SBIR Phase I: PAT Software Platform for Process Analytical Technology Implementation

这一小型企业创新研究第一阶段研究项目旨在针对FDA的过程分析技术(PAT)计划的需求，建立一个新型软件平台的“概念验证”，这是一个创新药物开发、制造和质量保证的框架。PAT在三个层面上实施：过程理解；设计质量；以及监控、预测和控制。由于缺乏可重复使用和可扩展的PAT软件平台，PAT的实施受到阻碍，该平台可用于构建可与越来越多的商业分析器集成和互操作的PAT分析工具。第一阶段计划旨在通过对PAT 1级工作流程的应用，为PAT软件平台进行“概念验证”，以开发过程理解。该项目将使用原型PAT软件开发工具包(PSDK)来组装用于自动执行PAT级别1工作流程的应用程序。将通过论证平台的准确性、识别、预测、性能和能力来确定可行性。第二阶段将扩展研究，以满足PAT级别2和3的要求。最终目标是提供一个商业PAT软件开发工具包，允许客户组装他们自己的PAT应用程序，供研究、开发和工厂工人使用，以提高制造质量。拟议的PAT软件平台直接支持FDA的过程分析技术(PAT)倡议，该倡议是该机构21世纪cGMP的一部分，旨在帮助全球制药界达到由以下组成的“期望状态”：(1)通过设计有效和高效的制造工艺来实现并确保产品质量和性能；(2)产品规格建立在对配方和工艺因素如何影响产品性能的机械理解的基础上；(3)制造商能够实现持续改进和持续的“实时”质量保证。PAT软件平台允许组装集成的和可互操作的PAT软件应用程序，这些应用程序(A)提供用于分析、监测、控制和预测(建模)的公共环境，(B)促进软件、分析器和存储系统之间的PAT数据交换，以及(C)提供单一环境，在其中挖掘和分析数据以提取过程知识。PAT软件平台将帮助制药公司降低验证和培训成本，最大限度地减少部署时间，并提高PAT系统的可靠性。一个通用的PAT软件平台还将通过减少对定制接口代码的需求来帮助加快PAT被制药业接受，因为定制接口代码的生产和维护既昂贵又耗时。

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.