History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance

Biological systems are typically composed of highly interconnected subunits and possess an inherent complexity that make monitoring, control and optimization of a bioprocess a challenging task. Today a toolset of modeling techniques can provide guidance in understanding complexity and in meeting those challenges. Over the last four decades, computational performance increased exponentially. This increase in hardware capacity allowed ever more detailed and computationally intensive models approaching a "one-to-one" representation of the biological reality. Fueled by governmental guidelines like the PAT initiative of the FDA, novel soft sensors and techniques were developed in the past to ensure product quality and provide data in real time. The estimation of current process state and prediction of future process course eventually enabled dynamic process control. In this review, past, present and envisioned future of models in biotechnology are compared and discussed with regard to application in process monitoring, control and optimization. In addition, hardware requirements and availability to fit the needs of increasingly more complex models are summarized. The major techniques and diverse approaches of modeling in industrial biotechnology are compared, and current as well as future trends and perspectives are outlined.