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

该COVID-19 RAPID研究计划将为药物活性成分羟氯喹（HCQ）的生产要求和国内生产能力绘制数字地图。HCQ可能为COVID-19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，这可能导致美国的HCQ和其他重要药物短缺。药品短缺的部分原因是国内药品供应链变得更长、更复杂和更分散。美国拥有先进的化学品和药品制造能力，但许多关键原材料和/或中间体是在世界其他地方制造的。不太复杂的市场可以通过增加产量来应对短缺，但物流方面的挑战--特别是供应链的复杂性--限制了国内制药商轻松增加产量的能力。虽然美国在全球化学品出口中排名第二，但由于没有明确的生产要求或能够满足这些要求的国内制造能力，美国的大部分制造能力无法随时利用来解决预期的短缺问题。HCQ将作为一个案例进行“映射”，有可能更快地改进和应用相同的方法学，以更快地应用于对公众有价值的其他化合物，用于治疗COVID-19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-更具体地说，一个知识图-在羟氯喹（HCQ）中的活性药物成分（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（也被提议作为潜在的COVID-19疗法）。该项目将与宝洁公司合作，利用权威系统知识（ASK）化学系统方法，以及来自“M-Print”开放知识网络第一阶段融合加速器项目（1937017）的数据和资源。ASK方法目前被工业和政府组织用于管理机电系统制造和其他过程，但诸如此类的工具尚未在化学工业中广泛使用。项目小组假设，可以在美国和国外确定必要的源材料和中间体的供应商，更重要的是，如果这是确保稳定供应的理想结果，则可以在美国设施内重新调整HCQ工艺所需的化学转换。为了验证美国HCQ制造可以优化以最大限度地减少全球供应链挑战的特定假设，该团队将开发一种使用美国可用原材料的模型方法，包括将这些原材料转化为HCQ的生产要求。对供应和制造模式的更深入的了解可以帮助供应链内外的决策者优化流程。总体目标是快速满足API制造的关键需求，并在危机时期重新构想其优化。该RAPID奖由整合活动办公室的融合加速器计划使用冠状病毒援助，救济和经济安全（CARES）法案的资金颁发，并与融合加速器轨道A相关：开放知识网络。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。

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.