Real-time supervision of batch operations during the progress of a batch run offers many advantages over end-of-batch quality control. Process monitoring, quality estimation, and fault diagnosis activities are automated and supervised by embedding them into a real-time knowledge-based system (RTKBS). Interpretation of multivariate charts is also automated through a generic rule-base for efficient alarm handling and fault diagnosis. Multivariate statistical techniques such as multiway partial least squares (MPLS) provide a powerful modeling, monitoring, and supervision framework. Online process monitoring techniques are developed and extended to include predictions of end-of-batch quality measurements during the progress of a batch run. The integrated RTKBS and the implementation of MPLS-based process monitoring and quality control are illustrated using a fed-batch penicillin production benchmark process simulator.