SBIR Phase II: Software Platform for Quality-by-Design Implementation

This Small Business Innovation Research (SBIR) Phase II project aims to develop a novel Quality-by-Design (QbD) software platform directed at the needs of FDA's QbD initiative, a framework for innovative pharmaceutical development, manufacturing and quality assurance. QbD is implemented at four levels: process understanding; quality by design; monitor, predict and control; and continuous improvement. QbD implementation is hampered by the lack of a reusable and extensible QbD Software Platform for assembling QbD tools that execute, document and integrate QbD workflow. In the Phase I program, we successfully demonstrated 'proof-ofconcept' for the QbD Software Platform for application to the first QbD level workflow. This project will extend research to the other levels and enhance the QbD Software Platform in three principal ways: 1) increase capabilities for managing QbD data-set objects; 2) enlarge the pool of QbD workflow objects; and 3) add collaboration capability in conjunction with a centralized repository. We will test, evaluate and validate the QbD Software Platform through use scenarios developed in conjunction with pharmaceutical-company research collaborators. The ultimate goal of the program is to develop a commercial QbD software toolkit that enables scientists and engineers to implement QbD for increased manufacturing efficiency with regulatory flexibility. The health of our nation's citizens depends on the availability of safe, effective and affordable medicines. Pharmaceutical companies need to employ innovation, cutting-edge scientific and engineering knowledge, and the best principles of quality management to respond to the challenges of new discoveries (e.g., complex drug delivery systems and nanotechnology) and individualized therapies or genetically tailored treatments. The FDA and global pharmaceutical community are laying the foundation for a regulatory policy revolution, Quality-by-Design (QbD), that provides a framework for allowing regulatory processes to more readily-adopt state-of-the-art technological advances in drug development, production and quality assurance. QbD shifts focus from 'quality by testing' to 'quality by design', i.e. build quality into the process rather than rely on resource-intensive quality control systems to prevent defective products from leaving the factory. The Quality-by-Design (QbD) Software Platform of the present proposal enables scientists and engineers to implement state-of-the-art multi-variate analysis and machine learning to manufacturing quality. Additionally, given that manufacturing represents 25% of drug cost, equipment utilization is below 40%, and batch quality failures range from 5 to 15%, the effective implementation of QbD will enable improved efficiency providing lower drug costs and increased competitiveness for the US pharmaceutical industry.