Risk-based process synthesis and Industry 4.0 framework for pharmaceutical manufacturing processes

Project Summary / Abstract Over the past five years, this Purdue University team has been collaborating with colleagues at RutgersUniversity to investigate the computational and experimental infrastructure for continuous manufacturing (CM)of solid oral dosage products. This work has built on a decade of research under the NSF supported Center forStructured Organic Particulate Systems. In parallel, the PI and Purdue co-workers have investigated CMapproaches to small molecule API manufacture at micro and intermediate scales. This work has demonstratedthe essential roles of process modeling, process analytical technology, active process control, intelligent processmonitoring, material tracking and real time risk assessment. Moreover, current work is showing how thesecomponents must be linked through an integrated data management and informatics infrastructure in order toachieve the desired Industry 4.0 functionalities. While CM is an important development for the pharmaceutical industry, it is not a universal solution thatmeets all manufacturing needs, either technically or economically: often hybrid batch-continuous or fully batchmodes can be advantageous. Moreover, given the major investment in existing batch facilities in the generic\manufacturing sector, there is an unmet need to bring Industry 4.0 functionalities to those manufacturers andthus significantly improve quality and reduce cost of medicines. The goal of this proposal is to expand theresearch on CM to develop and demonstrate a framework for the design and operation of batch and hybrid smallmolecule manufacturing systems. This will be achieved through five aims:Aim 1: Development of Pharmaceutical Model Library for small molecule and oral drug product manufactureAim 2: General framework for the optimal synthesis of processes for small molecule-based API and productmanufacture, encompassing the spectrum from batch to fully continuous processesAim 3: Development of an Industry 4.0 real-time process management framework (RTPM).Aim 4: Demonstration of these technologies using several case-studies including high cost/low volume and highvolume/low cost generic drugs at three different scales (lab, pilot and industrial)Aim 5: Development of instructional modules for conducting training programs for both FDA staff and industryas well as web-based access to tools and cases studies via pharmaHUB. This work will result in the development of the tool set necessary to implement Industry 4.0 across thepharmaceutical sector as well as the demonstration of the framework for systematic design and operation ofprocesses for several specific drugs, including the effects of scale. The case studies will serve to inform andpromote innovative manufacturing practices across the numerous batch and hybrid batch-continuous facilitiesexisting worldwide. Moreover, by complementing the progress made in CM, it will enable the FDA to developeffective guidelines on the application of Industry 4.0 functionalities across the industry.