Reducing a major cost burden of therapeutic cell manufacturing by selectivelyremoving toxic culture byproducts to allow recycling of media

ABSTRACT:The tremendous cost of cell-based therapies manufacturing is the significant threat to the success of cell/gene therapy treatments. The cell culture medium alone can contribute to around 30-40% of the Cost of Goods (COGs). This is because, the current cell culture methods require frequent and complete media replacement in order to remove toxic metabolites from culture. This practice of completely replacing the medium with fresh medium adds significant expense and contributes to unnecessary waste. Restoring nutrient, osmotic, and pH balance need not require replacement of the entire culture medium volume. At production scale, some version of medium recycling will be required to reduce waste and overall cost of manufacturing. The aim of the current study is to develop a cost-effective media filtration system using coconut-shell derived activated carbons (CS-AC) that can selectively remove two important toxic metabolites such as lactic acid and ammonium from cell culture medium. With such filtration system, metabolic waste products can selectively be removed, non- metabolized components like buffers, and growth factors can be retained, and the depleted nutrients like sugars and amino acids can be replenished as they are consumed by the cells. Determining the level of recycling that is achievable by this filtration technology for each component of the culture medium requires a significantly more complex analysis informed by empirical data from spent medium analysis.The ultimate goal of this study is to utilize this filtration technology and develop a commercial grade single-use filtration device by embedding the AC into cellulose matrix or neutral-grade resins. The application of the new filtration device to remove toxic metabolites from spent culture medium will transform the current approaches being investigated for COG reduction during cell based therapeutic manufacturing. Such a filtration system holds a great promise for affordable cell/gene therapy treatment possibilities, and is expected to have a strong economical impact on clinical medicine.Narrative: The study deals with design and development of a filtration technology for depleting toxic metabolites from spent culture media. The filtered media with growth supporting factors will be recycled back to the culture, potentially eliminating frequent culture media changes and reducing the COG for cell/gene therapy manufacturing. The ultimate goal of this study is to utilize this filtration technology and develop a commercial grade single-use filtration device.