Planning Grant: Engineering Research Center for Continuous Membrane-enabled Manufacturing of Pharmaceutical (CMMP)

规划资助：连续膜制药工程研究中心（CMMP）

• 批准号: 1937021
• 负责人: Kamalesh Sirkar
• 金额: $ 9.44万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1937021&HistoricalAwards=false
• 关键词: Planning; Grant; Engineering; Research; Center

The Planning Grants for Engineering Research Centers competition was run as a pilot solicitation within the ERC program. Planning grants are not required as part of the full ERC competition, but intended to build capacity among teams to plan for convergent, center-scale engineering research.Development of continuous membrane-enabled manufacturing of pharmaceuticals will open hitherto nonexistent opportunities for both conventional and reactive separations in the chemical, fine chemicals and petrochemical industries. Membrane technologies are compact, modular, easily scalable, highly energy efficient and are capable of extraordinary separations in a continuous fashion. Membrane reactors can achieve a synthesis level not achievable by conventional tubular reactors and are now well-established as a process intensification tool. To overcome many deficiencies of batch manufacturing, we propose an ERC for Continuous Membrane-Enabled Manufacturing of Pharmaceuticals (CMMP) using membrane technologies. The proposed ERC has three goals: (1) Develop, adapt and transition new membranes, novel membrane technologies and membrane reaction-separation concepts developed by the CMMP team and others into individual steps of continuous manufacturing of active pharmaceutical ingredients (APIs) in the molecular weight range of about 150-1000 Da; (2)Integrate the individual membrane-based steps into a multistep API production process and demonstrate the feasibility of a primarily membrane-based continuous process equipped with process analytical technology (PAT) to synthesize APIs economically with high efficiency, quality, and safety;(3) Develop an educational program and foster an environment that transforms education relevant to pharmaceutical production as well as influences fine chemicals manufacturing processes with the program-developed innovations. In this Planning Grant, academic stakeholders from six universities will work with stakeholders from major pharmaceutical companies, contract manufacturing organizations, membrane manufacturers, and process system developers to identify key pharmaceutical systems with synthesis-cum-separation steps ready for introduction of new membrane technologies. During this grant, stakeholders will deliberate on potential membrane-based demonstration systems for multistep synthesis of select APIs. These systems will form the basis of the ERC pre-proposal. A stakeholder community will be formed to guide progress of CMMP and creation of a strong academic program to assist high school, undergraduate and graduate students learn the paradigm change when transitioning from batch production into continuous membrane-based API manufacturing. Membrane technologies have very limited footprint in pharmaceutical manufacturing due to perceived concerns regarding reduced solvent resistance and limited selectivities in organic solvent-based systems. New dense membranes are emerging with very high solvent resistance (HSR) and exquisite selectivities that can separate mixtures of smaller molecules and organic solvents via processes such as, organic solvent reverse osmosis, organic solvent nanofiltration and membrane pervaporation. Their further development will usher in a new era of membranes with extraordinary performance and understanding of how to design them. Microporous HSR membranes can be used for nondispersive solvent extraction, gas-liquid membrane contactors and reactors for hydrogenation, dehydrogenation, ozonation, membrane mixing, crystallization and adsorption. Dense, nanoporous membranes may be used in membrane reactors to achieve high selectivity and yield. Introduction of such membranes operating continuously into each step of the API synthesis train will radically transform pharmaceutical production introducing high efficiencies with compact/scalable membrane modules. This grant will allow stakeholders to identify membrane processes for API production that substantially enhance performances of reaction and separation steps. This grant will also guide an ERC pre-proposal in selecting API synthesis examples having a train of continuously operated membrane-based reaction and separation steps thereby demonstrating the capability of membrane devices to operate with high efficiency and reduced cost.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.

工程研究中心规划补助金竞赛是作为 ERC 计划内的试点征集活动进行的。作为整个 ERC 竞赛的一部分，规划拨款不是必需的，而是旨在培养团队之间的能力，以规划融合的、中心规模的工程研究。连续膜技术药物制造的发展将为传统和反应性技术提供迄今为止不存在的机会化学、精细化学品和石化工业中的分离。膜技术结构紧凑、模块化、易于扩展、能源效率高，并且能够以连续方式进行非凡的分离。膜反应器可以达到传统管式反应器无法达到的合成水平，并且现已成为一种成熟的工艺强化工具。为了克服批量生产的许多缺陷，我们提出了使用膜技术进行连续膜药物制造 (CMMP) 的 ERC。拟议的 ERC 具有三个目标：(1) 开发、调整和过渡由 CMMP 团队和其他人开发的新膜、新颖膜技术和膜反应分离概念，以在分子中连续生产活性药物成分 (API) 的各个步骤。重量范围约150-1000 Da； (2)将各个基于膜的步骤集成到多步API生产工艺中，并证明配备过程分析技术（PAT）的主要基于膜的连续工艺的可行性，以经济、高效、优质和安全地合成API；（ 3) 制定教育计划并营造一个环境，改变与药品生产相关的教育，并通过计划开发的创新影响精细化学品的制造工艺。在这项规划拨款中，来自六所大学的学术利益相关者将与来自主要制药公司、合同制造组织、膜制造商和工艺系统开发商的利益相关者合作，确定具有合成和分离步骤的关键制药系统，为引入新的膜技术做好准备。在这笔资助期间，利益相关者将审议潜在的基于膜的演示系统，用于选定 API 的多步合成。这些系统将构成 ERC 预提案的基础。将成立一个利益相关者社区来指导 CMMP 的进展并创建强大的学术计划，以帮助高中生、本科生和研究生了解从批量生产过渡到基于膜的连续 API 制造时的范式变化。由于人们担心有机溶剂型系统的耐溶剂性降低和选择性有限，膜技术在药品制造中的应用非常有限。新型致密膜正在出现，具有非常高的耐溶剂性（HSR）和精致的选择性，可以通过有机溶剂反渗透、有机溶剂纳滤和膜渗透蒸发等工艺分离较小分子和有机溶剂的混合物。它们的进一步发展将开创具有非凡性能和对如何设计它们的理解的膜的新时代。微孔HSR膜可用于非分散溶剂萃取、气液膜接触器和加氢、脱氢、臭氧化、膜混合、结晶和吸附反应器。致密的纳米多孔膜可用于膜反应器中以实现高选择性和产率。将这种连续运行的膜引入 API 合成系列的每个步骤将从根本上改变制药生产，通过紧凑/可扩展的膜模块实现高效率。这笔赠款将使利益相关者能够确定用于 API 生产的膜工艺，从而大大提高反应和分离步骤的性能。这笔赠款还将指导 ERC 预提案选择 API 合成示例，这些示例具有一系列连续运行的基于膜的反应和分离步骤，从而证明膜装置高效运行和降低成本的能力。该奖项反映了 NSF 的法定使命通过使用基金会的智力优点和更广泛的影响审查标准进行评估，并被认为值得支持。