Organic Solvent Vapor Mass Flow Rate Monitor for Pharmaceutical Drying Operations

描述（由申请人提供）：本I期SBIR研发提案的目标是开发一种溶剂蒸气质量流量监测仪器，该仪器将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过程，支持FDA QbD计划。药品的生产，包括治疗癌症的药物，通常需要使用有机溶剂的化学加工技术。虽然水是首选的溶剂，但许多药品生产时使用的是有毒的有机溶剂，在最终灌装/完成操作之前必须从产品中去除这些溶剂。从固体形式产品中去除溶剂通常包括相分离步骤，随后是干燥步骤，在此过程中，通过应用热能去除溶剂蒸汽。干燥操作的例子包括真空干燥或流化床干燥。或者，不稳定药品的冷冻干燥包括用液体产品（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，过程开发和过程监测都将受益于过程分析技术（PAT）工具，该工具可以连续、实时地监测溶剂质量去除率。目前，还没有PAT工具提供这种重要的监视功能。在拟议的第一阶段研发计划中，物理科学公司将进行实验调查，以证明开发有机溶剂蒸汽质量流量计的可行性。有机溶剂质量流量计的成功开发将通过质量平衡测定提高工艺理解和放大。这将提高药品生产和产品质量，降低生产成本。这将提高美国制药公司的竞争力，并最终降低药品成本。

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.