Real-Time Monitoring and Control of Continuous Pharmaceutical Manufacturing

Yuma Miyai, Virginia Commonwealth University


The pharmaceutical industry has traditionally operated based on the batch manufacturing principles that often lack reliability, agility, and robustness in the manufacturing of drugs. This practice poses a potential public health risk in the form of drug shortages in which the modernization of pharmaceutical manufacturing, as encouraged by the Food and Drug Administration (FDA), aims to promote efficient and flexible manufacturing practices that reliably produce high-quality drugs while reducing the cost. To achieve this goal, continuous pharmaceutical manufacturing has gained interest in industry, academia, and regulatory agencies for its benefits over the traditional batch manufacturing. These benefits include increased process efficiency and safety as well as reduced process time, waste, space requirements, and operational costs. In addition to continuous manufacturing, process analytical technology (PAT), process modeling, and process automation and control also play a central role in realizing this goal.

The research conducted in this dissertation addresses the need to develop an advanced pharmaceutical manufacturing platform for active pharmaceutical ingredient (API) synthesis to facilitate the reliable production of high-quality APIs. This platform allows the digitalization of continuous manufacturing to achieve real-time process monitoring and control to ensure product quality. The research aims are divided into three components: 1) implementation of PAT for real-time process monitoring, 2) development of continuous API synthesis process where PAT, DOE, and process modeling are utilized to gain in-depth process understanding, and 3) construction of an advanced manufacturing platform and digitalization of continuous manufacturing where process automation and online process modeling is achieved.

In addition to the research effort made toward the advancement of pharmaceutical manufacturing, the development of an academic course focusing on the pharmaceutical engineering concepts is discussed. This graduate-level laboratory course addresses the growing need for a next generation of researchers in design, development, and manufacturing of pharmaceutical products. The course materials are designed to introduce students to the theoretical concepts as well as hands-on experience and engineering techniques that are critical in the pharmaceutical process development and manufacturing.

This work has contributed in the advancement of pharmaceutical manufacturing through the investigation of an advanced pharmaceutical platform as well as the establishment of an academic training material, therefore promoting the continued growth in the science, technology, and people to achieve a reliable manufacture of high-quality, low-cost pharmaceutical products.