Genetic Engineering & Biotechnology News

OCT15 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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24 | OCTOBER 15, 2017 | | Genetic Engineering & Biotechnology News Andrew Magno, Gary Tompkins, Travis Scagliarini, and Miles Scotcher, Ph.D. The cell-line development process starts with in silico procedures combining co- don-optimization algorithms, a secretion signal toolbox, flexible expression vec- tor configurations, and high-productivity CHO-K1 cell lines. Machine learning combined with in vitro screening is used to consider the end prod- uct and final process from the onset of the project. Process development can be done in parallel with clone development, thus reduc- ing the number of steps and shortening the overall project time. Screening is performed using 96-well plates in an automated platform and either transient HEK cells or stable CHO cells. Multitron Pro incubation shakers config- ured for 96-well plates are used (3 mm or- bit/1,000 rpm mixing). The shakers control all critical running parameters (agitation, temperature, CO 2 ) and have active humidi- fication to minimize evaporative losses. This ensures a consistent and reproducible growth environment from 1-mL volumes in 96-well plates to 5-L flasks. Each shaker has a capacity of up to 80 plates (7,680 wells). This makes it possible to test large numbers of clones and run- ning conditions in triplicates, and to gen- erate statistically significant data in every screening pass. Following the initial screening in 96-well plates, the most promising clones are trans- ferred to 24-well deep-well plates and fur- ther evaluated prior to scaling up (Figure 1). Down-Selection After initial screening and down-selec- tion of stable CHO cell lines, the top candi- dates are ranked and selected for productiv- ity. The eight best clones are then cultured in 125-mL flasks for 14 days in a Multitron Pro (Infors) with 25-mm orbit and 150-rpm agitation (Figure 2). Following down-selection, the cell cul- ture can be scaled up further using incuba- tion shakers. One Multitron Pro incubation shaker can hold seven Thomson 5-L flasks, each with a working volume of 2.4 L. This translates to 17 L per shaker and 50–85 g of a typical IgG1. A triple stack of Multi- tron Pro shakers has the capacity for 50 L of cell culture. In other words, it is possible to produce 150–255 g of antibody in a normal 10–14 day campaign using three incubation Screening to Small-Scale GMP Biomanufacture Bioprocessing Figure 2. Productivity of the eight most- productive clones derived from stable transfection of a transposon-based IgG1 expression construct in HD-BIOP3 GS null CHO-K1 cells (Horizon Discovery). Cells were grown in non-optimized 14-day fed-batch 125-mL shake flask culture. The specific productivity of clonal isolates was >40 pg/cell/day. Figure 1. Productivity of the top 22 clones derived from stable transfection of a transposon- based IgG1 expression construct in HD-BIOP3 GS null CHO-K1 cells (Horizon Discovery). Cells were grown seven days in a 24-well deep well-plate under non-optimized conditions. Insights Bioprocessing Catalent said it agreed to acquire Cook Pharmica for $950 million in a deal that would continue the consol- idation of contract development and manufacturing organizations (CDMOs)—to which biopharmas have increasingly outsourced operations—and bolster the buyer's biologics capabilities. The acquisition would join Cook Pharmica's drug substance and drug product manufacturing and relat- ed services with Catalent's development, delivery, and supply operations—creating a combined company that, the buyer says, would strengthen its position in biologics development and analytical services, manu- facturing, and finished product supply. The deal further advances global consolidation of the CDMO market, which has seen the closing of two multibillion-dollar transactions this year. One was Thermo Fisher Scientific's approximately $7.2-billion acquisition of Parexel, which was announced May 15, 2017 and completed August 29, 2017. The other was Lonza's $5.5-billion cash purchase of Capsugel, a drug capsule and delivery systems firm, from its pri- vate equity owner KKR, announced in December 2016 and completed July 6, 2017. Also among 2017 CDMO deals, affiliates of The Car- lyle Group and GTCR on August 31 completed their acquisition of Albany Molecular Research (AMRI) for about $922 million cash, while JSR Life Sciences agreed in June 2017 to acquire mammalian cell-line development specialist Selexis and integrate it with KBI Biopharma, a company which Japan-based JSR acquired in 2015. Catalent says the Bloomington facility's biomanu- facturing capacity and expertise in sterile formula- tion and fill/finish across liquid and lyophilized vials, prefilled syringes, and cartridges "perfectly aug- ments" its current expertise in cell-line engineering, bioconjugate development, analytical services, bio- manufacturing, prefilled syringe technologies, and blow/fill/seal technologies. "The complementary biologics development, bio- manufacturing, and fill/finish capabilities of Catalent and Cook Pharmica will provide biopharmaceutical firms with a single, integrated partner supporting a wide range of clinical and commercial needs," Catal- ent chair and CEO John Chiminski said in a statement. "We are very excited to join forces with the tal- ented Cook Pharmica team in Bloomington, IN, and plan to invest aggressively there, in our rapidly expanding Madison, WI, facility, and in the rest of the Catalent Biologics network to build a true global leader in the biologics market, which will help us to improve the lives of patients around the world," Chiminski added. n Catalent to Acquire Cook Pharmica for $950M Tutorial Exploring a Simple, Unified Platform Strategy for Handling a Range of Cell Culture Needs

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