T. Li
U.S. Pharmacopeia,
United States
Keywords: Continuous Biomanufacturing
Summary:
The United States Pharmacopeia (USP) Advanced Manufacturing Technologies – Biologics Program is committed to accelerating the biopharmaceutical industry’s transition to continuous biomanufacturing through application-driven initiatives with strong industry relevance. The program focuses on three critical pillars: workforce development, real-time process monitoring and control, and integrated equipment platforms. USP is developing comprehensive training modules that combine theoretical knowledge with hands-on learning, concentrating on key unit operations in continuous biomanufacturing. These include perfusion bioreactors, continuous chromatography, and inline buffer conditioning systems. The goal is to close existing knowledge gaps, streamline operational and regulatory complexities, and prepare the workforce to manage fully integrated, end-to-end continuous manufacturing environments. In the area of process monitoring, USP is actively identifying and evaluating advanced, label-free sensors and probes—such as Raman and near-infrared (NIR) spectroscopy, online UV absorbance detectors, and biocapacitance probes—alongside emerging real-time analytical tools. These technologies enable real-time measurement of critical quality attributes (CQAs) and critical process parameters (CPPs), in alignment with the FDA’s Process Analytical Technology (PAT) framework and ICH Q8–Q10 guidelines. These capabilities also support the implementation of Real-Time Release Testing (RTRT) and the principles of Quality by Design (QbD). Complementary efforts in model-based control strategies and soft sensor development aim to enable adaptive, predictive control, supporting digital integration and ensuring robust performance in continuous bioprocessing. To support seamless end-to-end biomanufacturing, USP is assessing modular and scalable equipment platforms across upstream and downstream operations. These include intensified perfusion culture systems, multi-column continuous chromatography, and integrated purification trains designed to maintain steady-state conditions, minimize hold steps, reduce contamination risks, and enhance operational efficiency. Recognizing the foundational importance of starting materials, USP is also expanding its focus to the characterization and control of raw materials in continuous biomanufacturing, where consistency, traceability, and quality are critical to maintaining process stability and ensuring product integrity. Through strategic collaborations with industry, academia, and technology developers, USP is advancing regulatory science, supporting the standardization of PAT tools, and facilitating broader adoption of platform technologies. We will share findings from recent technology evaluations, highlight progress in workforce training and platform integration, and identify opportunities for collaboration to address outstanding challenges and drive the industry-wide adoption of continuous biomanufacturing.