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

用于小分子和生物冻干最终剂型的集成连续加工设备

• 批准号: 10238814
• 负责人: BERNHARDT L TROUT
• 金额: $ 60.86万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238814
• 关键词: Integrated; Continuous; Processing; Facility; Small

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.

拟议的项目是开发单位剂量连续的冻干剂和 展示其在小分子和生物制剂上的功能。冻干器的整体设计 已经基于实验室数据和系统分析来完成。设计 由三个主腔室组成 - 成核和冷冻，初级干燥和次要 干燥 - 每个与负载锁系统连接，以防止后流并与 环境。单个单位剂量将以真正连续的方式通过 过程，在每个关键点将雇用过程分析技术（PAT），以及 基于模型的控制将用于完整自动化。在项目结束时，疫苗和 基因治疗产物将被冻干为液体中的产物配方的填充小瓶 形式连续喂入冻干剂，并连续出口全面测试的产品。规模 将处于每周50,000个小瓶的水平，这是中等至大型的商业规模 音量产品。但是，设备的概念使得可以很容易地缩放 - 在给定的运行中低至单个小瓶。 拟议的项目直接适合RFA的对象，包括解决所有问题 目标，连续处理设备，自动化，在线PAT和高级 模拟和控制（基于模型）。该项目还有可能满足国家需求 用于高级制造，工业设备设计和国内制造业 除了快速回应情节，消除冷链挑战并减少 过程开发和将产品送入患者所需的时间。 高级项目计划是：1年，详细的设计，实施和测试 负载锁系统和小瓶悬架轨道；第二年，完整过程的详细设计， 实施和初始测试，包括控制系统；第三年，最终确定PAT和模型 - 基于控制并应用于实际的药品和相关的替代产品。 鉴于完成后实施的潜力，我们将进行定期沟通 通过我们的行业联系，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。