RAPID: Enhancing US manufacturing of small molecule active pharmaceutical ingredients (APIs) using Authoritative Systems Knowledge (ASK) - (ASK4APIs)

这一新冠肺炎快速研究计划将为药物活性成分羟基氯喹(HCQ)开发一张生产需求和国内制造能力的数字地图。HCQ可能为新冠肺炎提供一种治疗选择；然而，大流行似乎已经扰乱了全球药品供应，这可能导致该药物和其他重要药物在美国短缺。药品短缺的部分原因是国内药品供应链变得更长、更复杂和支离破碎。美国拥有尖端的化学品和制药制造能力，但许多关键原材料和/或中间体是在世界其他地方生产的。不那么复杂的市场可以通过增加产量来应对短缺，但物流挑战--尤其是供应链的复杂性--限制了国内制药商轻松提高产量的能力。尽管美国在全球化学品出口中排名第二，但其大部分制造能力无法轻易利用来弥补预期的短缺，因为没有能够满足这些要求的生产需求或国内制造能力的清晰地图。HCQ将作为一个例子被“绘制成地图”，有可能更快地将相同的方法改进和应用于其他对公众有价值的化合物，用于治疗新冠肺炎或应用于其他疾病或紧急挑战。该项目团队将开发一个系统的本体论--更具体地说，是一个知识图谱--关于羟基环喹(HCQ)中活性药物成分(API)的HCQ生产。该项目计划从HCQ开始，但该方法应该很容易适用于其他分子，如Remdesivir或Favipiravir(这两种药物也被建议作为潜在的新冠肺炎疗法)。该项目将与宝洁公司合作，利用权威的系统知识(ASK)化学系统方法，以及来自“M-Print”开放式知识网络第一阶段融合加速器项目(1937017)的数据和资源。目前，工业和政府组织使用ASK方法来管理机电系统制造和其他流程，但此类工具在化学工业中尚未广泛使用。该项目团队假设，可以在美国和海外找到必要的原材料和中间体的供应商，更重要的是，如果这是确保强劲供应的理想结果，那么可以在美国设施内重新装备HCQ工艺所需的化学转化。为了测试特定的假设，即可以优化美国的HCQ制造以最大限度地减少全球供应链挑战，该团队将开发一个使用美国可获得的原材料的模型方法，包括将这些原材料转化为HCQ的生产要求。对供应和制造模式有更深入的了解，以帮助供应链内外的决策者优化流程。总体目标是迅速满足原料药制造中的关键需求，并在危机时刻重新设想其优化。这一快速奖项由综合活动办公室的融合加速器计划利用冠状病毒援助、救济和经济安全(CARE)法案的资金颁发，并与融合加速器轨道A：开放知识网络相关。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This COVID-19 RAPID research program will develop a digital map of production requirements and domestic manufacturing capacity for the pharmaceutical active ingredient, hydroxychloroquine (HCQ). HCQ may provide a treatment option for COVID-19; however, the pandemic already appears to be disrupting the global pharmaceutical supply, which may cause shortages of this and other important medicines in the United States. Shortages of medicines occur in part because the domestic drug supply chain has become longer, more complex, and fragmented. The United States has sophisticated chemicals and pharmaceutical manufacturing capability, but many key raw materials and/or intermediates are manufactured elsewhere in the world. Less complicated markets could respond to a shortage by increasing production, but logistical challenges – especially the complexity of the supply chain – limit the ability of domestic drug manufacturers to easily increase production. Although the United States ranks second in global chemicals exports, much of its manufacturing capacity is unable to be readily leveraged to address anticipated shortfalls because there is no clear map of production requirements or domestic manufacturing capacity that is capable of meeting these requirements. HCQ will be “mapped” as an example case, with the potential to refine and apply the same methodology even more rapidly to other compounds of value to the public in treating COVID-19 or for application to other diseases or emergent challenges. The project team will develop a systematic ontology - and more specifically, a knowledge graph – of HCQ production of the active pharmaceutical ingredient (API) in hydroxycloroquine (HCQ). The project plans to start with HCQ, but the methodology should be readily applicable to other molecules such as Remdesivir or Favipiravir (which have also been proposed as potential COVID-19 therapies). In partnership with Procter & Gamble, the project will leverage an Authoritative System Knowledge (ASK) chemical systems approach, as well as data and resources from the “M-Print” open knowledge network Phase I Convergence Accelerator project (1937017). The ASK methodology is currently used by industry and government organizations to manage electromechanical systems manufacturing and other processes, but tools such as these are not yet widely used in the chemicals industry. The project team hypothesizes that suppliers of necessary source materials and intermediates in the US and abroad can be identified, and more importantly that the chemical transformations required for the HCQ process could be retooled within American facilities if that were a desirable outcome to ensure robust supply. To test the specific hypothesis that US manufacturing of HCQ could be optimized to minimize global supply chain challenges, the team will develop a model approach that uses raw materials available in the U.S., including the production requirements to transform these raw materials into HCQ. The greater insights into supply and manufacturing patterns are envisioned to help decision-makers both inside and outside the supply chain optimize processes. The overall goal is to rapidly address a critical need in API manufacturing and reimagine its optimization in times of crisis.This RAPID award is made by the Convergence Accelerator program in the Office of Integrative Activities using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act, and is associated with the Convergence Accelerator Track A: Open Knowledge Network.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.