Sterile formulation 617 filtration, isolation, filling, and environmental conditions required for asep tic processing 2.0 STERILE BULK PREPARATION The solutions used for the dissolution of injectable products are prepared by using Water for Injection (WFI USP that has been made as described in Ch 13 of this handbook. In some cases, solutions are prepared using organic solvents(e.g, acetone, methanol, ethanol, isopropanol) alone or in combination with WFI. The potential for preventing microbial contamination should dominate the delivery and storage systems for water and solvents a typical solution system will consist of a dissolution vessel, a sterile filtration transfer line, and a vessel to hold the sterile filtered solution prior to further processing. Dissolution areas tend to have Class 100,000* air quality with smooth, easy-to-clean surfaces. The sterile side of the system should have the capability of being cleaned and steam sterilized in place or easily dismantled for cleaning and sterilization. [o normally, type 316 stainless steel can be used throughout the facility unless process condition dictate otherwise. Passivation of welds will minimize the potential for microbial growth at rough edges. Metal particulates should be a concern when welding into the processing system. Computer automated systems tend to be the method of choice for validated cleaning and sterilizing operations The solution filtration system should have a prefilter and final steril- ization filter. The selection of filters is dependent on the type of solutions to be filtered. The sterile filters should be validated for the intended use with the product/solution systems. Sterile filters for gases(air or nitrogen)need to be discussed with filter manufacturers to ensure that pressure ratings are appropriate with the intended use. Appropriate pressure regulation of ancillary systems should always be a design consideration. vent filters will be needed in the processing system to maintain sterility during transfe operations. Filter integrity testing(e.g, bubble point or diffusion testing)is quired to ensure that filters remain functional after their usage. Redundan cy of filters will provide a greater safety factor for product during manufac- turing operations. Sterilization of diaphragm valves tends to present fewer concerns with microbial penetration compared to ball type valves. The number of connections should be kept to a minimum. Thread-fitted piping Class 100,000 means no more than 100,000 particles per cubic foot greater than or equal to 0.5 micrometersSterile Formulation 61 7 filtration, isolation, filling, and environmental conditions required for asep￾tic processing. 2.0 STERILE BULK PREPARATION The solutions used for the dissolution of injectable products are prepared by using Water for Injection (WFI) USP that has been made as described in Ch. 13 of this handbook. In some cases, solutions are prepared using organic solvents (e.g., acetone, methanol, ethanol, isopropanol) alone or in combination with WFI. The potential for preventing microbial contamination should dominate the delivery and storage systems for water and solvents. A typical solution system will consist of a dissolution vessel, a sterile filtration transfer line, and a vessel to hold the sterile filtered solution prior to fbrther processing. Dissolution areas tend to have Class 100,000* air quality with smooth, easy-to-clean surfaces. The sterile side of the system should have the capability of being cleaned and steam sterilized in place or easily dismantled for cleaning and sterilization.[l01 Normally, type 316 stainless steel can be used throughout the facility unless process conditions dictate otherwise. Passivation of welds will minimize the potential for microbial growth at rough edges. Metal particulates should be a concern when welding into the processing system. Computer automated systems tend to be the method of choice for validated cleaning and sterilizing operations. The solution filtration system should have a prefilter and final steril￾ization filter. The selection of filters is dependent on the type of solutions to be filtered. The sterile filters should be validated for the intended use with the productholution systems. Sterile filters for gases (air or nitrogen) need to be discussed with filter manufacturers to ensure that pressure ratings are appropriate with the intended use. Appropriate pressure regulation of ancillary systems should always be a design consideration. Vent filters will be needed in the processing system to maintain sterility during transfer operations. Filter integrity testing (e.g., bubble point or diffision testing) is required to ensure that filters remain fbnctional after their usage. Redundan￾cy of filters will provide a greater safety factor for product during manufac￾turing operations. Sterilization of diaphragm valves tends to present fewer concerns with microbial penetration compared to ball type valves. The number of connections should be kept to a minimum. Thread-fitted piping * Class 100,000 means no more than 100,000 particles per cubic foot greater than or equal to 0.5 micrometers