Organic Solvent Vapor Mass Flow Rate Monitor for Pharmaceutical Drying Operations

描述（由申请人提供）：本阶段SBIR研发提案的目标是开发一种溶剂蒸汽质量流量监测仪器，使制药公司能够根据设计质量（QbD）原则开发和监测药物生产工艺，支持FDA QbD倡议。包括癌症治疗药物在内的药物的生产通常需要使用有机溶剂的化学加工技术。虽然水是优选的溶剂，但许多药物是使用有毒有机溶剂生产的，这些溶剂必须在最终填充/完成操作之前从产品中除去。从固体形式产物中除去溶剂通常包括相分离步骤，然后是干燥步骤，在干燥步骤期间通过施加热能除去溶剂蒸气。示例性干燥操作可包括真空干燥或流化床干燥。或者，不稳定药物产品的冷冻干燥涉及用液体产品（含有溶解的固体）填充小瓶，并使溶剂升华，产生冻干饼。在所有这些操作中，工艺开发和工艺监测将受益于工艺分析技术（PAT）工具，该工具将允许连续、实时监测溶剂质量去除率。目前，没有PAT工具提供这种重要的监测能力。在拟议的第一阶段研发计划物理科学公司。将进行实验研究，证明开发有机溶剂蒸气质量流量计的可行性。有机溶剂质量流量计的成功开发将有助于通过质量平衡测定改善工艺理解和扩大规模。这将导致改进药物制造和产品质量并降低生产成本。这将提高美国制药公司的竞争力，并最终降低药品的成本。 公共卫生相关性：拟议的研发计划的成功完成将导致开发一种定量仪器，用于监测从药品中去除有毒有机溶剂。有机溶剂质量流量计将有助于更好地理解溶剂干燥动力学，并根据质量设计原则开发高效的生产工艺。这将导致更少的不可接受的批次和更一致，更高质量的产品，这将是公众消费的安全。

DESCRIPTION (provided by applicant): The goal of this Phase I SBIR R&D proposal is to develop a solvent vapor mass flow monitoring instrument that will enable pharmaceutical companies to develop and monitor drug production processes based on Quality by Design (QbD) principles, supporting the FDA QbD initiative. The production of pharmaceuticals, including drugs for cancer treatment, often requires chemical processing techniques that use organic solvents. Although water is the preferred solvent, many pharmaceuticals are produced using toxic organic solvents that must be removed from the product prior to final fill/finish operations. Solvent removal from a solid form product typically includes a phase separation step followed by a drying step during which solvent vapor is removed through the application of thermal energy. Example drying operations may include vacuum drying or fluid bed drying. Alternatively, freeze drying of labile drug products involves filling vials with liquid product (containing dissolved solids) and sublimation of the solvent producing a lyophilized cake. In all of these operations the process development and process monitoring would benefit from a process analytical technology (PAT) tool that would allow continuous, real-time monitoring of the solvent mass removal rate. Currently, no PAT tool exists that provides this important monitoring capability. During the proposed Phase I R&D program Physical Sciences Inc. will perform experimental investigations that demonstrate the feasibility of developing an organic solvent vapor mass flow meter. The successful development of an organic solvent mass flow meter will enable improved process understanding and scale-up through mass balance determinations. This will lead to improved drug manufacturing and product quality and reduced production costs. This will improve the competitiveness of U.S. pharmaceutical companies and ultimately lower the cost of drug products. PUBLIC HEALTH RELEVANCE: The successful completion of the proposed R&D program will lead to the development of a quantitative instrument for monitoring the removal of toxic organic solvents from pharmaceutical products. The organic solvent mass flow meter will enable improved understanding of solvent drying kinetics and the development of efficient production processes based upon quality by design principles. This will result in fewer unacceptable batches and a more consistent, higher quality product which will be safer for public consumption.