Genetic Engineering & Biotechnology News

MAY15 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Genetic Engineering & Biotechnology News | GENengnews.com | MAY 15, 2018 | 19 tification and characterization might reveal an impurity that hadn't been present before, or that hadn't been identified even though it had been present before. GEN: What are the major challenges in implementing a continuous process in downstream operations? Dr. Bulpin: Process intensification, the forerunner of continuous manufacturing, is already hav- ing significant impact of cost of goods sold (COGS) where it is being implemented. For instance, one customer reported a 75% re- duction in COGS. COGS will continue to fall as we operate our process in connect and continuous modes. The key business risk, however, will be clearing regulatory hurdles as processes look less like a series of sequen- tial operations and more like an automated assembly line. Delays in product approvals have a major impact on revenue and market position driving a risk-averse culture. We, as suppliers, biomanufacturers, and regulators, must work together to build the regulatory framework for approval of next- generation processes. MilliporeSigma contin- ues to collaborate with drug manufacturers, as well as other single-use suppliers, to stan- dardize test methods for single-use systems and to ease the implementation and regula- tory filing challenges associated with continu- ous manufacturing. Dr. Levison: We see that the major hurdle here is unfa- miliarity and lack of trust, so for the last few years, the message at Pall Biotech has been clear: Contrary to widespread belief, there are minimal challenges in the adoption of fully continuous or semicontinuous processes. There is nothing that is more difficult or costly to implement than traditional tech- nologies. The [new] processes even use the same buffers, filtration media, and chroma- tography adsorbents—just more efficiently. And the same technologies are used, just in a different configuration. Ms. Gebski: More efficient seed-train expansion and up- stream continuous processing are challenges that are being met with high-performance cell retention systems such as KrosFlo ® TFF and XCell™ ATF. Perfusion cell culture de- livers a harvest feedstream ready for purifi- cation, thus effectively linking upstream and downstream operations, the first step in con- tinuous processing. Challenges in implementing downstream continuous processes center on the connec- tion and automation control of multiple unit operations. Individual unit operations, from multiple chromatography steps to viral filtra- tion, must be transitioned from batch to con- tinuous, and then multiple, optimized contin- uous unit operations must be linked to derive a fully continuous downstream process. A significant amount of process develop- ment and automation layered on top is re- quired as compared to standard batch pro- cessing, but advanced bioprocessing compa- nies will make hybrid-continuous and fully continuous processing a reality in the next five years, as advances in system integration and control functionality enable the linking of technologies. Dr. O'Donnell: A major challenge in continuous downstream processing is marrying complex equipment with the design of single-use technologies. What happens when a valve, detector cell, or pump head in a very complex method fails? Does the whole process result in a failed man- ufacturer lot? The aversion to increased risk will supersede efficiency, particularly when the process purifies a particularly high-value product. In addition, the training of manu- facturing personnel to properly operate and monitor complex processes will always be a major concern. GEN: What has been your company's approach to solving the downstream bottleneck issue? Dr. Bulpin: An evolutionary approach must be taken to- ward integrated and continuous processes. Process intensification, like multicolumn chromatography or the implementation of single-pass TFF, has been a successful first step. We are now in the process of connecting operations such as anion exchange and virus filtration into a single operation. Based on this learning, MilliporeSigma will develop software and automation capa- bilities that don't yet exist to fully connect and integrate both upstream and down- stream processes to enable continuous pro- cessing. Software must enable processing sys- tems to communicate and integrate several operations to maintain process controls and product quality. Sensors and process analyti- cal technology strategy are needed to drive control and automation decisions. Biomanufacturers are clamoring for this type of software and control platform, and we are moving swiftly to deliver it. Next- generation processing is a key strategic focus area for us, and we are committed to leading the industry in this processing evolution. For decades, MilliporeSigma has collaborated with our customers to shape drug production processes, and it will continue to do so. Dr. Levison: Our products and services can be tailored to support traditional, single-use, continuous, semicontinuous, and hybrid drug manufactur- ing needs. From a services perspective, we sup- port production from early-phase development to commercial manufacturing. And from a technology perspective, working independent- ly or as a member of the Danaher Life Sciences network, we develop tools that deliver all the right resources for lifetime solutions. We want to deliver efficient, flexible op- tions, and we have no desire to push custom- ers in any one specific direction. Whether we are providing one consumable or piece of equipment, or a full lineup of Pall Biotech products, we simply want to meet every cus- tomer's needs. Ms. Gebski: Downstream bottlenecks can be resolved by improving or reducing process steps. Repligen technologies are available in single-use and ready-to-use formats that enable more efficient downstream process- ing. SIUS ® TFF cassettes are purpose-built, single-use cassettes that eliminate the need for post-use cleaning, testing, and storage, ultimately reducing buffer usage and the la- bor required for support. ProConnex ® hol- low-fiber flow paths are supplied gamma- irradiated and fully assembled, enabling expedited setup and reduced manufactur- ing downtime. OPUS ® prepacked columns are the most configurable and platformable prepacked columns in the bioprocess industry, with di- ameters ranging from 0.5 to 80 cm. OPUS columns enable time savings, cost savings, and reproducibility in downstream process- ing, thus reducing process development cycles, time to clinic, and overall cost to manufacture. With configurability for shorter bed heights and matched pressure-flow performance across multiple columns, OPUS columns are well suited for multicolumn chromatography applications, thus also enabling continuous downstream processing. Dr. O'Donnell: Tosoh Bioscience, with its full line of process resins, can manufacture chromatographic resins with varying pore and particle sizes. By optimizing chromatographic resins with enhanced kinetic performance, multicolumn continuous chromatography can be ac- complished with smaller columns and with potentially decreased complexity. This will decrease the cost of production, reduce risk in some cases, and facilitate better training of manufacturing personnel. THINK BEYOND CHO, THINK ESETEC ® COST SAVING WITH ESETEC ® – 3X LOWER COGS ESETEC ® CHO $/g CREATING TOMORROW'S SOLUTIONS What if there were an innovative secretion system for production of your non-glycosylated biopharmaceutical that made your processes faster and more cost-effi cient? That would be great – and it is possible. ESETEC ® is your way out of the hamster wheel. WACKER's patented E. coli secretion technology combines rapid growth of microbial systems with real protein secretion. It outperforms mammalian CHO cells thanks to superior productivity, shorter development times and lower cost of goods sold. Unbelievable yet true: by applying cutting-edge process-simulation tools, we demonstrated that cost of goods sold for ESETEC ® manufacturing is as much as 3 times lower than CHO. And when are you going to opt for more effi ciency? Contact us via www.wacker.com/biologics. Wacker Biotech GmbH, Jena and Halle, Germany, Tel. +49 3641 5348 - 206, info.biologics@wacker.com Bioprocessing

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