A Practical Tool for Managing the Complexity of Biologics Process Manufacturing

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开启医学的新纪元。有令人难以置信的机会发展药物，这些药物在治疗更大人口的部分人群中的疾病方面非常有效。然而，有许多实际因素使这成为一个真正的挑战。不断上涨的成本和优质医疗保健的挑战给制药业带来了巨大的压力，要求药品以更快的速度和更低的成本进入市场。对于传统药物化合物来说，开发一种新药的时间和成本都是巨大的。即使在一种成功的药物被开发出来之后，在市场对低成本的仿制药开放之前，收回成本的时间窗口也很短。这导致了几个关键问题，但主要问题之一是，这些经济压力不允许制药公司为非常大的患者群体以外的任何人提供经济上的药物。为了开发适用于较小人口的治疗剂，并开始获得个性化药物的好处，必须降低生物制剂厂的成本，并最大限度地提高生产的能力和运作效率。我们提出了NIH SBIR第一阶段项目，以解决高成本、高工艺不确定性和可变性的关键障碍。该项目旨在开发一个虚拟生物制药厂，有以下具体目标：目标1-应用随机优化技术，为我们的VirtECS(R)调度引擎提供SIM-OPT功能，以管理过程的可变性：研究并将文献中的随机优化技术应用于调度；ii)使大量模拟和优化运行自动化(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-使VirtECS(R)调度引擎适用于对工艺的快速“湿启动”重新调度，这是由于生物制药工艺固有的不确定性和不断适应不断变化的条件的需要：i)使求解器适应处理进程中的任务；ii)处理初始中间存储条件；以及iii)开发一种方法，以便在意外事件发生时重新启动调度器。目标3-开发一种工具，以帮助可视化结果和关于生物制剂制造厂动态环境中的操作的沟通：i)通过基于网络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)为用户提供基于网络的能力，以评论所安排的活动并相互交流。 与公共卫生相关：该项目的最终目标是开发一个软件包和一套工具和流程，以优化生产先进药物的生物制药厂的调度。这一套餐将为设计和运营制药设施提供强大的能力，以降低消费者的成本，并可能使个性化药物时代向前迈进一大步。这个第一阶段项目的目的是调查这样一个基于VirtECS(R)调度引擎的系统的技术和财务可行性。

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.