Process Analytic Technologies (PAT) for Biologics

用于癌症治疗的生物药物的开发通常需要必须经过冻干的制剂来生产稳定的药物产品。开发药物配方和冷冻干燥过程的过程始于实验室实验，随后扩大到中试和生产规模的冻干机。早期配方和冻干工艺开发的主要挑战是可用于开发的活性药物成分的成本和有限供应，以及缺乏具有代表性的小型冻干机来模拟生产规模的干燥机。目前的实验室烘干机持有数百个小瓶和他们的操作和产品干燥行为与几个小瓶是不同的，因为高度非典型辐射传热满载的小瓶。在标准实验室干燥器中干燥几个小瓶所收集的过程信息是相对无用的。第一阶段SBIR项目的目标是设计、制造、测试和应用一种小型冻干机，该冻干机可以在大型生产冷冻干燥机通常遇到的传热传质条件下干燥一到七个产品瓶。迷你冻干机将配备工艺分析技术工具，使科学和工程原理能够成功地扩大工艺规模，并在经济上可行的药品生产。

The development of biologic drugs for cancer treatment often requires formulations that must be lyophilized to produce stable drug products. The process of developing a drug formulation and freeze-drying process begins with laboratory experiments followed by scaled-up to pilot and production scale lyophilizers. A major challenge during early formulation and lyophilization process development is the cost and limited supply of active pharmaceutical ingredient available for development and the lack of a representative small scale lyophilizer that emulates a production scale dryer. Current laboratory dryers hold hundreds of vials and their operation and product drying behavior with just a few vials is different than with a full load of vials due to highly atypical radiation heat transfer. The process information gathered drying a few vials in a standard laboratory dryer is relatively useless. The goal of this Phase I SBIR program is to design , fabricate, test, and apply a mini-lyophilizer that dries one to seven product vials under heat and mass transfer conditions typically encountered in larger production freeze dryers. The mini lyophilizer will be outfitted with process analytic technology tools that enable the use of scientific and engineering principles for successful process scale up and economically viable drug product manufacturing.