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

这个I-Corps项目的更广泛/商业影响是一个小型化的按需制药制造平台，该平台可扩展且部署高效，高度自动化，产品发布快速。该项目的目的是降低制造和库存成本，从而克服药物短缺。从广义上讲，当前全球医药行业容易出现供应链中断、药品短缺、药价上涨等问题。一个主要的影响因素是传统的工厂和流程，这些工厂和流程仅限于间歇性和缓慢的生产。此外，过时的基础设施在产品产量和环境影响方面存在缺陷。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，药物开发活动通常只是一系列工艺规模的扩大，而不太重视下一代制造工艺的创新，从长远来看，这在各个方面都可以从根本上得到改善。因此，该项目是一个重要的推动更灵活，经济，绿色，并最终，更可持续的药物制造基础设施。这个I-Corps项目探讨了基于微流体的，连续流动的药物制造设备的商业潜力。它代表了从传统的、劳动密集型的、批量药物制造过程的范式转变。微流体（MFD）是制造的微通道，对于相同的吞吐量，它比传统的间歇式反应器小上千倍。反过来，MFD的表面积与体积比增加了1000倍，允许极快的传热和传质以及一系列其他优势;由于该过程是连续的，该系统可以与最先进的分析传感器和基于计算机的控制器进行空间集成，从而不仅可以通过工艺设计，还可以通过先进的工艺控制来确保产品质量。从合成和纯化的角度来看，MFD允许精确处理以前无法接近的，但高效的，加压的，通常是放热的途径。这将带来更环保、更安全的工艺，同时提高产量，减少浪费。在配方方面，MFD提供了均匀的结晶环境，导致单分散的晶体尺寸分布，这导致关键产品质量（如形状和尺寸）的上级再现性。

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 Moreover, the outdated infrastructure has weaknesses in terms of product yield and environmental impact.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.