FDA指南——注射用冻干.pdfVIP

Inspection Guides Lyophilization of Parenteral (7/93) 1/ 17 Lyophilization of Parenteral (7/93) GUIDE TO INSPECTIONS OF LYOPHILIZATION OF PARENTERALS 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). INTRODUCTION 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). The advantages of lyophilization include: Ease of processing a liquid, which simplifies aseptic handling Enhanced stability of a dry powder Removal of water without excessive heating of the product Enhanced product stability in a dry state Rapid and easy dissolution of reconstituted product Disadvantages of lyophilization include: Increased handling and processing time Need for sterile diluent upon reconstitution Cost and complexity of equipment The lyophilization process generally includes the following steps: • Dissolving the drug and excipients in a suitable solvent, generally water for injection (WFI). • Sterilizing the bulk solution by passing it through a 0.22 micron bacteria-retentive filter. • Filling into individual sterile containers and partially stoppering the containers under aseptic conditions. • Transporting the partially stoppered containers to the lyophilizer and loading into the chamber under aseptic conditions. • Freezing the solution by placing the partially stoppered containers on cooled shelv