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

I-Corps：小型化端到端药品制造平台

• 批准号: 1745798
• 负责人: Zoltan Nagy
• 金额: $ 5万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1745798&HistoricalAwards=false
• 关键词: Corps; Miniaturized; End; Pharmaceutical; Manufacturing

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 Moreover, the outdated infrastructure has weaknesses in terms of product yield and environmental impact.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

这个I-Corps项目的更广泛/商业影响是一个微型，按需药物制造平台，可扩展且有效地部署，高度自动化且在产品发布时快速。该项目的目的是减少制造和库存成本，进而克服药物短缺。从广义上讲，当前的全球制药行业易于供应链中断，药物短缺和药品价格上涨。一个主要的促成因素是遗留工厂和过程，这些工厂和过程仅限于间歇性和缓慢的产量。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。考虑到满足对临床试验供应需求，对批准的不确定性以及其他资源限制的压力，药物开发活动通常只是一系列的过程规模，更少强调对下一代制造过程的创新，从长远来看，这在所有方面都可以更好。因此，该项目是朝着更灵活，更经济，更绿色且最终更可持续的药物制造基础设施的重大推动。本I-Corps项目探讨了基于微流体的，连续流的药物制造设备的商业潜力。它代表了从常规，劳动密集型，批处理药物制造过程的范式转变。微流体（MFDS）是制造的微通道，其比常规批处理反应器小的一千倍。反过来，MFD的表面积与体积比的增加一千倍，从而使热量和大传质以及其他优势非常快。由于该过程是连续的，因此可以将系统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，不仅可以通过过程设计，还可以通过高级过程控制来确保产品质量。从综合和纯化的角度来看，MFD可以精确处理以前无法访问但高效，加压且经常进行放热途径的处理。这会导致更加绿色，更安全的过程，其吞吐量更高，浪费较少。在配方方面，MFD提供均匀的结晶环境，从而导致单分散晶体尺寸分布，从而在关键产品质量（例如形状和尺寸）方面具有出色的可重复性。