IMPLEMENTATION PROCEDURE OF AN ADVANCED SUPERVISORY AND CONTROL STRATEGY IN THE PHARMACEUTICAL INDUSTRY
Abstract This paper describes the different steps followed in implementing a temperature controller and a supervisory controller in a Supervisory Control And Data Acquisition (SCADA) system to control a 60 and 160 l reactor in a pharmaceutical factory. These reactors are used to produce the initial quantities of drugs needed to perform clinical tests. The chemical reactions involved are often changed (several times a week). The different steps of the project will be presented: • design of a new heating–cooling system, • design of the predictive and Supervisory Control Algorithm (SCA), • connection of the SCA to the SCADA system, • experimental validation according to Good Manufacturing Practice (GMP). 
This SCA has been in daily use as the standard control system for more than 2 years.
Real-time Exceptional Events Management for a Partial Continuous Dry Granulation Line
PurposeThis study focuses on the implementation of a real-time exceptional events management (EEM) framework on a pharmaceutical manufacturing process to demonstrate its efficacy in detecting, diagnosing, and mitigating incipient exceptional events on a continuous process.MethodsThe real-time EEM framework integrates signed directed graph and trend analysis methods for diagnosis. Additionally, fast Fourier transform analyses are performed via a parallel moving window to detect oscillatory behavior. The EEM framework is demonstrated on a partial continuous dry granulation line consisting of two feeders, blender, and roller compactor and is shown to be capable of incipient fault diagnosis. In addition, simultaneous occurrences of different exceptional events are considered in this study, and a protocol is developed for multiple fault identification.ResultsThe framework is observed to detect, diagnose, and offer mitigation strategies within 10 s of event inception for the following cases: (1) simultaneous occurrences of different exceptional events in a particular, isolated, equipment, (2) simultaneous occurrences of different exceptional events spanning multiple equipment, and (3) consecutive occurrences of events. Additionally, the EEM framework is capable of limiting the progression of exceptional events originating in an upstream equipment, thus ensuring minimal to no propagation of exceptional events. Once an exceptional event has been determined, mitigation strategies are retrieved from the knowledge base and are either presented to the operator as an advisory or automatically executed to restore normal operating conditions.ConclusionsThe real-time EEM framework is demonstrated to effectively detect, diagnose, and mitigate known exceptional events using built-in process knowledge. In addition, a protocol for handling multiple fault identification is successfully demonstrated on the partial continuous dry granulation line. Finally, quick and effective remediation of an exceptional event as it begins is shown to prevent the propagation of its effects downstream, thus reducing subsequent deviations across the continuous line.
A new heating-cooling system to improve controllability of batch reactors
The mathematical modelling and the development of a numerical simulator of a pilot-plant batch reactor are presented. In this paper, dynamic simulation and advanced control strategy are given. This work presents the development and characterisation of a multipurpose batch reactor with a variable heating/cooling structure for temperature control. This strategy is based on the use of the thermal flux as the manipulated variable. The controller (the Generalised Predictive Controller) computes at each sampling time the thermal flux to be exchanged with the thermal fluid flowing in the jacket to achieve the desired reactor temperature profile. This information is then used to select the thermal fluid on the basis of the maximal and minimal thermal flux capacities computed on-line for each utility. This methodology allows to overcome the discontinuities due to utility fluid switching frequently encountered during the batch reactor operation.