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From time to time we each experience the hurry to get somewhere, only to end up waiting for someone or something else. Today’s air travel seems to be nothing but “hurry-up-and-wait”: After you race to the airport two hours before your flight time, the plane ends up departing two hours late. Businesses suffer from the same disorder. For example, in the biopharmaceutical industry, this phenomenon is often evident in all the documentation that must be completed before a product can be released for shipment. Most of us seldom give it much thought, but delaying the shipment of a drug (especially a blockbuster) can cause business executives to become quite agitated. “Delayed shipments of our blockbuster drug could mean another ‘beating’ from Wall Street analysts and our shareholders,” an executive might bemoan, “more warehousing costs associated with quarantined product, and making more concessions to retain our customers. It just seems like we are always hurrying up and then waiting.” Amazingly, when we stop, ...
Host cell proteins (HCPs) are process-related impurities derived from a host cell expression system that may be present in trace amounts in a final drug substance. During biologics development, it is important to demonstrate that a bioprocess is efficient in removing HCPs and that it provides consistent control of HCP levels. Several techniques are typically used for detection, quantitation, and risk evaluation of HCPs in biologics. The most common are enzyme-linked immunosorbent assays (ELISAs), Western blotting, sodium-dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and chromatographic separation methods ( 1 ). Genomics, proteomics, and bioinformatics also have been used recently in analysis and evaluation of host cell proteins ( 2 ). PRODUCT FOCUS: MONOCLONAL ANTIBODIES PROCESS FOCUS: PRODUCTION AND DOWNSTREAM PROCESSING WHO SHOULD READ: MANUFACTURING, PROCESS DEVELOPMENT, QA/QC KEYWORDS: ELISA, HOST-CELL PROTEINS, WESTERN BLOTTING, CROSS-REACTIVITY, RISK MANAGEMENT LEVEL: INTERMEDIATE
Scale-up studies are needed for assessing cell culture production system options and for testing nutrient supplementation techniques as well. With the many supplementation options available, choices need to be made as early in product development as possible because advantages can change with scale. One published fed-batch scale-up study testing from 3 L up to 2,500 L highlights items to be considered in addition to the nutrient supplementation process such as the impact of pH and CO 2 control ( 1 ). That thorough study showcases epratuzumab biomanufacturing, which passed two global phase 2 clinical trials and met all specifications for process robustness, product consistency, and reproducibility. As cultures increase in cell concentration and volume during scale-up into bioreactors, not only are nutrients depleted, but waste products can accumulate to sufficient levels to limit product formation. As a metabolic end product of glucose metabolism, lactate is usually considered to be detrimental to culture...
In recent years biopharmaceutical manufacturing has demonstrated major improvements in MAb production, exhibiting product titers as high as 25 g/L often associated with very high cell densities ( 1 ). High-density cell cultures with >150 million cells/mL pose a great challenge in clarification and further downstream processing because of a need to remove a large amount of biomass and increased levels of contaminants from cell debris generated during cell culture and harvesting. Production of biological substances (MAbs, in particular) usually involves processing a complex cell culture broth from which desired biological substances must be isolated and purified while maintaining high overall product recovery and quality. The eXtreme-Density (XD) cell culture process is a continuous process in which both cells and product are retained in a stirred-tank bioreactor using suspension culture of Crucell’s ( www.crucell.com ) PER.C6 human cells ( 1 , 2 ). This is accomplished by the use of a modified alternating ...
Technological advancement has taken protein expression titers from concentrations measured in mg/L to those measured in g/L over just a few years ( 1 ). Annual demand for antibodies has reached several metric tons, which has spurred production of >100 kg batches of protein at a time ( 2 ). As upstream yields continue to increase, downstream purification involving process solution preparation and delivery must increase in proportion to keep pace with demand. That has placed facility and instrumentation capacity constraints front and center in the biomanufacturing industry, where many are directing resources toward eliminating the resulting bottlenecks through increased productivity and efficiency of downstream unit operations ( 1 , 2 ). As shown in Photo 1, in-line buffer dilution (IBD) technology has emerged as a process analytical technology (PAT) solution to this dilemma ( 3 ). This technology is based on in-line mixing of buffer concentrates (typically 10×) with a diluent (often water) to yield a 1× pr...
Inline Sampling Product: STA-PURE fluid sampling Applications: PAT sampling Features: Gore’s sampling system can be directly connected to 25-mm Ingold ports. Previously, such sampling required the use of TC adapters and O rings that can leak or get stuck in vessel ports. The STA-PURE solution uses a high-purity, highly compressible platinum-cured silicone adapter integrated with a single valve device. A single-use silicone sleeve is attached and presterilized with the device. When the valve body is inserted into a vessel port, the sleeve rings are compressed significantly to create redundant seals that will withstand >100-psi fluid pressure. Contact W.L. Gore & Associates, Inc. www.gore.com/pharmbio Membrane Chromatography Product: Mustang Q XT chromatography capsules Applications: Biopharmaceutical contaminant removal Features: Mustang Q XT chromatography capsules help process developers reduce purification time, increase throughput, and cut costly buffer consumption. The open-pore structure of M...
IBC’s Biopharmaceutical Development and Production Week covers today’s critical issues from all angles to provide you with a deeper understanding of the forces affecting your company and driving the bioprocessing industry. Customize your learning and networking experience with access to Together, these five conferences deliver the latest technical and scientific approaches in upstream and downstream processing to accelerate development and optimize production. Benchmark your latest QbD/DoE efforts against those of industry leaders. Learn how new process validation guidelines will affect your manufacturing decisions. Hear how companies are integrating upstream and downstream processing and building a stronger connection with analytics at the process interface. Obtain practical tools and approaches to help make the best outsourcing decisions for your company’s needs. Examine proven approaches to ensure successful process and method transfers. Use proven approaches to overcome the upstream and downstream cha...
This past fall, we collaborated with researchers from MIT and Harvard Business School to develop and launch the Pharmer’s Market, a prediction market that aggregates the opinions, insight, and experience of a wide range of pharmaceutical professionals to forecast outcomes of drug clinical trials. The market is designed to be a showcase of how pharmaceutical development could run in the future. This concept was born when we agreed on a critical premise: Discovery should be a collective process. That isn’t exactly how pharmaceutical companies work at present. So the question is how to implement collaborative technologies that can help companies become more efficient and better equipped in the current industry climate. The vast majority of these technologies are qualitative and thus unable to measure anything that really matters. This is where prediction markets have the power to create a fundamental shift in pharmaceutical industry thinking. How It Works Essentially, prediction markets gather insight from a...