Making Cell Therapies Work for Patients: Defining and Driving Label-Free Critical Quality Attributes

Manufacturing of cell therapies includes a persistent challenge shared by allogeneic and autologous approaches, for a range of target disease and injury indications. What are the attributes of the cell therapy product that map to quality, and more specifically to identity, potency, and therapeutic efficacy? Critical quality attributes can be used to enable real-time and endpoint product release, but also have the potential to enable process analytics that adapt to promote those CQAs during production. Imagine the capacity to monitor and moderate those attributes during production, without the need for labeling cells and with the throughput that qualifies all the cells in the final product. Here we will discuss opportunities and progress in identifying label-free CQAs, including those based on biophysical attributes of the cells, with an eye toward in-line approaches facilitating adaptive culture and real-time release. We will focus on mesenchymal stromal cells for regenerative medicine and genetically modified T cells for blood cancers, to illustrate concepts and technologies that complement current at-line and endpoint product characterization.