Integrated Continuous Processing Facility for Small Molecule and Biologic Lyophilized Final Dosage Forms

拟议的项目是开发单位剂量连续冻干机，并 展示其在小分子和生物制品上的作用。冻干机的总体设计 已经在实验室数据和系统分析的基础上完成。设计 由三个主室组成--成核和冻结、一次干燥和二次干燥 烘干-每个都与加载锁定系统连接，以防止回流和与 环境。单个单位剂量将真正连续地通过 流程，其中将在每个关键点采用流程分析技术(PAT)；以及 基于模型的控制将用于完全自动化。在项目结束时，疫苗和 基因治疗产品将在液体中作为装满产品配方的小瓶进行冷冻干燥 表格不断地被送到冻干机中，完全测试的产品不断地退出。比例尺 将达到每周50,000瓶的水平，这是中型到大型的商业规模- 批量生产。然而，设备的概念是这样的，它可以很容易地进行扩展- 对于给定的运行，最低可达一瓶。 拟议的项目直接符合RFA的目标，包括解决所有 连续加工设备、自动化、在线PAT和高级 仿真和控制(基于模型)。该项目还具有满足国家需求的潜力。 先进制造、工业设备设计和国内制造，在 除了对流行病做出快速反应，消除冷链挑战，并减少 流程开发和将产品送到患者手中所需的时间。 高级项目计划是：第1年，详细设计、实施和测试 装载锁紧系统和小瓶悬挂轨道；第二年，全流程详细设计， 实施和初步测试，包括控制系统；第3年，最终确定PAT和模型- 基于控制，并适用于实际药品和相关替代产品。 鉴于可能在完成后实施，我们将保持定期沟通 与我们在行业中的联系人，来自制药公司和制药公司 设备公司，用于开发各种规模的GMP版本。

The proposed project is to develop a unit dose continuous lyophilizer and to demonstrate its function on small molecule and biologics. The overall design of the lyophilizer has already been accomplished based on laboratory data and systems analysis. The design consists of three main chambers – nucleation and freezing, primary drying, and secondary drying – each connected with a load-lock system to prevent back-flow and interaction with the environment. Individual unit doses will be fed in a truly continuous manner through the process, in which process analytical technology (PAT) will be employed at each key point, and model-based control will be used for full automation. At the end of the project, vaccines and gene therapy products will be lyophilized as filled vials with the product formulation in liquid form are continuously fed to the lyophilizer and fully tested product continuously exits. Scale will be at the 50,000 vial per week level, which is commercial scale for a medium to large- volume product. However, the concept of the equipment is such that it could be easily scaled- down to as low as a single vial for a given run. The proposed project directly fits into the objectives of the RFA, including addressing all of the objectives, continuous processing equipment, automation, in-line PAT, and advanced simulation and control (model-based). The project also has the potential to meet national needs for advanced manufacturing, industrial equipment design and domestic manufacturing, in addition to fast responses to epidemics, eliminating cold-chain challenges, and reducing the amount of time needed for process development and getting products to patients. The high-level project plan is: Year 1, detailed design, implementation, and testing of load-lock system and vial suspension track; Year 2, detailed design of full process, implementation, and initial testing, including control system; Year 3, finalize PAT and model- based control and apply to actual pharmaceutical products and relevant surrogate products. Given the potential for implementation upon completion, we will be in regular communication with our contacts in industry, from both pharmaceutical companies and pharmaceutical equipment companies, for development of GMP versions at various scales.