Abstract:Machine learning (ML) has significantly contributed to the development of bioprocess engineering, but its application is still limited, hampering the enormous potential for bioprocess automation. ML for model building automation can be seen as a way of introducing another level of abstraction to focus expert humans in the most cognitive tasks of bioprocess development. First, probabilistic programming is used for the autonomous building of predictive models. Second, machine learning automatically assesses alternative decisions by planning experiments to test hypotheses and conducting investigations to gather informative data that focus on model selection based on the uncertainty of model predictions. This review provides a comprehensive overview of ML-based automation in bioprocess development. On the one hand, the biotech and bioengineering community should be aware of the potential and, most importantly, the limitation of existing ML solutions for their application in biotechnology and biopharma. On the other hand, it is essential to identify the missing links to enable the easy implementation of ML and Artificial Intelligence (AI) solutions in valuable solutions for the bio-community. We summarize recent ML implementation across several important subfields of bioprocess systems and raise two crucial challenges remaining the bottleneck of bioprocess automation and reducing uncertainty in biotechnology development. There is no one-fits-all procedure; however, this review should help identify the potential automation combining biotechnology and ML domains.