Title: Dissolvable 3D macroporous microcarrier based large-scale manufacturing system for cell and gene therapy
Abstract:
Researchers in the field of cell and gene therapy have long faced the daunting task of efficiently and extensively expanding cells. Overcoming the limitations of the 2D planar culturing system has been a significant challenge. However, we have made a groundbreaking advancement by introducing a revolutionary automated closed large-scale cell production platform. This platform utilizes 3D TableTrix microcarriers to cultivate adherent cells,effectively addressing the major drawbacks of the 2D planar culturing system. 3D TableTrix is a novel GMP-grade microcarriers registered as pharmaceutical excipient under Drug Master Files with the United States (U.S.) Food and Drug Administration (FDA, DMF #35481) and the Chinese Center of Drug Evaluation (CDE, F20200000496 and F20210000003). These microcarriers are macroporous with high culture surface area and fully dissolvable for efficient cell harvest at a recovery rate of 98.6±0.1%. To scale up, different models of stirred-tank bioreactors (vivaSPIN) are used for cell expansion on 3D TableTrix microcarriers. We demonstrated the potential of our production platform with umbilical cord-mesenchymal stem/stromal cells (UCMSCs), as the broad potential of mesenchymal stem cells (MSCs) in regenerative medicine is widely recognized. A three-stage expansion was conducted with 1 L, 5 L and 15 L bioreactors. A final yield of 2.09×1010 MSCs with an overall expansion factor of 1975 within 13 days was achieved. To complete the production process, the cells were harvested, concentrated, washed and formulated automatically with the closed cell processing system, vivaPREP PLUS. A fully automated and closed fill and finish system, vivaPACK, was then used to aliquot these cells into cryobags. Cells harvested from 3D microcarrier culture retained their immunophenotypic characteristics, tri-lineage differentiation potential, genome stability and low indications of senescence phenotype, among a series of quality tests performed. Results indicated that there was no significant difference with cells cultured by the conventional 2D planar method. Residuals of microcarrier and microcarrier dissolution reagent were also evaluated to be within safety limits. The potential of 3D TableTrix microcarriers were further testified with other adherent cells commonly used in cell and gene therapy, such as HEK293T and Vero cells. After serial expansion in vivaSPIN bioreactors, cell concentration for HEK293T cells reached a maximum of 1.02×107 cells/ml, while Vero cells expanded to 1.07×107 cells/ml. This study introduces a bioprocess engineering platform that leverages on macroporous and dissolvable 3D TableTrix microcarriers to successfully achieve large-scale production of adherent cells relevant to the cell and gene therapy industry.
Audience Take Away Notes :
- The audience will be able to learn about a new dissolvable microcarrier that could be used for expansion and efficient harvesting of adherent cells
- The audience would then know that MSCs could be efficiently expanded in an automated manner in compliant to GMP standard, which could help them improve their cell manufacturing capability.
- This is a practical design of an automated and efficient cell manufacturing facility.
