The development of a relative potency assay to support biologic drug products requires significant budget, resources, and time to achieve the desired quality for release testing. Potency assays ensure safe and efficacious products are delivered to patients, and cell-based bioassays require 1) a relevant and permissive cell line, 2) ability to demonstrate the drug’s mechanism of action (MoA), and 3) quantitative end point. Cell line engineering can achieve these requirements and simplify the MoA detection in a reporter gene system. Here we describe a case study where an engineered reporter gene cell line was used to develop and qualify a relative potency assay within Analytical Development. A cross-over study was successfully performed to transition assay platforms during an ongoing Phase I GMP stability study.