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: 10629817
• 负责人: BERNHARDT L TROUT
• 金额: $ 25万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10629817
• 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.

拟议项目是开发一种单位剂量连续冻干机并 展示其在小分子和生物制剂上的功能。冻干机的总体设计 基于实验室数据和系统分析已经完成。设计 由三个主要室组成 - 成核和冷冻室、初级干燥室和二级干燥室 干燥——每个都与负载锁定系统连接，以防止回流和与干燥剂相互作用 环境。单个单位剂量将以真正连续的方式通过 过程中，每个关键点都会采用过程分析技术（PAT），以及 基于模型的控制将用于完全自动化。项目结束时，疫苗和 基因治疗产品将被冻干为装有液体产品配方的小瓶 形式连续送入冻干机，经过充分测试的产品连续退出。规模 将达到每周 50,000 瓶的水平，这是大中型企业的商业规模 批量产品。然而，该设备的概念是可以轻松扩展- 对于给定的运行，低至单个小瓶。 拟议的项目直接符合 RFA 的目标，包括解决所有问题 目标、连续加工设备、自动化、在线 PAT 和先进的 仿真和控制（基于模型）。该项目还有潜力满足国家需求 面向先进制造、工业装备设计和国内制造， 除了快速应对流行病、消除冷链挑战、减少 工艺开发和将产品提供给患者所需的时间。 高层项目计划是： 第一年，详细设计、实施和测试 负载锁定系统和小瓶悬挂轨道；第2年，全流程详细设计， 实施和初始测试，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。 鉴于完成后实施的潜力，我们将定期沟通 凭借我们在制药公司和制药公司的行业联系 设备公司，用于开发各种规模的 GMP 版本。