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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20 | SEPTEMBER 15, 2017 | | Genetic Engineering & Biotechnology News ers often use subculturing studies that assess cell productivity over multiple (60 to 160) generations. However, these studies are both time- and resource-intensive, and, according to Terry McWade, CEO at Valitacell, they're not always effective: "High numbers of cells are being brought to the last stage [of devel- opment], and then companies are finding that many of those cells are actually not stable." In 2014, Valitacell founders McWade and Jerry Clifford asked themselves if they could recreate the bioreactor environment by coating a 96-well plate with small-mole- cule chemicals that mimic different stressors, prompting the development of Valitacell's latest product: ChemStress Fingerprinting. Combined with a software platform that plots growth and product titer for each chemical challenge, ChemStress produces a fingerprint unique to the cell clone and cul- ture media combination tested. Scientists can use changes in the fingerprint to detect clonal instability (Valita™STABILITY), as well as batch-to-batch variation in culture media (Valita™QC). "The key exciting part of the [ChemStress] technology," said McWade, "is the ability to determine much, much more quickly which cells are likely to be unstable." While con- ventional subculturing studies can take 60 to 160 days, ChemStress Fingerprinting can detect clonal instability in 24 days. Decreasing the time and money spent on cell line development can relieve some of the economic pressure biopharmaceutical com- panies face as newer, more targeted thera- pies emerge, requiring more projects, faster development, and more efficient processes. Not only has this pressure prompted innova- tive new solutions, but it has also provided incentive for manufacturers to re-evaluate established technologies. Some companies are even designing media specifically for con- tinuous biomanufacturing operations. Perfusion Hollow-Fiber Bioreactors: An Old Trick for New Processes Patented in 1974 by Kruznak et al., perfusion hollow-fiber bioreactors (PHFB) consist of bundles of thousands of hol- low fibers constructed from semipermeable membranes and enclosed in a cylindrical cartridge. Similar to capillaries within the body, the porous membrane structure of the fibers allows oxygen and nutrient transport to cells immobilized on the exterior of the fibers and removal of waste products. The fiber bundles also increase the surface area available for cell growth considerably, which promotes a higher, more tissue-like density (~10 8–9 cells/mL) than fed-batch bioreactors (~10 7 cells/mL). One of the greatest advantages of PHFBs, however, is the ability to maintain cells in cul- ture for several months at a time. Scott Wa- niger, vice president of bioprocessing at C3, remarked, "biotechnology has kind of been lagging behind the rest of the industrial world when it comes to continuous manufacturing." PHFBs could make a significant contribution to closing this gap, especially compared to the 14 – 21-day runs typical of fed-batch reactors. Continuous manufacturing strategies can sig- nificantly reduce costs, enabling the produc- tion of "difficult-to-express" proteins that fall below the standard production rate of 1 to 10 g/L, making them too costly to produce using conventional methods. C3, a contract development and manu- facturing organization (CDMO), has used perfusion technology since 1981. Their larg- est bioreactor, the Acusyst (automated cell culture system) Xcellerator, runs 20 single- use hollow-fiber cartridges in parallel to ac- commodate a 1,600-L volume. The refriger- ator-sized bioreactor is modular and can be scaled out by adding more units to increase the volume for large-scale production. In ad- dition to providing a linearly scalable system, the design also eliminates the need for seed trains, which can increase time to production and requires additional bioreactors to gradu- WE BRING LIFE TO YOUR LABORATORY. Explore & get your free demo at Shakers | Bioreactors | Bioprocess Platform Software Connect and manage different systems. One single solution to unify all your equipment and data. eve ® – the revolutionary bioprocess platform software. © Space Telescope Science Institute Cell Culture Optimization Continued from page 18 Bioprocessing Manufacturing engineers formerly used complex media from animal- derived products, but the burgeoning, modern-day industry is quickly adopting chemically defined media wherever possible JVisentin/Getty Images

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