Bioprocess scale-up: quest for the parameters to be used as criterion to move from microreactors to lab-scale

Advances in high-throughput process development and optimization involve the rational use of miniaturized stirred bioreactors, instrumented shaken flasks and microtiter plates. As expected, each one provides different levels of control and monitoring, requiring a compromise between data quantity and quality. Despite recent advances, traditional shaken flasks with nominal volumes below 250 mL and microtiter plates are still widely used to assemble wide arrays of biotransformation/bioconversion data, because of their simplicity and low cost. These tools are key assets for faster process development and optimization, provided data are representative. Nonetheless, the design, development and implementation of bioprocesses can present variations depending on intrinsic characteristics of the overall process. For each particular process, an adequate and comprehensive approach has to be established, which includes pinpointing key issues required to ensure proper scale-up. Recently, focus has been given to engineering characterization of systems in terms of mass transfer and hydrodynamics (through gaining insight into parameters such as k(L)a and P/V at shaken and microreactor scale), due to the widespread use of small-scale reactors in the early developmental stages of bioconversion/biotransfomation processes. Within this review, engineering parameters used as criteria for scaling-up fermentation/bioconversion processes are discussed. Particular focus is on the feasibility of the application of such parameters to small-scale devices and concomitant use for scale-up. Illustrative case studies are presented. (c) 2010 Society of Chemical Industry