注射用粉针的冻干法检查指南.docVIP

PAGE PAGE 1 GUIDE TO INSPECTIONS OF LYOPHILIZATION OF PARENTERALS 注射用粉针的冻干法检查指南 Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s). 注：此文件为调查员和FDA其它人员的参考资料。它不对FDA产生约束，亦没有给任何人员提供权利、特权、利益或豁免权。 INTRODUCTION/引言 Lyophilization or freeze drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. The process consists of three separate, unique, and interdependent processes; freezing, primary drying (sublimation), and secondary drying (desorption). 冻干法是一种工艺程序，在这一工艺过程中，通过真空冷冻，去除产品中的水分，冰块直接从固体转变为蒸汽状态而无需经过液体阶段。这一工艺由单独、唯一和相互依存的三个步骤构成，即冷冻、一次干燥（升华）和二次干燥（解吸）。 The advantages of lyophilization include: 冻干法的优点包括： Ease of processing a liquid, which simplifies aseptic handling 容易对液体进行加工处理，简化无菌操作 Enhanced stability of a dry powder 提高干粉的稳定性 Removal of water without excessive heating of the product 无需对产品进行过多的加热便可去除水分 Enhanced product stability in a dry state 提高产品在干燥状态的稳定性 Rapid and easy dissolution of reconstituted product 产品可快速并易于溶解 Disadvantages of lyophilization include: 冻干法的缺点包括： Increased handling and processing time 增加处理和加工的时间 Need for sterile diluent upon reconstitution 溶解时需无菌稀释剂 Cost and complexity of equipment 设备复杂，成本较高 The lyophilization process generally includes the following steps: 冻干工艺通常包含下列步骤： o Dissolving the drug and excipients in a suitable solvent, generally water for injection (WFI). 用一种合适的溶剂来溶解药物和赋形剂，通常为注射用水。 o Sterilizing the bulk solution by passing it through a 0.22 micron bacteria-retentive filter. 通过0.22微米的细菌截留过滤器对散装溶液进行灭菌。 o Filling into individual sterile containers and partially stoppering the containers under aseptic conditions. 在无菌条件下，将溶液灌装到无菌容器中并对容器进行半压塞。 o Transporting the partially stoppered containers to the lyophilizer and loading into the chamber under as