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

这个小型企业创新研究(SBIR)第二阶段项目旨在开发一个新的按设计质量(QBD)软件平台，以满足FDA的QBD倡议的需求，这是一个创新药物开发、制造和质量保证的框架。QBD在四个层面上实施：过程理解；设计质量；监控、预测和控制；以及持续改进。由于缺乏可重用和可扩展的QBD软件平台来组装执行、记录和集成QBD工作流的QBD工具，阻碍了QBD的实施。在第一阶段的项目中，我们成功地演示了QbD软件平台在第一个QbD级别的工作流程中的应用。该项目将把研究扩展到其他层面，并在三个主要方面增强QbD软件平台：1)增加QbD数据集对象的管理能力；2)扩大QbD工作流对象池；3)增加与中央存储库的协作能力。我们将通过与制药公司研究合作者共同开发的使用场景来测试、评估和验证QBD软件平台。该计划的最终目标是开发一种商业QBD软件工具包，使科学家和工程师能够实施QBD，以提高生产效率和监管灵活性。我国公民的健康取决于安全、有效和负担得起的药物的可用性。制药公司需要利用创新、尖端科学和工程知识以及质量管理的最佳原则来应对新发现(例如，复杂的药物输送系统和纳米技术)和个性化治疗或基因定制治疗的挑战。FDA和全球制药界正在为一场监管政策革命--按设计质量(Quality-by-Design，QBD)奠定基础，这一革命提供了一个框架，使监管过程能够更容易地在药物开发、生产和质量保证方面采用最先进的技术进步。QBD将重点从“通过测试获得质量”转变为“通过设计获得质量”，即在生产过程中建立质量，而不是依赖资源密集型质量控制系统来防止有缺陷的产品出厂。本建议的设计质量(QBD)软件平台使科学家和工程师能够对制造质量实施最先进的多变量分析和机器学习。此外，鉴于制造占药品成本的25%，设备利用率低于40%，批次质量不合格率在5%至15%之间，有效实施QBD将提高效率，降低药品成本，增强美国制药业的竞争力。

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.