The development and application of high throughput cultivation technology in bioprocess development

This review focuses on recent progress in the technology of high throughput (HTP) cultivation and its increasing application in quality by design (QbD) -driven bioprocess development. Several practical HTP strategies aimed at shortening process development (PD) timelines from DNA to large scale processes involving commercially available HTP technology platforms, including microtiter plate (MTP) culture, micro-scale bioreactors, and in parallel fermentation systems, etc., are critically reviewed in detail. This discussion focuses upon the relative strengths and weaknesses or limitations of each of these platforms in this context. Emerging prototypes of micro-bioreactors reported recently, such as milliliter (mL) scale stirred tank bioreactors, and microfludics integrated micro-scale bioreactors, and their potential for practical application in QbD-driven HTP process development are also critically appraised. The overall aim of such technology is to rapidly gain process insights, and since the analytical technology deployed in HTP systems is critically important to the achievement of this aim, this rapidly developing area is discussed. Finally, general future trends are critically reviewed.