Exploration and evaluation of modular concepts for the design of full-scale pharmaceutical manufacturing facilities.

The design of biopharmaceutical processes is predominantly driven by the domain of experimental process design. This approach can be further improved by combining multiple domain information such as experiments, unit models, and flowsheet models. Approaches consisting of methods and flowsheet models provide the framework for exploring, analyzing, and ultimately evaluating the combinatorial space of all possible designs within the molecule-to-manufacturing value chain. In recent years, modular process designs are of interest in the pharmaceutical industry because of the shift toward multiproduct, mutiprocess processes. Therefore, a systematic approach for how to evaluate the utilization of the modular plug-n-play concept provides metrics that can propel modular design from a viable design alternative to the selected alternative for full-scale manufacturing. The objective of this paper is to present such an in silico approach for the evaluation of modular designs. The approach is presented as a systematic method and then, is exemplified through the manufacture of an active pharmaceutical ingredient (API). The application of the method shows how to transition from a typical design-for-purpose design alternative to a modular design through the utilization of data, modeling, simulation, and uncertainty/sensitivity analyses for quantification of various selection metrics such as process robustness and flexibility.

Toward in silico CMC: An industrial collaborative approach to model-based process development.

The Third Modeling Workshop focusing on bioprocess modeling was held in Kenilworth, NJ in May 2019. A summary of these Workshop proceedings is captured in this manuscript. Modeling is an active area of research within the biotechnology community, and there is a critical need to assess the current state and opportunities for continued investment to realize the full potential of models, including resource and time savings. Beyond individual presentations and topics of novel interest, a substantial portion of the Workshop was devoted toward group discussions of current states and future directions in modeling fields. All scales of modeling, from biophysical models at the molecular level and up through large scale facility and plant modeling, were considered in these discussions and are summarized in the manuscript. Model life cycle management from model development to implementation and sustainment are also considered for different stages of clinical development and commercial production. The manuscript provides a comprehensive overview of bioprocess modeling while suggesting an ideal future state with standardized approaches aligned across the industry.

New Vistas in Chemical Product and Process Design.

Design of chemicals-based products is broadly classified into those that are process centered and those that are product centered. In this article, the designs of both classes of products are reviewed from a process systems point of view; developments related to the design of the chemical product, its corresponding process, and its integration are highlighted. Although significant advances have been made in the development of systematic model-based techniques for process design (also for optimization, operation, and control), much work is needed to reach the same level for product design. Timeline diagrams illustrating key contributions in product design, process design, and integrated product-process design are presented. The search for novel, innovative, and sustainable solutions must be matched by consideration of issues related to the multidisciplinary nature of problems, the lack of data needed for model development, solution strategies that incorporate multiscale options, and reliability versus predictive power. The need for an integrated model-experiment-based design approach is discussed together with benefits of employing a systematic computer-aided framework with built-in design templates.