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Apr 1, 2010 (Vol. 30, No. 7)

Cell Culture Moving Past Previous Technical Limits

Researchers Employ Insect and Duck Cells, Novel Media, and Next-Generation Automation Technologies

  • Cell Lines

    In 2006 MedImmune was awarded a Department of Health and Human Services (HHS) contract to develop a cell culture system for seasonal and pandemic flu. The project involves both upstream and downstream work and, according to George W. Kemble, Ph.D., vp of R&D and GM, “we came up with a robust program.”

    The vaccine is based on the Madin-Darby Canine Kidney (MDCK) cell line. When compared to several other popular, potential substrates for virus production, “MDCK cells supported high levels of vaccine virus production for multiple different live attenuated influenza vaccine (LAIV) subtypes in both serum-containing and serum-free media. These results suggest that MDCK cell-based production can be used as an alternative production platform to the currently used egg-based LAIV production system,” Dr. Kemble explains.

    “Lab-scale bioreactors can produce 10,000 to 100,000 doses or more with this cell line,” he adds. Additionally, this cell line has a lower tumorigenic potential than many other similar cell lines used for vaccine development.

    MedImmune has developed “a more robust, purification process,” Dr. Kemble says, because live viruses can’t tolerate the harsh conditions typical for inactivated viruses. This new process is at “late preclinical stage now. An IND has been submitted to CBER,” and MedImmune is talking with HHS about how to proceed. As it moves into clinical trials, “we’ll probably use a prototype pandemic virus strain.”

  • Automation

    Click Image To Enlarge +
    According to The Automation Partnership, ambr™ mimics the characteristics of classical bioreactors at microscale.

    As cell-culture applications grow, so does the need for automation. In response, The Automation Partnership (TAP) introduced ambr™, an automated microbioreactor system, earlier this year. This system replicates the conditions in 5–10 L bioreactors within 10–15 mL vials. The system also provides stirred sparged culture with closed loop control of DO and pH along with automated sampling and feeding.

    “Results from ambr’s beta testers have shown that the productivity values match those of larger bioreactors for fed-batch processes,” according to Richard Wales, Ph.D., systems development. Those early users also found a correlation in the amount of protein produced.

    In many labs, “there’s a queue for bioreactors,” Dr. Wales says. “People tell us one FTE can manage four to eight bench-scale bioreactors at the 2 to 10 liter scale.” In contrast, that same FTE can manage 24 microbioreactors in the ambr system in only a quarter of the time. “There’s quite an overhead associated with larger bioreactors,” he explains, in terms of labor and cleaning, as well as materials consumption.

    In contrast, ambr automates tedious tasks, including set-up, feeding, sampling, and maintenance. This saves a significant amount of time, as does the disposable nature of the bioreactors. ambr reportedly has applications throughout the biodevelopment process, but TAP is focusing initially on cell-line selection and characterization and early process development.

    Another recent addition to cell-culture automation, TAP’s Sonata™ cultures and processes insect and mammalian cell lines in shake flasks. It can count cells, add and decant media, centrifuge and harvest cells, and provide refrigeration, allowing optimization to occur at any time, thereby increasing workflow, Dr. Wales says. With automation, “you get a much higher level of consistency.”

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