Background & Aim Cell and gene therapies show promise in providing new therapeutic strategies for a wide range of indications. Advancements in induced pluripotent stem cell (hiPSC) technologies have substantially expanded access to many human cell types to accommodate the future demand for such therapies. However, the direct utilization of standard cell manufacturing equipment and methods in the differentiation and manufacture of iPSC-derived cells can face significant challenges in obtaining the necessary production scales, quality standards and high reproducibility between batches for cost-effective cell therapy research and clinical application. Currently, the development and production of iPSC-derived cell types is often performed in a small-scale culture unsuitable for robust generation of a large number of cells. Using the example of cell-based therapy for heart failure, it is estimated that 109 cells are required per patient with a target population potentially requiring thousands of doses per year, as much as 1011 - 1014 cells. Stirred-tank bioreactors have emerged as promising culture systems for large-scale cell manufacturing from hiPSC sources. These systems allow full automation and conduction in closed systems that can be monitored and maintained at defined physiochemical levels, resulting in cultures with comparable characteristics from batch to batch. Closed-system, parallel processing with increased automation is also critical to minimize error and contamination from human interaction with cell products. Methods, Results & Conclusion Ncardia has established a controlled stirred-tank bioreactor platform that is shown to routinely yield high numbers of hiPSC-derived cardiomyocytes and additional cell models that are currently used in cell therapy, safety and efficacy applications. Using a Quality by Design approach, we demonstrate a robust and controlled process for large-scale manufacturing (>3 × 1010) of iPSC-derived cardiomyocytes to a purity of >95% in a serum-free protocol. The bioreactor-derived cells are shown to be a relatively mature model recapitulating a human cardiomyocyte's contractile and electrophysiological profile. We demonstrate the implementation of a flexible process development workflow comprised of state-of-the-art bioreactor systems that allows for optimization of processes at 15 mL scale, validation of promising conditions at mid-scale (100 - 250 mL) and manufacture from a diverse set of hiPSC lines to yield the required scale in the tens of billions.