【正文】 trolled exposure to the product during downstream operations. Biological Product This category includes therapeutic proteins generated by fermentation or cell culture and inactivated vaccines. The facility is to be designed in same way as API production, except that terminal sterilization is often not feasible, due to the fragility of the product. Live Virus Vaccines Vaccines containing a live virus, or viral vector, must be designed to provide containment of the organism to protect both operators and the environment. Viral vectors are viruslike particles that inject geic material into the cells of the organism being treated and are treated in a similar manner to live viruses. The biosafety level designated for the organism will drive decisions regarding the level of environmental controls that is required for the facility. Typically, these products require the use of adjuvants and will be suspension products, incapable of being filter sterilized. Products cannot be terminally sterilized. Live virus vaccine products can be campaigned in a multiproduct facility, as long as the vaccine production area is segregated from the remainder of the facility. Following the pletion of the live virus campaign, the suite will need to be pletely decontaminated prior to use for another product. Facility Types Single Product, Dedicated This facility is designed to produce a single product at any one time, throughout the year, without concern for crosscontamination with a second product. The facility can be operated to produce multiple products in a series of campaigns, converting between products. MuUiprociuct Multisuite This facility is designed to produce multiple products simultaneously in multiple sterile suites. Sterile operations in each suite are to be segregated from one another to ensure that crosscontamination is prevented. It is a remendation to clean and decontaminate any used ponents or equipment prior to exiting the suite and entering the return corridor. Production Area Description Conventional Aseptic Technology: Opeii In conventional ascptic processing, the product is exposed to the room environment during operation. For this reason, aseptic operations are required to be performed under ISO 5 ASEPTIC MANUFACTURING FACILITY DESIGN conditions, by sufficiently gowned operators, trained in aseptic technique. Sterility assurance levels for aseptic operations, including filling of vials or syringes, can be maximized through the use of barriers such as restricted access barrier systems or Isolators to limit the size of the aseptic environment and remove operators from the ISO 5 fill area. Tennhialli/ Sterilized Product Whenever possible, it is required to terminally sterilize filled units of product. Application of an overkill sterilization methodology can provide a sterility assurance level of 10_ 6, or better. Sterilization can be by steam, dry heat, gas, or radiation. Restricted Access Barrier: Open and Closed As defined by ISPE: A restricted access barrier system (RABS) is an advanced aseptic processing system that can be utilized in many applications in a fillfinish area. RABS provides an enclosed environment to reduce the risk of contamination to product, containers, closures, and product contact surfaces pared to the risks associated with conventional clean room operations. RABS can operate as doors closed for processing with very low risk of contamination similar to isolators, or permit rare open door interventions provided 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 sepa