What product limits have you found with continuous with either product type or demand?

Answer

We don’t see many product related limits when using a continuous process scheme compared to a traditional fed-batch process. In fact, continuous manufacturing can accommodate a wide variety of molecules – including mAbs, fusion proteins, growth factors, recombinant enzymes, etc. – many of which could not be produced in other cell culture modes (such as fed-batch) due to product stability issues. The only limit we’ve observed is that some specific molecules may have product retention issues during continuous harvest when using certain types of hollow fiber filter (HFF)-based cell separation devices due to the proteins’ large molecule weight or other unique characteristics of the molecule. The challenge can usually be addressed by screening of different membrane materials and evaluation of membrane pore size and membrane area in the HFF system during process development. Alternatively, other cell retention devices with different mechanisms of action can be also considered, like those based on gravitation (inclined cell settlers, centrifugation) or acoustic resonance systems.

In addition, high productivity can be achieved with a reduced manufacturing footprint compared to fed-batch systems and the facility can be easily scaled-out to manufacture large quantities of product with reduced cost. For those products with relatively low demand, utilizing continuous processing can still be cost-effective because utilizing a well-developed and universal platform would require minimal process development and scale-up work.