I-Corps: Miniaturized, End-to-End Pharmaceutical Manufacturing Platform

这个i-Corps项目的更广泛的商业影响是一个小型化的按需制药制造平台，它具有可扩展、高效部署、高度自动化和产品发布速度快的特点。该项目的目标是降低制造和库存成本，进而解决药品短缺问题。总的来说，当前全球制药行业容易出现供应链中断、药品短缺和药品价格上涨的情况。一个主要因素是遗留的工厂和工艺，它们仅限于断断续续和缓慢的生产。此外，过时的基础设施在产品产量和环境影响方面存在弱点。考虑到满足临床试验供应需求的压力、批准的不确定性以及其他资源限制，药物开发活动往往只是一系列工艺扩大，较少强调下一代制造工艺的创新，从长远来看，这可能从根本上更好地体现在各个方面。因此，这个项目是朝着更灵活、更经济、更绿色、最终更可持续的药品制造基础设施的重要推动。这个i-Corps项目探索了基于微流控的、连续流动的制药制造设备的商业潜力。它代表着从传统的、劳动密集型的批量药物制造过程的范式转变。微流体(MFD)是在相同的处理能力下制造的微通道，它比传统的间歇反应器小一千倍。反过来，MFD的表面积体积比增加了一千倍，允许极快的热量和质量传递以及一系列其他优势；由于过程是连续的，系统可以与最先进的分析传感器和基于计算机的控制器在空间上集成，从而不仅可以通过工艺设计确保产品质量，还可以通过先进的工艺控制来确保产品质量。从合成和提纯的角度来看，MFD允许精确处理以前无法接触到的、但高效的、加压的、通常是放热的路径。这导致了更环保、更安全的工艺，具有更高的生产能力和更少的浪费。在配方方面，MFD提供了均匀的结晶环境，导致了单分散的晶体尺寸分布，从而在形状和尺寸等关键产品质量上具有卓越的重现性。

The broader/commercial impact of this I-Corps project is a miniaturized, on-demand pharmaceutical manufacturing platform that is scalable and efficient to deploy, highly automated, and fast on product release. The project's aim is to reduce manufacturing and inventory cost and in turn overcome drug shortages. Broadly speaking, the current global pharmaceutical industry is prone to supply chain disruptions, drug shortages, and drug price hikes. One major contributing factor are legacy factories and processes which are limited to intermittent and slow production. Moreover, the outdated infrastructure has weaknesses in terms of product yield and environmental impact. Given the pressure of meeting demand for clinical trial supplies, uncertainties over approvals, and other resource constraints, drug development activities have often only been a series of process scale-ups with less emphasis on innovating on the next-gen manufacturing processes, which can be fundamentally better in all aspects in the long term. Consequently, this project is a significant push towards a more flexible, economical, greener, and, ultimately, more sustainable drug manufacturing infrastructure.This I-Corps project explores the commercial potential of a microfluidic-based, continuous-flow pharmaceutical manufacturing device. It represents a paradigm shift from conventional, labor-intensive, batch drug manufacturing processes. Microfluidics (MFDs) are fabricated microchannels which are up to a thousand times smaller than a conventional batch reactor for the same throughput. In turn, MFDs offer up to a thousand times increase in the surface area to volume ratio, allowing for extremely rapid heat and mass transfer and a suite of other advantages; Since the process is continuous, the system can be spatially integrated with state-of-the-art analytical sensors and computer-based controllers, by which the product quality can be assured not only by process design, but also by advanced process control. From a synthesis and purification perspective, MFDs allow for precise handling of previously inaccessible, but highly efficient, pressurized, and often exothermic pathways. This results in greener and safer processes with higher throughput and less waste. On the formulation side, MFDs provide homogeneous crystallization environments, leading to monodisperse crystal size distributions, which leads to superior reproducibility in key product quality such as shape and size.