global energy needs. “The renewable fuels and fuel efficiency standards that are now law have created a huge opening for advanced biofuels in the US transportation fuel markets,” said Brent Erickson, executive vice president for the Biotechnology Industry Organization’s (BIO’s) Industrial and Environmental Section, at a recent press conference. “Make no mistake about it,” he stated. “This will be an ongoing project larger than both the Manhattan Project and the Apoll...
When it comes to agriculture, the people of Austria are among the most dead-set against so-called “genetically modified organisms” of any population in Europe ( 1 ). But as is so often the case elsewhere, their attitude toward biotechnology used in medicine is much more friendly. This may have to do with the country’s traditional strength in environmental biotech (ranging from wastewater treatment and organic waste composting to anaerobic digestion for biogas generation) and also food biotechnology. That is the suggestion of Dr. Heribert Insam, who is a professor at the University of Innsbruck’s microbiology institute and editor in chief of the Applied Soil Ecology journal. “Austrian agriculture is based on small family farms,” he explained. “Many have decided to produce according to the regulation of bioorganic agriculture (nearly half of all such farmers in Europe are Austrian). Both from a scientific and marketing perspective, GMO crops do not make any sense here. But Austria has a long tradition in ...
As companies grow and expand their product offerings, it becomes necessary to consider manufacturing space. The decision to build is not made lightly, because CGMP manufacturing space comes at a steep price. Estimates range from $500 to $1,400 per ft 2 to build new biopharmaceutical manufacturing space ( 1 , 2 , 3 ). As Jean-Francois Denault, Agnes Coquet, and Vincent Dodelet point out in their article in the February issue of BioProcess International , non-GMP biomanufacturing space comes at a much lower cost due to the lack of strict regulatory compliance required ( 3 ). A “virtual biotech” company uses this fact to its advantage, contracting out the manufacturing and housing only scientists in an office environment with the leanest approach to this theme. That business model certainly has its advantages in the uncertain world of biopharmaceuticals, where everything rests on costly and lengthy clinical trials. However, companies from small to large with successful products are facing the choice of whe...
Increasing pipelines, shorter timelines, talent scarcity, reduced budgets — all these are issues faced by companies working in today’s biotechnology environment. The ultimate goal of a process development team is to stay off the “critical path” to drug approval. But how do they complete the necessary work to create a robust manufacturing process in light of such pressures? To increase the effectiveness of development, many companies are turning to high-throughput technologies within their development platforms. Such technologies promise that scientists can access larger experimental spaces and thereby improve results of each individual experiment, both reducing the number of optimization iterations and increasing the productivity of each hour spent in a laboratory. PRODUCT FOCUS: ALL BIOLOGICALS PROCESS FOCUS: PRODUCTION PROCESS DEVELOPMENT WHO SHOULD READ: PROCESS ENGINEERS, CELL CULTURE ENGINEERS KEYWORDS: CELL-LINE DEVELOPMENT, CELL CULTURE OPTIMIZATION, MEDIUM OPTIMIZATION, PROCESS DEVELOPMENT LEV...
A rule of thumb in drug development states that the larger a therapeutic molecule is, the more trouble it will be to make, ship/store, and administer to patients. Biotherapeutics include proteins (such as antibodies), vaccines, some smaller peptides (such as hormones), DNA for gene-transfer therapies, cells and tissues, and to a lesser extent blood-fractionation products, allergenics, and RNA/oligonucleotides. Biomolecules are big and unwieldy, they’re produced in complex mixtures by biological processes, and they face numerous challenges in storage and within the environment of a human body. Cells and tissues present an entirely different set of problems, from culture of autologous cells to immune-system problems with allografts. The emergence of regenerative medicine and a move toward a global marketplace are creating a demand for new technologies that allow worldwide shipment of biological products while maintaining their viability or function. Effective biological packaging requires new understanding ...
With the help of rapid advancements in molecular biology and genetic engineering, a rising number of biotherapeutics are being developed and marketed. The quality and safety requirements for this class of active ingredients has steadily increased over the decades since Eli Lilly put forth the first insulin manufactured using genetically modified organisms in 1982. This has led to dynamic developments in protein analysis and proteomics intended to meet a growing demand for new technologies and sophisticated analytical techniques to characterize therapeutic proteins. Meanwhile this new class of drug substances has posed great challenges to regulatory authorities and the pharmaceutical industry, both of which were previously used to dealing primarily with small-molecule drugs. Proteins are much more complex entities, and as a consequence, a complicated set of rules has developed to guide the approval of biotherapeutics. Discussion about regulatory requirements concerning therapeutic proteins has not yet abat...
A new product takes a long and winding road from a laboratory to the patients it is designed to help. Many factors and organizations affect just how many months and dollars it will take to shepherd a new product from preclinical studies to market. Carefully documented, regulatory-compliant clinical trials are key to marketing approval. Clinical trials involve a choreographed network of regulatory agencies, sponsor companies, and clinical investigators. Myriad specialists in that network include those who produce and deliver an investigational product, medical directors, project managers, statisticians, clinical research monitors, institutional and independent review boards (IRBs, also known as ethics committees), recruitment specialists, data managers, contract managers, medical writers, clinical investigators, clinical research coordinators, auditors, regulatory agency inspectors — and the list goes on. Many of those clinical research professionals are employed by sponsor companies. Increasingly, however...
