Industry 4.0 Implementation in Continuous Pharmaceutical Manufacturing

项目概要/摘要。 在过去的十年中，我们的结构化有机颗粒系统中心（C-SOPS）团队领导了 开发实验和计算基础设施，以实现设计质量（QbD） 为了持续的药品生产，与食品和药物管理局密切合作， (FDA)和工业。展望未来，制造业的未来是工业4.0范式， 在当前的制造业趋势（工业3.0 -自动化和信息化的数字时代）下， 在整个制造供应链中实现更自主和分散的决策。的 朝着这个方向发展的好处是巨大的，工业界已经认识到它们对改善环境的影响。 可靠性、安全性、质量和安全性。 这项提案是罗格斯大学领导的一项广泛倡议的概念组成部分， 持续制造的卓越中心，利用现有的优势和以前的工作， 在罗格斯大学和普渡大学的成功，开发下一代制药连续生产 (CM)符合工业4.0未来标准。具体目标是： 具体目标1：设计和实施综合数据管理和信息学基础设施， 下一代连续制药工艺。 具体目标2：开发利用信息系统的工艺知识提取策略 在目标1下建立，用于智能过程监控、故障诊断、材料跟踪和真实的时间风险 考核 具体目标3：使用 目标1的信息学基础结构和目标2的知识提取策略。 这项工作的结果将是一个独特的工具集所必需的（i）实施工业4.0在制药 （2）使FDA能够有效地监管此类应用。集成的基础设施， 过程和产品信息学（如罗格斯大学和普渡大学CM中试工厂所示）是 全面实施药品连续生产方法。我们设想， 从这一奋进中产生的知识、产品和培训，将提供一个实际的概念验证 以及实现蓝图，以追求其他更复杂的应用程序，包括连续API 制造和连续制造生物分子。这项工作中转让的技术将 提高CM生产线的性能，从而加速和扩大其商业化。一旦 可用，在拟议的工作中开发的工具集也应该被监管机构广泛使用， 应用范围广泛，包括批量生产、边缘和可疑产品及工艺分析 （无论是不合标准的、受污染的、掺假的还是伪造的），以及药物以外的应用。

Project Summary/Abstract. In the last decade, our Center for Structured Organic Particulate Systems (C-SOPS) team has led the development of the experimental and computational infrastructure needed to enable Quality by Design (QbD) for continuous pharmaceutical manufacturing, working very closely both with the Food and Drug Administration (FDA) and with industry. Moving forward, the future of manufacturing is the industry 4.0 paradigm, which builds upon the current manufacturing trend (industry 3.0 – digital age of automation and information) to move towards more autonomous and de-centralized decisions across the entire manufacturing supply chain. The benefits in moving in this direction are significant and industries have recognized their impact in improving reliability, security, quality and safety. This proposal, which is a conceptual component of a broad initiative led by Rutgers to establish a center of excellence in Continuous Manufacturing, leverages the existing strengths and previous work and successes at Rutgers and Purdue, to develop the next generation pharmaceutical continuous manufacturing (CM) processes in accordance with the Industry 4.0 future standard. The specific aims are: Specific Aim 1: Design and implementation of integrated data management and informatics infrastructure for next generation continuous pharmaceutical processing. Specific Aim 2: Development of process knowledge extraction strategies which utilize the informatics systems established under Aim 1 for intelligent process monitoring, fault diagnosis, material tracking and real time risk assessment. Specific Aim 3: Development and assessment of continuous process improvement strategies using the informatics infrastructure of Aim 1 and knowledge extraction strategies of Aim 2.! The result of this work will be a unique toolset necessary to (i) implement Industry 4.0 in the pharmaceutical industry, and to (ii) enable FDA to regulate such applications effectively. The integrated infrastructure for process and product informatics (as demonstrated in Rutgers and Purdue CM pilot-plants) is a critical part of the full implementation of continuous manufacturing methods for pharmaceuticals. We envision that the knowledge, products, and training emanating from this endeavor, will provide both a practical proof of concept and an implementation blueprint to pursue other, more complex applications including continuous API manufacturing, and continuous manufacturing of biomolecules. The technology transferred in this work will enable enhanced performance of the CM line thus accelerating and broadening its commercialization. Once available, the toolset developed in the proposed work should also be used by regulatory agencies for a wide range of applications, including batch manufacturing, analysis of marginal and suspect products and processes (whether substandard, contaminated, adulterated, or counterfeit), and also applications beyond drugs.