SBIR Phase I: Continuous, Scalable Crystallizer for Pharmaceutical Manufacturing

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是改进在5000亿美元的药品制造市场中使用的关键步骤：活性药物成分的纯化。90%的活性药物成分都是用结晶法纯化的，然而，从商业和科学的角度来看，目前的结晶方法都有缺点。这些技术很难扩大规模，维护和制造成本高昂，并且在条件和结果上存在不一致和缺乏一致性的问题。随着这里提出的技术的开发和商业化，该团队将解决可伸缩性、成本和不一致性问题，以便：1)加快向先进生产方法（连续生产）的过渡；2)促进药品生产的回流，有助于解决美国依赖外国药品制造商的国家安全挑战；3)降低药品生产成本，最终将导致更便宜的药品，造福全体人民。该SBIR一期项目建议开发一种创新的连续结晶装置，该装置可扩展，提供充分有效的固体运动，并提供高质量的结晶产品，从而满足制药市场和技术界未满足的需求。这种新颖的设计旨在有效地解决固体（晶体）移动的问题，同时提供良好控制的流动特性，这种方法从实验室到生产都可以扩展。该技术结合了几个原始功能，提供了一种新的技术方法来解决这些运输挑战。该团队将首先演示具有塞流特性的输送浆液的能力。然后，团队将演示药物的结晶，并将其与标准批次结晶方法进行比较。一旦该技术在这些条件下表现良好，该设备将扩大规模，以便在生产规模上进行测试和使用。一旦完成，商业化设备有望克服其他技术的问题，包括运输、均匀性、一致性、可重复性和成本问题，使这种新型设备成为未来制药制造的关键角色。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to improve a key step used in the $500-billion market of pharmaceutical manufacturing: purification of active pharmaceutical ingredients. Ninety percent of all active pharmaceutical ingredients are purified using crystallization, however, current approaches to crystallization have drawbacks from both the commercial and scientific points of view. These techniques are difficult to scale up, are expensive to maintain and manufacture, and are plagued by inconsistency and lack of uniformity in conditions and results. With the development and commercialization of the technology proposed here, this team will address the scalability, cost, and inconsistency issues in order to: 1) speed up the transition to advanced manufacturing approaches (continuous manufacturing), 2) facilitate the re-shoring of drug manufacturing, contributing to addressing the national security challenge of American dependence on foreign drug manufacturers, and 3) reduce drug production costs, which will eventually lead to cheaper drugs for the benefit of the entire population. This SBIR Phase I project proposes to develop an innovative, continuous crystallization device that is scalable, provides adequate and effective movement of solids, and provides high-quality crystalline products, thus fulfilling an unmet need in the pharmaceutical market and in the technical community. The novel design aims to solve the problem of moving solids (crystals) effectively while providing well-controlled flow characteristics with an approach that is scalable from lab to production. This technology uses a combination of several original features to provide a new technological approach to address these transport challenges. This team will first provide a demonstration of the ability to transport slurries with plug flow characteristics. Then, the team will demonstrate the crystallization of a pharmaceutical, benchmarking it against standard batch crystallization methods. Once the technology has been shown to function well in these conditions, the device will be scaled up, in order to be tested and used at production scale. Once complete, the commercialized device is expected to be able to overcome problems with other technologies, including issues of transport, uniformity, consistency, reproducibility, and cost, making this novel device a key player in the future of pharmaceutical manufacturing.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.