626 Fermentation and Biochemical Engineering Handbook Freeze dried vials are usually partially stoppered just before entering the dryer. Closures are seated into the vials mechanically at the end of the drying cycle. A typical freeze drying flow diagram is shown in Fig. 6 NON- STERILE NONSTERILE STERILE AREA REA SOLUTION IN FIGURE T CON VEYER LIOU CAPPER FILL FREEZE DRYER 7STOPPER Figure 6. Sterile freeze drying operation 12.0 ENVIRONMEN The term environment in sterile product manufacture means more than air quality and surface cleanliness. Other environmental concems include water systems, compressed air and gas systems, temperature and humidity control, and the monitoring of personnel There are at least four classified areas in sterile bulk manufacturing, each with different requirements for cleanliness: aseptic, controlled clean, clean, and general Good Manufacturing Practice regulations(1)(211 42(c)10)require floors, walls, and ceilings to be smooth and easily cleanable. Temperature and humidity should be controlled, The air supply is filtered through high efficiency particulate air(HEPA)filters, and systems are used to monitor environmental conditions, cleaning and disinfecting the room, and equipment product aseptic conditions. Federal Standard 209E(5) and The European Community Guide to Good Manufacturing Practice for Medicinal Products EC-CGMP)6l provide air classifications for the manufacture of sterile products. A recent information section in the USP has proposed similar microbial quality standards for clean room(see Table 1)626 Fermentation and Biochemical Engineering Handbook J I L L 1 Freeze dried vials are usually partially stoppered just before entering the dryer. Closures are seated into the vials mechanically at the end of the drymg cycle. A typical freeze drying flow diagram is shown in Fig. 6. * CONVEYER 7 ST~LE AREa -L . U L ; CAPPER d + d SOLUTION t4 STERILE AREA L. ti I I . FREEZE DRYER H // 'ISTOPPER Figure 6. Sterile freeze drying operation 12.0 ENVIRONMENT The term environment in sterile product manufacture means more than air quality and surface cleanliness. Other environmental concerns include water systems, compressed air and gas systems, temperature and humidity control, and the monitoring of personnel. There are at least four classified areas in sterile bulk manufacturing, each with different requirements for cleanliness: aseptic, controlled clean, clean, and general. Good Manufacturing Practice regulations (1) (2 1 1.42(c) 10) require floors, walls, and ceilings to be smooth and easily cleanable. Temperature and humidity should be controlled. The air supply is filtered through high￾efficiency particulate air (HEPA) filters, and systems are used to monitor environmental conditions, cleaning and disinfecting the room, and equipment product aseptic conditions. Federal Standard 209E[I51 and The European Community Guide to Good Manufacturing Practice for Medicinal Products (EC-CGMP)[I61 provide air classifications for the manufacture of sterile products. A recent information section in the USP has proposed similar microbial quality standards for clean room (see Table 1)