【正文】 number of products to be manufactured and the xiv CONTRIBUTORS production campaign strategy will impact the facility design. Product Types Chemical Bulk Drug Substances (API) Sterile chemical bulk drug substances are derived from chemical reactions. Facilities producing sterile API will be required to provide protection of the product during synthesis, isolation, and bulk filling. An adjuvant produced by precipitation is an example of a sterile API. Potent Compounds Potent pounds are classified as those chemical drug substances that are considered to be toxic to human s when exposure limits are exceeded, and may cause allergic reactions, birth defects, cancer, or other conditions. For this reason, it is required to ensure protection of operators working with potent pounds, ensure containment of all operations, and prevent release of products into the environment. It is acceptable to permit production of potent pounds in multiproduct facilities, provided the suite is segregated from other operations.2 VOLUME 2: FACILITY DESIGN, STERILIZATION AND PROCESSING Following filling, it is remended to wash the exterior of vials produced in potent pound facilities to limit uncontrolled exposure to the product during downstream operations. Antibiotics Antibiotics are drugs produced to treat bacterial or fungal infections. Antibiotics are considered to be sensitizers and can generate mild to severe allergic reactions in patients and operators. It is required to segregate production operations from personnel outside the production area. Campaigns of antibiotic must be segregated from other products, as the potential for crosscontamination between products can occur. In addition, plactam (penicillin) and nonpenicillin based (cephalosporin) antibiotic products are not permitted to be produced in the same facility, as there is evidence that intolerance can occur for one antibiotic type, and not another. To acplish this segregation, it is a requirement that a separate dedicated suite be constructed for each antibiotic family. This suite can be housed inside a mon structure with other functions. At no time should antibiotic production personnel e into contact with personnel operating in media or fermentation areas while gowned. Following filling, it is remended to wash the exterior of vials produced in antibiotic facilities to limit uncontrolled 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 p