In-use physicochemical stability studies are aimed at ensuring patient safety during the clinical administration of drug products. These studies are intended to demonstrate drug product stability and compatibility with the administration process by mimicking recommended in-use hold-times and clinical administration methods. There is limited health authority guidance on specific in-use testing practices. As such, current strategies should be guided by factors that can impact potential critical quality attributes (pCQAs) including 1) country or region-specific expectations for clinical administration, 2) anticipated drug product hold-times and administration practices during clinical use, and 3) required administration materials in the fluid path. For cell therapies in particular, in-use stability studies are complicated by the fact that the administered cells are living drugs that require diverse and potentially complex methods to relate product CQAs to clinical outcomes. Here, we discuss specific challenges with the administration of cell therapies and strategies to guide in-use testing practices for this new therapy.