Next Ten Years
Single-use technology for the production of protein therapeutics is not expected to continue to grow as rapidly. Standardization activities, however, for single-use systems should be carried out and efforts made to overcome the existing limitations (pressure, flow rates, mixing, temperature control, in-process monitoring, oxygen/CO2 stripping rates, leachables/extractables).
Sensors for relevant process parameters as well as improved equipment for depth-, ultra-, and diafiltration, chromatography, and filling at large scale are already under way.
If all these changes are implemented, we will be a step closer to a complete single-use production facility and to the concept of a “single-use factory in a box.”
The extent to which 4 or 5 m3 single-use bioreactors are necessary remains questionable. For most new protein therapeutics (vaccines, personalized antibodies) 1 and 2 m3 sizes are sufficient. The difficulty lies not in the development of a 4 or 5 m3 single-use bioreactor but in its handling and storage.
New-generation biotherapeutics (based on autologous or allogeneic human stem cells or T cells) will largely determine the further development of single-use technology. About 40 cell-therapy products are currently on the market and more than 200 are at the clinical-research stage. For the manufacture of cell-therapy products to be commercially successful, innovative equipment and new technologies are required.
Due to the production demands of cell therapeutics, single-use systems are essential. The manufacture of cell therapeutics is focused on the generation of bioactive cells that are directly infused into a patient. For cell-based therapeutics it is assumed that culture volumes in upstream processing are smaller (0.01 to 1 m3) than those for protein-based products.
GMP-compliant platform solutions with single-use bioreactors that allow efficient expansion and/or differentiation of adherent and suspension cells are also needed.
Open centrifugation tubes and blood-processing equipment, which have to date been used in already certified processes, are not suitable for the downstream processing of large amounts of cell culture broth. Solutions, which include automation of the filling process and cryopreservation at large scale, are required.
Finally, single-use systems for nonmammalian cell applications (insect, microbial, plant cell-derived) to generate niche products are on the horizon. Single-use systems are also expected to become important in areas with high cleaning and safety demands in industrial biotechnology.