A Practical Tool for Managing the Complexity of Biologics Process Manufacturing

管理生物制品工艺制造复杂性的实用工具

• 批准号: 8199814
• 负责人: Joseph F Pekny
• 金额: $ 15万
• 依托单位: ADVANCED PROCESS COMBINATORICS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199814
• 关键词: Address; Capital; Caring; Cell Culture Techniques; Communication; Computer software; Data; Development; Disease; Drug Industry; Due Process; Economics; Environment; Event; Funding; Generic Drugs; Genetic Engineering; Genetic screening method; Goals; Human Genome Project; Imagery; Individual; Investments; Literature; Marketing; Medicine; Metabolic; Methodology; Molecular Profiling; Online Systems; Pharmaceutical Preparations; Pharmaceutical Technology; Pharmacologic Substance; Phase; Plants; Population; Process; Production; Proteomics; Published Comment; Research; Running; Schedule; Science; Series; Small Business Innovation Research Grant; Social Network; Software Tools; System; Techniques; Therapeutic; Therapeutic Agents; Time; Uncertainty; United States National Institutes of Health; base; cost; data management; design; drug development; health care quality; improved; manufacturing process; operation; patient population; pressure; simulation; success; tool; virtual; web based interface

DESCRIPTION (provided by applicant): Advances in pharmaceutical drug development and the pioneering use of cell-cultures to produce biologic compounds have the potential to usher in a new era of medicine. There are incredible opportunities for development of drugs which are highly effective in treating disease for subsets of the greater population. However, there are a number of practical factors which make this a real challenge. The rising cost and challenge of quality health care has placed tremendous pressure on the pharmaceutical industry to drugs to market faster and with lower costs. For traditional pharmaceutical compounds the time and cost to develop a new drug is enormous. Even after a successful drug is developed there is only a short time window to recoup costs before the market is open to low-cost generic compounds. This leads to several critical problems, but one of the main issues is that these economic pressures do not allow pharmaceutical companies to economically deliver drugs for anything other than very large populations of patients. To develop therapeutic agents for small populations and start to reap the benefits of personalized medicine it is necessary to reduce the cost of biologics plants and to maximize the capacity and operational efficiency of manufacturing. We propose a Phase I NIH SBIR project to address the critical barriers of high cost, high process uncertainty and variability. This project, aimed at developing a virtual biologics plant, has the following specific aims: Aim 1 - Apply stochastic optimization techniques to provide Sim-Opt capability for our VirtECS(R) Scheduling Engine to manage process variability: research and apply stochastic optimization techniques in the literature to scheduling; ii) automate large numbers of runs for simulation plus optimization (Sim-Opt), and iii) develop the data management techniques required to analyze such data. Aim 2 - Adapt the VirtECS(R) Scheduling engine for rapid 'Wet-start' rescheduling of processes due to the inherent uncertainty of biologics processes and the need to constantly adapt to changing conditions: i) adapt the solver to handle in-process tasks; ii) handle initial intermediate storage conditions; and iii) develop a methodology to restart the scheduler when unanticipated events occur. Aim 3 - Develop a tool to help with visualization of results and communication about operations in the dynamic environment of a biologics manufacturing plant: i) visualize schedules information via a web-based interface; ii) allow individual users to control what information they see, and iii) provide a web-based capability for users to comment on scheduled activities and communicate with each other. PUBLIC HEALTH RELEVANCE: The ultimate goal of this project is to develop a software package and a set of tools and processes to optimize the scheduling of biologics plants which make advanced medicines. This package will provide powerful capabilities for designing and operating pharmaceutical facilities in a way that reduces cost for the consumer and which may allow the era of personalized medicine to take a great step forward. The aim of this Phase I project is to investigate the technical and financial feasibility of such a system, based on the VirtECS(R) Scheduling Engine.

描述（由申请人提供）：药物开发的进步和细胞培养生产生物化合物的开创性使用有可能迎来医学的新时代。有难以置信的机会来开发药物，这些药物在治疗更大人群的亚群疾病方面非常有效。然而，有许多实际因素使这成为一个真正的挑战。不断上升的成本和高质量医疗保健的挑战给制药业带来了巨大的压力，迫使它们以更快的速度和更低的成本将药品推向市场。对于传统的药物化合物来说，开发一种新药的时间和成本是巨大的。即使在成功开发出一种药物之后，在市场向低成本仿制药开放之前，也只有很短的时间窗口来收回成本。这导致了几个关键问题，但其中一个主要问题是，这些经济压力不允许制药公司以经济的方式为大量患者提供药物。为了开发针对少数人群的治疗药物并开始获得个性化医疗的好处，有必要降低生物制剂工厂的成本，并最大限度地提高生产能力和运营效率。我们提出了一项I期NIH SBIR项目，以解决高成本，高工艺不确定性和可变性的关键障碍。该项目旨在开发虚拟生物制剂工厂，具体目标如下：目标1 -应用随机优化技术为我们的VirtECS(R)调度引擎提供simm - opt功能，以管理过程可变性；研究并应用文献中的随机优化技术进行调度；ii)自动运行大量模拟和优化（Sim-Opt），以及iii)开发分析此类数据所需的数据管理技术。目标2 -调整VirtECS(R)调度引擎，以实现由于生物制品过程固有的不确定性和不断适应不断变化的条件而对进程进行快速“湿启动”重新调度：i)调整求解器以处理进程内任务；Ii)处理初始中间存储条件；iii)开发一种在意外事件发生时重新启动调度器的方法。目标3 -开发一种工具，以帮助在生物制剂制造工厂的动态环境中可视化结果和沟通操作：i)通过基于web的界面可视化时间表信息；Ii)允许个人用户控制他们看到的信息，以及iii)为用户提供基于web的功能，以便对预定的活动进行评论并相互通信。