【正文】 rovided appropriate measures are taken (11). In representative installations recently constructed, there is a wide variety of equipment configurations referred to as KABSs. In construction detail, some approximate isolators in their level of segregation of the clean environment from the background environment, while other examples employ less rigorous segregation between the clean environment and the background room. When barrier doors are required to be opened, the opening must be protected within an ISO 5 zone, to the extent necessary to ensure continuous ISO 5 coverage. The door must be permitted to be opened without leaving the ISO 5 zone. Isolation Technology As defined by ISPE: An isolator is a leaktight enclosure designed to protect operators from hazardous/potent processes or protect processes from people or detrimental external environments or both. A basic enclosure consists of a shell, viewing window, glove/sleeve assemblies, supply and exhaust filters, light (s), gauge (s), input and output openings (equipment door airlocks, RTPs, etc.), and various other perations. There are two types of isolators: Closed isolators. Isolators operated as closed systems do not exchange unfiltered air or contaminants with adjacent environments. Their ability to operate without personnel access to the critical zone makes isolators capable of levels of separation between the internal and external environment unattainable with other technologies. Because the effectiveness of this separation, closed isolators are ideally suited for application in the preparation of sterile and/or toxic material. Aseptic and containment isolators are two types of closed isolators. Open isolators. Open isolators differ from closed isolators in that they are designed to allow for the continuous or semicontinuous egress of materials during operation while maintaining a level of protection over the internal environment. Open isolators are decontaminated while closed, and then opened during manufacturing. Open isolators typically are used for the aseptic filling of finished pharmaceuticals (11). Closed Processing Closed system sterile processing. A closed system is one that does not contain any open aseptic manipulations or interventions by design or operation and does not allow microbial ingress. Validated sterilization cycles must be provided. The product is separated from the surrounding room environment by a sterilizing grade vent filters. Leak testing must occur pre and post use to demonstrate the system integrity. EQUIPMENT AND PROCESS SYSTEM IMPACT ON FACILITY It is important to start the facility design with an understanding of each process step involved with the manufacture of a sterile product. In this section, an overview is provided for some of the more mon process steps, including a description of the major equipment, material flows, and facility impacts. Nonactive Materials Nonactive materials are transported from the warehouse to the weigh/dispense area, where they are dispensed VOLUME 2: FACILITY DESIGN. STERILIZATION AND PROCESSING into containers under a hood with high efficiency particulate air (HEPA) filtration. The hoods used in the dispensing operation shall be designed for protection of the product and may also need to protect the operator from exposure to potentially hazardous materials used in the formulation process. The number of hoods, and type, will be determined by evaluating the number of weighing operations that must be performed, the size of the weighing operations, the patibility of materials that must be weighed, and any special ergonomic or personnel safely concerns. Materials that are not patible may need to be dispensed in separate hoods to prevent any crosscontamination concerns. Also, dispensing operations involving large bulk containers will require either a lift assist or pallet jack access to prevent operator injury, requiring the hood to be designed as a walkin typo. Hoods being designed for product protection typically recirculate air back to the dispensing room to reduce the HVAC consumption for the area. However, when weighing hazardous materials, the air from the hood may need to be captured and exhausted to the roof through some type of environmental control device. Hoods of this type are typically designed to be negatively pressurized with respect to the dispensing room. Containers may be either singleuse or reusable. Singleuse containers are disposable. Reusable containers are required to be tracked and controlled to prevent crosscontamination of clean and used containers. Prior to reuse, used containers should be brought to a parts preparation washroom for cleaning and then placed in controlled storage. Nonactive materials are dispensed into bags or plastic bottles and can be placed into plastic bins as part of preassembled kits. Preweighed nonactive materials are stored as kits and staged until they are ready to be transferred to the formulation area. Identifying labels should be placed on the containers. It is typical to provide a local WFI drop feeding a sink in the weigh/dispense area, with WFI temperature controlled by a local WFI drop cooler. The WFI drop is periodically flushed and sampled per SOP. WFI is used to prepare solutions of nonactive materials in bottles. This operation may bo performed with equipment such as a laboratory agitator. Bench scales are used for dispensing of smallerscale materials. Floor scales are used for larger quantities. Balances and measuring equipment should be of an appropriate range and precision. Active Materials Receipt/Storage Active materials, API or drug substance (DS), may be received in a wide variety of container types, in either frozen or liquid form, or as a solid. Careful consideration should be given to the form and container type, since this affects the storage, transport, prepar