Flexible Modular Platform for Cell Manufacturing

Expansion culture of stem cells, which is the most critical steps to realizethe transplant of cells for cell therapy and regenerative medicine, areaccomplished regarding the safety and cost-saving under the asepticenvironment in the cell processing facility (CPF). In this line, thetriple issues of safe, cost-saving and secure (3S) are desired for theindustrialization, in large part because of keeping the cost down forcell processing and stability of the final products. Given that the serialprocesses may affect the quality of the cells, the processes in appropriateCPF is expected not only to maintain an aseptic environment but alsoto provide stable processing. The design for manufacturability (DFM) is long known to be the general engineering approach for the designingproducts in an easy to manufacture manner. This concept exists inalmost all engineering disciplines, but the implementation differs widelydepending on the manufacturing technology. The cell production hasmany features in processes, I would like to make the concept of cellmanufacturability as follows; Manufacturing design of cell-basedproducts in such a way that they are easy to manufacture through simple, safe and efficient (cost-saving) process with stable product quality andsecure to customer (especially patients) by considering transpiration andhospital preparation outside factory. This concept can lead to facilitationof the consistency and robustness for the process and the reduced costfor the cell manufacturing. The system consists of input and output forthe process. There are several fluctuations derived from extrinsic noises(environmental errors) against the system, input quality such as startercells and materials (medium, reagents, vessel and pipet etc.), andintrinsic disorders (in-process errors). Especially, intrinsic disorders causethe difficulty to make consistency and robust process for stable qualitybecause the cells have uncertainty accompanied by time-dependent andtardive properties. Therefore, environmental, material, and operationalstandardizations are required to realize a consistent process. The cellprocessing in a closed aseptic chamber can be done using a cell processingisolator system, which can reduce the equipment and maintenance/operation costs and also provide a reliable aseptic environment. A newdesign of manufacturing facility has been suggested based on the isolatortechnology. Our proposal system is the flexible modular platform (fMP)that may be seen as the individual aseptic modules that can connect anddisconnect between modules (or pods) flexible with keeping the asepticenvironment in each module (or pods). Such approach can result in thecompactness of aseptic processing area and quick change-over for multipurposesand patients. To efficiently implement such fMP technology, aninterface that can be aseptically detached and attached from one moduleto another is required, responding to diversified requirements for thecell processing. The interface of the double door system is developedfor the flexible connections between modules with shortening of thedecontamination process. Thus, our attempts are concluded to build anadvanced culture system employing isolator technology as well as largescaleculture in suspension of iPSCs, and the adaptation of the fMP inCPF will lead to easy installation of the new modules for production lineaddition and/or revision through the clinical phases as well as commercialproduction, which contributes to the reduction of production costs.

کلیدواژه ها:

Stem cells ، Cell processing facility ، Cell manufacturability ، Flexible Modular Platform ، Automation