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

点击翻译按钮获取中文摘要

Project Summary / Abstract Over the past five years, this Purdue University team has been collaborating with colleagues at Rutgers University 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 for Structured Organic Particulate Systems. In parallel, the PI and Purdue co-workers have investigated CM approaches to small molecule API manufacture at micro and intermediate scales. This work has demonstrated the essential roles of process modeling, process analytical technology, active process control, intelligent process monitoring, material tracking and real time risk assessment. Moreover, current work is showing how these components must be linked through an integrated data management and informatics infrastructure in order to achieve the desired Industry 4.0 functionalities. While CM is an important development for the pharmaceutical industry, it is not a universal solution that meets all manufacturing needs, either technically or economically: often hybrid batch-continuous or fully batch modes 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 and thus significantly improve quality and reduce cost of medicines. The goal of this proposal is to expand the research on CM to develop and demonstrate a framework for the design and operation of batch and hybrid small molecule manufacturing systems. This will be achieved through five aims: Aim 1: Development of Pharmaceutical Model Library for small molecule and oral drug product manufacture Aim 2: General framework for the optimal synthesis of processes for small molecule-based API and product manufacture, encompassing the spectrum from batch to fully continuous processes Aim 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 high volume/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 industry as 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 the pharmaceutical sector as well as the demonstration of the framework for systematic design and operation of processes for several specific drugs, including the effects of scale. The case studies will serve to inform and promote innovative manufacturing practices across the numerous batch and hybrid batch-continuous facilities existing worldwide. Moreover, by complementing the progress made in CM, it will enable the FDA to develop effective guidelines on the application of Industry 4.0 functionalities across the industry.