SBIR-STTR Award

This Small Business Innovation Research Phase I research project aims to establish "proof-of-concept" of a novel Software Platform directed at needs of FDA's Process Analytical Technologies (PAT) initiative, a framework for innovative pharmaceutical development, manufacturing and quality assurance. PAT is implemented at three levels: Process Understanding; Quality by Design; and Monitor, Predict and Control. PAT implementation is hampered by the lack of a reusable and extensible PAT Software Platform, which can be used to construct PAT analysis tools that integrate and interoperate with an increasing number of commercial analyzers. The Phase I program is directed at "proof-of-concept" for the PAT Software Platform through application to PAT Level 1 workflow directed at developing process understanding. The project will use a prototype PAT Software Development Kit (PSDK) to assemble an application for automated execution of PAT Level 1 workflow. Feasibility will be established by demonstrating the accuracy, identification, prediction, performance, and capability of the platform. Phase II will extend the research to address requirements for PAT Levels 2 and 3. The ultimate aim is to provide a commercial PAT Software Development Kit that allows customers to assemble their own PAT applications for use by research, development and plant workers to improve manufacturing quality. The proposed PAT Software Platform directly supports FDA's Process Analytical Technology (PAT) initiative, part of the Agency's 21st Century cGMPs, directed at helping the global pharmaceutical community reach the "desired state" consisting of the following: (1) product quality and performance are achieved and assured by design of effective and efficient manufacturing processes; (2) product specifications are based on mechanistic understanding of how formulation and process factors impact product performance; and (3) manufacturers are able to effect continuous improvement and continuous "real-time" assurance of quality. The PAT Software Platform allows assembly of integrated and interoperable PAT software applications that (a) provide a common environment for analysis, monitoring, control and prediction (modeling), (b) facilitate the interchange of PAT data among software, analyzers and storage systems, and (c) provide a single environment in which to mine and analyze the data to extract process knowledge. The PAT Software Platform will help pharmaceutical companies reduce validation and training costs, minimize deployment time and improve the reliability of PAT systems. A common PAT Software Platform would also help accelerate PAT's acceptance by the pharmaceutical industry by reducing the need for custom interface code, which is costly and time consuming to produce and maintain

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