(76b) Quality-by-Control (QbC) Technologies for Pharmaceutical Process Development

The advent of process analytical technologies (PAT) more than a decade ago has brought the applications of advanced control of pharmaceutical manufacturing processes in the realm of possibility. The role of advanced feedback control concepts in improving the performance of batch processes, as well as enabling technologies in the paradigm shift from batch to continuous manufacturing will be corroborated. Examples how advanced control can be used for the improved production of pharmaceutical particulates will be provided, with application to both continuous drug substance and drug product manufacturing. Novel control approaches for integrated continuous crystallization and wet milling systems will be presented that can produce crystalline materials with tailored maid properties with excellent consistency. The role of rigorous mathematical modelling in the systematic optimal design, start-up and control of continuous crystallization processes to achieve and maintain the desired controlled stage of operation will be illustrated through examples for both cascade of mixed suspensions mixed product removal (MSMPR) as well as plug flow crystallization systems. Anti-fouling control (AFC) will be presented as an illustrative example demonstrating how active feedback control can be the key enabling technology for the implementation and smooth operation of continuous crystallization processes. The application of a systematic framework for the design of hierarchical control systems for continuous tablet production will also be described. A novel view for implementing continuous drug manufacturing processes that are based on spatially distributed control of various particle formation processes within a single continuous plug flow system, rather than the integration of individual unit operations, will be presented. The system uses spatially distributed antisolvent addition, heating/cooling cycles and/or binder/excipients addition to control the individual mechanisms of nucleation, growth and spherical agglomeration to produce particles with controlled internal and external size and micromeritic properties. The talk intends to provide motivating examples of the next stage of innovation in pharmaceutical manufacturing, illustrating the potential benefits of the new quality-by-control (QbC) framework in improving product quality and process efficiency while reducing costs and time-to-market.