This technical article describes ongoing work that is focused on developing and implementing a process-development methodology that applies state-of-the-art automated sampling technology with on-line and at-line cell-state monitoring technologies—both novel and existing—to bioreactor processes for biotherapeutics manufacturing. The ultimate goal of this work is to improve cell and protein production by optimizing bioreactor processes using real-time data-integration technologies. Efforts are described to develop integrated hardware and software technologies for biotherapeutic manufacturing to reduce risk and optimize fed-batch and perfusion processes.