Current potential bioprocess solutions for the scaleup of adherent cells include cell stacks, robotic flask handling, packed-bed culture, hollow-fiber bioreactors, and microcarriers or aggregate culture in stirred tanks.
Cell stacks and robotic flask handling can increase the total surface area in culture but do not remove the open events (e.g., taking the top off a T-flask and exposing it to potential contamination) from the process or eliminate the wasteful feeding strategies inherent to flask-based systems. Packed-bed systems have traditionally been used for protein and antibody production and are not designed for the efficient recovery of cells.
The growth of cells on microcarriers can result in mechanical damage to the cells and difficulty removing the microcarriers from the cell product. Maintaining the proper aggregate size and cell viability in stirred tank bioreactors can require the use of enzymatic or mechanical methods that can damage the cells.
Automation has been defined as a handoff of tedious and routine tasks to more efficient and reliable machines. Progress in bioprocess automation has been slow because many of the current instruments are not up to the task.
Automation of a flask-based manual cell-culture process can solve many of the problems of scaleup. A closed system reduces the number of open events and improves sterility. Automation can reduce labor costs and improve throughput. Improved product quality and reduced variability can lead to better regulatory compliance and contain cost.
Automation of process steps eliminates human inconsistencies and errors while maintaining optimized culture conditions across multiple manufacturing sites. Finally, automation can aid in regulatory compliance and improve product comparability by locking in process changes.