Genetic Engineering & Biotechnology News

SEP15 2017

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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Page 47 of 77

10 | SEPTEMBER 15, 2017 | by LEWA, also uses the CaptureSMB twin-column approach (under license from ChromaCon) for manufacturing- scale GMP processes. Like Contichrom CUBE, EcoPrime Twin performs tradi- tional batch chromatography, with one column or two columns in series, and incorporates an in-line dilution option for preparation of point-of-use buffers from concentrates. Together, Contichrom CUBE and EcoPrime Twin represent a complete scale-up platform for continuous chro- matography, from bench to produc- tion. "Because steady state is achieved almost immediately, the bench-scale and production systems perform nearly identically, which allows great confidence in scale up," says Gerard Gach, chief marketing officer at LEWA-Nikkiso America. Recent LEWA studies 1 compar- ing batch and continuous capture of equivalent process volumes, showed process times of four hours for con- tinuous processing vs. nine hours for batch capture. Specific productivity, measured as grams of product per li- ter of resin per hour, is up to threefold higher for continuous capture with both Contichrom and EcoPrime Twin compared with batch chromatogra- phy, and total buffer consumption was 20–50% lower relative to batch capture. "Little process development work was done to accomplish a nearly opti- mized run," Gach adds. EcoPrime Twin may be optimized for either shorter process time or improved resin utilization. LEWA esti- mates that for a 100-kg batch at 1g/L titer, approximately $900,000 in resin costs, or 22 days of process time for a comparably sized upstream culture, can be saved. A side-by-side com- parison on a 5 g/L-titer mAb process stream showed nearly identical benefits for EcoPrime Twin and Contichrom CUBE. Thus, the lab-scale experiments can be used to accurately predict the scaled-up process performance. Yes, It Works During batch mAb capture with Protein A resins, antibody loads onto columns at well below total resin ca- pacity to prevent sample breakthrough and subsequent product loss. Scientists at GE Healthcare have demonstrated that continuous capture through periodic countercurrent chromatogra- phy (PCC) increases resin utilization through loading levels that are signifi- cantly higher than in batch processing. But as columns are loaded beyond breakthrough, resin lifetimes may be shortened as a result of fouling, for ex- ample, thus attenuating a major benefit of downstream continuous processing. Considering the large sample loads when running in PCC mode, precipita- tion of HCPs and fouling could further degrade performance. "Protein-ligand degradation can also arise from repeti- tive alkaline treatment during cleaning- in-place, or degradation from proteases from the feed material during sample loading," says Mats Gruvegard, bio- process downstream senior marketing manager at GE Healthcare. A recent GE study demonstrated 2 that more than 175 cycles of PCC per- forms similarly to a conventional high- capacity resin during continuous cap- ture. Specifically, MabSelect SuRe PCC affinity resin offers high binding capac- ity at shorter residence times, making it well suited for applications requiring fast mass transfer such as mAb capture in a continuous process. The resin is based on a high-flow agarose base ma- trix with average bead size of 50 μm. Bottom line: PCC capture sig- nificantly improves resin capacity utilization and maintains performance compared with batch processing. MabSelect SuRe and MabSelect SuRe LX showed comparable performance with respect to clearance of host-cell proteins, leached Protein A, and mAb concentration in the eluent), but under test conditions, the LX resin had about 20% lower binding capacity. "Previously, GE Healthcare scien- tists confirmed a 56% increased resin capacity utilization in PCC versus batch, using MabSelect SuRe LX as the capture resin," Gruvegard says. "Pro- ductivity gains may be exploited to re- duce the amount of resin required for a given process or to increase the overall process output." Process-Specific Adoption Procrastinators will rejoice at the anticipated timeline for adoption of fully continuous bioprocesses. Dr. Phillips predicts commercial viability will take at least 5–10 years due to the complex interplay of economics, engi- neering, and product availability. "Economic studies will be highly process- and organization-specific," says Cameron. Continuous biopro- cessing can help organizations move manufacturing capital spend into operational spend, deferring risk and increasing working capital. It may play out similarly to how single-use allowed companies to be able to defer capital spend until late in clinical trials when success was more assured, and to quickly reconfigure factories." For some, continuous downstream processing makes economic sense, while for others a combination of continuous and discrete unit operations might work better. Some indicate that continuous cell culture plus batch purification is the way to go. "In the end, manufacturers must do their own calculations and de- cide based on their specific situation." According to Cameron, companies aren't approaching continuous on a product basis, but instead, are looking at parallel development of a continuous platform that can be deployed across molecules within a specific process type, for example, Chinese hamster ovary (CHO) and mAbs. "This al- lows [companies] to address on-time to-market concerns while also taking advantage of the potential benefits of a continuous process." References available online. Continuous Bioprocessing Is Coming Continued from page 8 CO N T I N U O U S B I O P R O C E S S I N G

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