(541d) Keynote Talk: Integrated Quality By Design in (Bio)Pharmaceutical Manufacturing

This presentation describes a Quality-by-Design approach for an accelerated process development workflow for the design of integrated (bio)pharmaceutical manufacturing systems from drug substance to drug product. This approach draws R&D and management into closer alignment and execution while defining product critical quality attributes, the operational design space, the manufacturing process, and the control strategy by integrated use of the ICH quality quartet – namely Q8(R2), Q9, Q10, and Q11. The workflow employs process intensification, micro-scale technologies, modular unit operations with integrated process control and monitoring systems, systems integration, and full plant automation. The presentation describes how to best develop and transfer knowledge between steps in the workflow via mechanistic models, data analytics, and machine learning. The approach is illustrated in more than a half dozen small- and large-molecule applications, including where process equipment was first designed digitally using first-principles models, then constructed and implemented experimentally, with the experimental results confirming model predictions. These applications include a wide variety of upstream, downstream, and formulation unit operations for small-molecule and biological drug manufacturing, as well as the design and operation of fully automated end-to-end manufacturing systems.