Pharma 4.0

Industry 4.0 offers potential benefits for improving pharmaceutical manufacturing in terms of flexibility, costs, quality, and safety.  Recently, Quality by Design (QbD), PAT and Real-Time Release Testing (RTRT) initiatives to improve product design and manufacturing processes in the pharmaceutical industry have become prominent. Moreover, the microreactors used in continuous manufacturing allow reaction to take place on a much shorter temporal scale, making it easier to quench reactions, and avoiding adverse bi-products. QbD recommends systematic prospective analysis of product and process characteristics when the product is being designed. RTRT and PAT measure and control Critical Process Parameters (CPP) and their relation to Critical Quality Attributes (CQA) in a similar way to ‘CAM’, which is widely used in common production systems in other industries. This work proposes a Cyber-Physical-based PAT framework for adoption of Smart Pharmaceutical Manufacturing Systems. The framework is based on multi-smart agents in multiple levels. The implementation of the system is thoroughly examined by using UML system modeling tools. We applied CPbPAT on a manufacturing case study that is developed by FDA to demonstrate the implementation of manufacturing technologies in the pharmaceutical industry. In the case study, we simulated CPbPAT under normal and abnormal manufacturing conditions and examined how CPbPAT responds to unexpected changes. We used latency to measure the relative response time of the system for OoR process parameters. Given that the simulation was done on a particular prototype test setting, latency times could be improved by increasing the computation power and the efficiency of the agent-based system. The case study also confirms that the system is robust while working without unnecessary interventions when no disturbance arises. The system is able to adapt itself to multiple OoR process parameters.