At what scale would you recommend moving into manufacturing with microcarriers?

Answer

The advantages of moving into microcarrier based culture can be realized at relatively small scale. Operation of a bioreactor with a 2.5L working volume using 2 g/L of Corning Dissolvable Microcarriers equates to approximately 25000 cm² of available surface area for cell culture while occupying a small footprint of bench space. The equivalent to this in multi-layer flasks requires either many individual flasks or a few large units that both involve manipulation challenges and labor. A move away from static multi-layer flasks to microcarriers would be ideal, as long as sophisticated monitoring, control, and automation are desired, asthe ability to maintain set points at optimum ranges can impact yield and target product profile. Having these data fits nicely into Quality by Design approaches and generates a significant amount of data for process understanding and control. Additionally, bioreactor culture greatly simplifies sampling of a culture as it can be performed less invasively with reduced aseptic risk. The data generated from a single bioreactor sample are representative of the whole culture as opposed to potential differences between flasks. Regulatory testing requirements may dictate that each vessel have some level of testing (e.g. cell count, metabolite, filter-integrity testing) which is simplified in bioreactor based cultivation. Lastly, labor costs for sampling as well as consumable costs can be reduced, including media per unit of surface area. So the scale that triggers a change to microcarriers will largely depend on how you weigh the benefits of bioreactor technology.