SBIR Phase II: Novel pharmaceutical manufacturing technologies to deliver more affordable medications to patients faster and with better quality

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是使一种革命性的药品制造工艺成为可能。该项目包括新工艺技术的开发，以及将这些工艺集成到端到端的连续生产线中，可以连续生产药物（24/7基础）。这与目前在离散时间点生产大量药品的方法不同（例如，每年生产几次大批量药品）。该工艺的试验工厂显示出显著的操作优势，上市药品生产时间从200天减少到2天，工厂占地面积减少了90%，预计成本降低了50%，同时提高了产品质量。对社会的影响将是巨大的：患者将获得更优质的药物；药品短缺将大大减少；制药公司将能够以更具成本效益和效率的方式生产和分销药品，使它们能够将更多资金重新分配给研发（开发新药）。最后，有可能将制造工厂和工作岗位迁回美国（更高效的流程=更低的成本）。拟议的项目建立在成功的第一阶段SBIR项目的基础上，以及一家主要研究机构和一家领先制药公司之间的五年合作，旨在开发一种新的连续生产工艺，以克服当前标准批量生产的局限性。这个NSF项目的第一个目标是进一步开发多步骤连续制造过程的两个新元素（即固体剂型的非均质结晶和静电纺丝），以便它们在不同的操作条件下可靠地运行。这一点很重要，因为商业生产需要它们连续、可靠地24/7运行。因此，这些新的装置操作将在不同的操作条件和起始材料下进行研究，同时对其设计进行优化。当单元操作达到以下目标时，将定义成功：1)最大的操作效率，2)行业标准制造能力，以及3)在研发制造范围内使用的资格。第二个目标是将这两个单元整合到一个更广泛的端到端连续制造过程中，能够连续生产高质量的药品。综合工艺还将包括分离、过滤和干燥三个单元操作，这些操作是在SBIR项目的第一阶段开发的。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to enable the availability of a revolutionary manufacturing process for pharmaceuticals. The project consists of the development of novel process technologies, as well as the integration of these processes into an end-to-end continuous manufacturing line that can produce drugs continuously (24/7 basis). This is different from the current methodology that produces large quantities of drugs at discrete time points (e.g. large batch quantities are produced several times a year). A working pilot plant of this process demonstrated significant operational advantages with a marketed drug-production time was reduced from 200 days to 2 days, plant footprint decreased by 90%, projected costs reduced by 50%, while improving product quality. The impact on society will be considerable: patients will receive better quality drugs; drug shortages will be greatly reduced; and pharmaceutical companies will be able to manufacture and distribute their drugs in a much more cost-effective and efficient manner, allowing them to reallocate more capital to Research and Development (new drugs developed). Finally, it will be possible to relocate manufacturing plants and jobs back in the U.S. (more efficient processes = lower costs).The proposed project builds upon a successful Phase I SBIR project, as well as five years of collaboration between a premier research institution and a leading pharmaceutical company aimed at developing a novel continuous manufacturing process to overcome the limitations of the current standard, batch manufacturing. The first objective of this NSF project is to further develop two novel elements of a multistep, continuous manufacturing process (i.e. heterogeneous crystallization and electrospinning for solid dosage forms), so they run reliably under different operating conditions. This is important because commercial production requires that they perform consistently and reliably 24/7. Thus, these novel unit operations will be studied under different operating conditions and starting materials, while their design is optimized. Success will be defined when the unit operations achieve: 1) maximal operational efficiency, 2) industry standard manufacturing capabilities, and 3) qualification to be used across the Research and Development manufacturing spectrum. The second objective is to integrate these two units into a broader end-to-end continuous manufacturing process capable of producing high-quality pharmaceuticals on a continuous basis. The integrated process will also feature three unit operations on separation, filtration and drying that were developed during Phase I of this SBIR project.