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

拟议项目是开发一种单位剂量连续冻干机， 在小分子和生物制品上展示其功能。冻干机的总体设计 已经完成了基于实验室数据和系统分析。设计 由三个主要室组成-成核和冷冻，初级干燥和二级干燥。 干燥-每个都与负载锁定系统连接，以防止回流和与 环境个体单位剂量将以真正连续的方式通过 工艺，其中工艺分析技术（PAT）将用于每个关键点，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 基因治疗产品将以灌装小瓶形式冻干，产品制剂为液体 形式连续进料到冻干机，并且完全测试的产品连续离开。规模 将达到每周50，000小瓶的水平，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，它可以很容易地扩展- 对于给定的运行低至单个小瓶。 拟议的项目直接符合外地住房安排的目标，包括解决所有 的目标，连续加工设备，自动化，在线PAT，和先进的 模拟和控制（基于模型）。该项目还具有满足国家需求的潜力 为先进制造业、工业设备设计和国内制造业， 除了对流行病的快速反应，消除冷链挑战， 工艺开发和将产品提供给患者所需的时间。 高级项目计划是：第1年，详细设计、实施和测试 加载锁定系统和小瓶悬挂轨道;第2年，全工艺的详细设计， 实施和初步测试，包括控制系统;第3年，完成PAT和模型- 并适用于实际药品和相关替代产品。 鉴于完成后实施的可能性，我们将定期沟通 通过我们在工业界的联系，从制药公司和制药公司 设备公司，用于各种规模的GMP版本的开发。

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.