Sterile formulation 619 to people. One of the most important facility design factors is in the isolation of product from its surrounding environment. Within the constraints of product quality, prevention of bacterial and particulate matter contamination should dominate the design concept and selection of equipment When product is exposed, air quality should be Class 100* or better which can be achieved by High Efficiency Particulate Air(HEPa)filtration Documentation of initial HEPA certification and periodic test results should be available at all times. Air pressure balancing should provide air flow from clean to less clean areas. Temperature and humidity are properties important to control in order to minimize the potential for microbial growth within the constraints of impact on product. Frequent rotation of sanitizing agents reduces the potential development of resistant organisms. Environmental monitoring is required to verify that product protection systems are working as expected. Environmental and safety concerns have reduced the practical ity of ethylene oxide sterilization while other methods such as peracetic acid and VPHP (vapor pressure hydrogen peroxide)are currently being explored as sterilant 4.0 CRYSTALLIZATION Crystallizers should have variable speed agitators, temperature con- trol, and sterilizable vent filters. As many controls as possible should be located outside of the sterile area. The crystallization vessel should be located as close to the filtration unit as possible. Time, temperature, and agitation speed are critical variables that may need strict control during the crystalli zation process. The crystallization vessel should be part of a closed system and often is jacketed for glycol temperature control 5.0 FILTERING/DRYING The filtration unit can be a centrifuge or closed filter that is either a pressure or vacuum unit. Some processes may require solution washing of the crystalline product. Facility design should therefore be optimized for flexibility. Recent pressure/vacuum filtration units can perform several functions such as collection washing with appropriate solvents, solution washing, and drying of a crystalline product. These filter/dryer units offer the advantage of a closed system that protects product from people and vice *Class 100 means no more than 100 particles per cubic foot greater than or equal to 0.5 micrometersSterile Formulation 61 9 to people. One ofthe most important facility design factors is in the isolation of product from its surrounding environment. Within the constraints of product quality, prevention of bacterial and particulate matter contamination should dominate the design concept and selection of equipment. When product is exposed, air quality should be Class 100* or better, which can be achieved by High Efficiency Particulate Air (HEPA) filtration. Documentation of initial HEPA certification and periodic test results should be available at all times. Air pressure balancing should provide air flow from clean to less clean areas. Temperature and humidity are properties important to control in order to minimize the potential for microbial growth within the constraints of impact on product. Frequent rotation of sanitizing agents reduces the potential development of resistant organisms. Environmental monitoring is required to verify that product protection systems are working as expected. Environmental and safety concerns have reduced the practical￾ity of ethylene oxide sterilization while other methods such as peracetic acid and VPHP (vapor pressure hydrogen peroxide) are currently being explored as sterilants. 4.0 CRYSTALLIZATION Crystallizers should have variable speed agitators, temperature con￾trol, and sterilizable vent filters. As many controls as possible should be located outside ofthe sterile area. The crystallization vessel should be located as close to the filtration unit as possible. Time, temperature, and agitation speed are critical variables that may need strict control during the crystalli￾zation process. The crystallization vessel should be part of a closed system and often is jacketed for glycol temperature control. 5.0 FILTERING/DRYING The filtration unit can be a centrifuge or closed filter that is either a pressure or vacuum unit. Some processes may require solution washing of the crystalline product. Facility design should therefore be optimized for flexibility. Recent pressurehacuum filtration units can perform several functions such as collection washing with appropriate solvents, solution washing, and drying of a crystalline product. These filteddryer units offer the advantage of a closed system that protects product from people and vice *Class 100 means no more than 100 particles per cubic foot greater than or equal to 0.5 micrometers