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

Office of the Director - 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.