ABSTRACT: Open Process Automation (OPA) and Digital Twin (DT) technologies show great promise to reduce risk, downtime, and energy consumption, while improving safety and efficiency in manufacturing systems. OPA defines a reference architecture for constructing scalable, reliable, interoperable, and secure automation systems with products from multiple vendors as a single, cohesive system. DTs are purpose-driven dynamic digital replicas of physical assets, processes, systems, or products. Both technologies enable increased options and competition for accelerating future innovation. However, there are significant challenges to adopting these technologies, including “plug-and-play” interoperability, access to data, access to equipment, and the combination of different DTs for system-wide improvements. This paper demonstrates and evaluates a DT Framework solution for performance monitoring in process manufacturing systems that aims to avoid unplanned downtime, a prevalent challenge that pressures profitability in manufacturing. The DT framework is built and demonstrated through an OPA testbed system that allows seamless gathering and analyzing of data from a process manufacturing line. The proposed DT framework solution provides guidelines to develop, test, and evaluate new system-wide DT solutions without interrupting production operations and without costly R&D investments.