Discovery, development, and commercialization of novel biologics frequently involve collaboration between two or more companies. In the context of these business relationships, transfer of technology from one institution to another is a crucial step that needs to be executed flawlessly and rapidly. Follow-up activities usually include the development of productive, reliable, and scalable processes and are equally important because they are usually on the critical path to market. PRODUCT FOCUS: MONOCLONAL ANTIBODIES PROCESS FOCUS: TECHNOLOGY TRANSFER (PRODUCTION) AND ANALYTICAL METHODS DEVELOPMENT WHO SHOULD READ: PRODUCTION AND PROCESS DEVELOPMENT, MANUFACTURING KEYWORDS: IGF-1R, EXPRESSION, TECH TRANSFER, CELL-LINE CULTIVATION, SIZE-EXCLUSION CHROMATOGRAPHY, ISOELECTRIC FOCUSING, MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME-OF-FLIGHT MASS SPECTROMETRY, ELECTROSPRAY IONIZATION MASS SPECTROMETRY LEVEL: INTERMEDIATE In the context of the licensing of a therapeutic antibody for the treatment of canc...
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Successfully driving your global business requires vigorous, secure information exchange within your facility, from site-to-site, and with your partners and contract service providers. Tools to capture data in real time support decision making and enable companies to manage volumes of historical data needed for regulatory submissions. Software is available for data mining, managing clinical trial networks, and assessing toxicology data (among many other things). Information technologies in the biotechnology industry facilitate development and delivery of new therapies and diagnostics, improvements in patient care, and other life-science and healthcare technologies, goods, and services (see “A Sampling of IT” products box). Those who were working in the biotech industry in 1997 when 21 CFR Part 11 was introduced — detailing the FDA’s then-new requirements for incorporating electronic records and signatures — will remember how daunting those processes appeared to be (and how expensive) ( 1 , 2 , 3 ). Enforc...
Biopharmaceuticals such as recombinant monoclonal antibodies (MAbs) account for a significant proportion of all new drugs ( 1 , 2 , 3 ). Although manufacturing site capacities have expanded and process efficiencies have improved greatly, there is still some concern the current biomanufacturing capacity worldwide might not meet increasing market demands ( 1 , 2 ). PRODUCT FOCUS: RECOMBINANT PROTEINS PROCESS FOCUS: PRODUCTION PROCESS DEVELOPMENT WHO SHOULD READ: QA/QC, PROCESS DEVELOPMENT, AND ANALYTICAL PERSONNEL KEYWORDS: CELL LINE DEVELOPMENT, SCREENING ASSAY, MONOCLONAL ANTIBODIES, FC PROTEINS, CHO, IGG, HTRF, ANTIBODY TITER, CELL LINE PRODUCTIVITY, ELISA LEVEL: INTERMEDIATE One aspect of bioprocessing that significantly affects production capacity requirements is cell line productivity ( 3 ). A high-producing cell line requires less capacity and reduces overall cost of goods than a lower-producing one ( 3 , 4 ). Thus, efforts to reduce capacity requirements usually begin with cell line selection...
Since the turn of the century, industry analysts have touted the “coming of age” of the biotech industry — and they’re inevitably talking about biopharmaceuticals. In fact, biotech has become the innovation engine for the pharmaceutical industry as a whole. Advances in genomics, proteomics, and other biotech research are bringing about not only new drug molecules, but also whole new therapeutic classes such as gene and cell therapies. Biotherapeutics represent the fastest-growing segment of the pharmaceutical industry, with more than 200 marketed products and hundreds more in development. The maturation of this industry has created in its leaders an urgent desire to find solutions to manufacturing problems. Some perennially successful biotech companies such as Amgen and Genentech are joining the ranks of “Big Pharma” themselves, and “Little Biotech” isn’t so little anymore. And a grown-up industry has grown-up concerns. Any discussion these days of biomanufacturing systems inevitably falls under the growi...
Many models are available for establishing a quality system in regulated industry, whether for pharmaceuticals, medical devices, or biologics. Each company establishes a set of standard operating procedures (SOPs) that enables it to manage operations and then implements a quality system around its product and process. But why do some quality systems work well, whereas others falter or fail miserably? Does the fault lie in procedures, implementation, or maybe training? Perhaps the answer can be found by examining the involvement of senior management. Global Expectations for Quality Systems Management The FDA’s GMPs for pharmaceutical manufacturers under 21 CFR 211.180(f) requires that “responsible officials of the firm are notified either in person or in writing via an investigation when deviations occur” ( 1 ). Section 211.180(f) requires that “responsible officials of the firm … are notified in writing of any investigations concerning failures, complaints, returned product, or salvaging operation” ( 1 )....
We invite you to the 2008 BIO International Convention, Tuesday–Friday, 17–20 June 2008. Biotechnology innovations are addressing the world’s challenges to heal, fuel, and feed growing and changing populations. Our event cochairs (Catherine Mackey, PhD, senior vice president of Pfizer in La Jolla, CA, and Greg Lucier, chairman and CEO of Invitrogen Corporation in Carlsbad, CA) have focused the 2008 event theme and program to highlight this important role of biotechnology: Innovate. Heal the World. Fuel the World. Feed the World. Thank you to the BioProcess International editors, who created this supplement to provide us insight into the trends, insights, and relationships between topics in the 2008 BIO International Convention breakout sessions and product focus zones within the BIO Exhibition. We hope you will use “myBIO” online tool to sort through the event content and customize your schedule to meet your business needs. Hundreds of new companies are taking part in the BIO Exhibition. You can easily ...