Over the last few years, the challenges of vaccine development have created perhaps an unprecedented level of scrutiny, not just within the biotech industry, but also in the consciousness of the general public. This was certainly the case during the recent H1N1 influenza outbreak. The demand to know when a vaccine would be available, and if producers could meet the global demands consistently made front page news. The challenge of rapid and scalable manufacture is of course nothing new in biopharmaceutical development and in many respects, monoclonal antibodies are leading the way as the industry moves towards the required level of industrialization.
Category: <span>Cell Lines</span>
An interesting situation occurred ten years ago in an industry where quality had been the critical factor in management decision-making. Quality was abruptly bumped to second place behind pricing, which started a global rush to find lower-cost suppliers and eventually resulted in massive outsourcing. During this evolution, the importance of quality systems for the pharmaceutical and biopharmaceutical community was recognized by regulatory agencies that began establishing risk management standards.
With increasing time pressures to move biological therapeutics into the clinic, bioprocessing development studies have to be limited. Currently, core studies typically involve the use of shake flasks and benchtop bioreactors to select the most productive clones, optimum media, and bioprocessing conditions. The capacity for using benchtop bioreactors is especially limited as it is resource-intensive and has high capital equipment and infrastructure costs. Consequently, scientists frequently cannot perform full design-of-experiments (DoE) and are generally only able to take one or two of their most promising clones forward for partial DoE runs in benchtop bioreactors.
The rapidly growing interest for cell and gene therapies demands the development of robust, scalable, and cost-effective bioprocesses for viral vector production. For the production of lentiviral vector (LVV) at high titers, we have developed an inducible packaging system in suspension HEK293 cells from which we can also generate stable producer cell lines, in serum-free conditions. To evaluate the potential of this platform, we have generated a stable cell line that produces an LVV encoding a green fluorescent protein (GFP) and obtains 10E+07 to 10E+08 transduction units (TU)/mL at the 4 L, 10 L and 50 L scales. Functional LVV titers were maintained across all scales in bioreactors with different configurations and geometries indicating process robustness. Further, the addition of 10% feed increased the volumetric productivity by 3.5-fold in comparison to batch production, making our platform suitable for large-scale LVV production and showing a real potential for commercial manufacturing.