Bioprocess monitoring and computer control: key roots of the current PAT initiative.

This review article has been written for the journal, Biotechnology and Bioengineering, to commemorate the 70th birthday of Daniel I.C. Wang, who served as doctoral thesis advisor to each of the co-authors, but a decade apart. Key roots of the current PAT initiative in bioprocess monitoring and control are described, focusing on the impact of Danny Wang's research as a professor at MIT. The history of computer control and monitoring in biochemical processing has been used to identify the areas that have already benefited and those that are most likely to benefit in the future from PAT applications. Past applications have included the use of indirect estimation methods for cell density, expansion of on-line/at-line and on-line/in situ measurement techniques, and development of models and expert systems for control and optimization. Future applications are likely to encompass additional novel measurement technologies, measurements for multi-scale and disposable bioreactors, real time batch release, and more efficient data utilization to achieve process validation and continuous improvement goals. Dan Wang's substantial contributions in this arena have been one key factor in steering the PAT initiative towards realistic and attainable industrial applications.