From Bench To Billions: Facilitating Scale-Up Of Adherent Cultures For Cell And Gene Therapies

Given the promise and potential of cell and gene therapies (CGT) across a variety of disease states, it's no secret that the market will demand more of them in the years ahead. The challenge is how to generate the number of cells required (which can amount to tens to hundreds of billions) with limited resources and time. The move toward allogeneic, "one-to-many" programs has required scale-out and scale-up from the bench at a breakneck clip. One adult patient, for example, might require hundreds of millions of cells in a single therapeutic dose. Multiply that by hundreds of patients enrolled in a clinical trial, and the demand can become bewilderingly large for a seed train that originates from just one cryovial.

As life scientists and process engineers know, there are nuances to biomanufacturing that make achieving this kind of scale difficult in the lab. Cell type is one factor. If the cells of interest are attachment dependent, such as induced pluripotent stem cells (iPSC), there are specific advantages to using an attachment-friendly adherent cell culture platform for cell expansion.  These choices can have operational impacts on manufacturability, from footprint, labor and cost of goods sold to process control and GMP compliance.

Underlying all of this is the fact that cells are living things that are prone to unpredictability, stress, damage, and death. Scale requires getting to a level of cell production that's compatible with a clinical application without sacrificing the phenotype or quality of the cells or losing their potency over time. For example, some types of stem cells may only divide a handful of times before they lose the stemness properties that make therapies effective.

Maintaining culture in adherent conditions at scale is possible with forethought into workflow integrations, automation, and platform choices in developing a manufacture-ready seed train for these powerful cultures. This guide explores what researchers should consider when they are creating a risk-mitigating adherent culture process for cell and gene therapy scale-up.