【正文】 BUILDINGS AND FACILITIES 設(shè)計和結(jié)構(gòu) Design and Construction 用于中間體和原料藥生產(chǎn)的廠房和設(shè)施的選址、設(shè)計和建造應(yīng)當便于清潔，維護和適應(yīng)一定類型和階段的生產(chǎn)操作。 Buildings and facilities used in the manufacture of intermediates and APIs should be located, designed, and constructed to facilitate cleaning, maintenance, and operations as appropriate to the type and stage of manufacture. 廠房和設(shè)施應(yīng)有足夠空間，以便有秩序地放置設(shè)備和物料，防止混淆和污染。 Facilities should also be designed to minimize potential contamination. Where microbiological specifications have been established for the intermediate or API, facilities should also be designed to limit exposure to objectionable microbiological contaminants, as appropriate. 自身能對物料提供足夠保護的設(shè)備(如關(guān)閉的或封閉的系統(tǒng))，可以在戶外放置。 Buildings and facilities should have adequate space for the orderly placement of equipment and materials to prevent mixups and the equipment itself (., closed or contained systems) provides adequate protection of the material, such equipment can be located outdoors. 通過廠房和設(shè)施的物流和人流的設(shè)計應(yīng)當能防止混雜或污染。 The flow of materials and personnel through the building or facilities should be designed to prevent mixups or contamination. 以下活動應(yīng)當有指定區(qū)域或其它控制系統(tǒng)： There should be defined areas or other control systems for the following activities: 來料的接收、鑒別、取樣和待檢，等待放行或拒收。 Receipt, identification, sampling, and quarantine of ining materials, pending release or rejection 中間體和原料藥放行或拒收前的待驗；Quarantine before release or rejection of intermediates and APIs 中間體和原料藥的取樣；Sampling of intermediates and APIs 不合格物料處理(如退貨，返工或銷毀)前的貯存； Holding rejected materials before further disposition (., return, reprocessing or destruction) 已放行物料的貯存； Storage of released materials 生產(chǎn)操作 Production operations 包裝及貼簽簽操作；Packaging and labeling operations 實驗室操作。Laboratory operations 應(yīng)當為員工提供足夠和清潔的盥洗設(shè)施。這些盥洗設(shè)施應(yīng)當裝有冷熱水(視情況而定)、肥皂或洗滌劑，干手機和一次性毛巾。盥洗室應(yīng)當與生產(chǎn)區(qū)隔離，但要便于達到。應(yīng)當根據(jù)情況提供足夠的淋浴和/或更衣設(shè)施。 Adequate and clean washing and toilet facilities should be provided for personnel. These facilities should be equipped with hot and cold water, as appropriate, soap or detergent, air dryers, or single service towels. The washing and toilet facilities should be separate from, but easily accessible to, manufacturing areas. Adequate facilities for showering and/or changing clothes should be provided, when appropriate. 實驗室區(qū)域/操作通常應(yīng)當與生產(chǎn)區(qū)隔離。有些實驗室區(qū)域，特別是用于中間控制的，可以位于生產(chǎn)區(qū)內(nèi)，只要生產(chǎn)工藝操作對實驗室測量的準確性沒有負面影響，而且，實驗室及其操作對生產(chǎn)過程，或中間體，或原料藥也沒有負面影響。 Laboratory areas/operations should normally be separated from production areas. Some laboratory areas, in particular those used for inprocess controls, can be located in production areas, provided the operations of the production process do not adversely affect the accuracy of the laboratory measurements, and the laboratory and its operations do not adversely affect the production process, intermediate, or API. 公用設(shè)施 Utilities 對產(chǎn)品質(zhì)量會有影響的所有公用設(shè)施(如蒸汽，氣體，壓縮空氣和加熱，通風(fēng)及空調(diào)) 都應(yīng)當確認合格，并進行適當監(jiān)控，在超出限度時應(yīng)當采取相應(yīng)措施。應(yīng)當有這些公用設(shè)施的系統(tǒng)圖。 All utilities that could affect product quality (., steam, gas, pressed air, heating, ventilation, and air conditioning) should be qualified and appropriately monitored and action should be taken when limits are exceeded. Drawings for these utility systems should be available. 應(yīng)當根據(jù)情況，提供足夠的通風(fēng)、空氣過濾和排氣系統(tǒng)。這些系統(tǒng)應(yīng)當根據(jù)相應(yīng)的生產(chǎn)階段，設(shè)計和建造成將污染和交叉污染降至最低限度，并包括控制氣壓、微生物(如果適用)、灰塵、濕度和溫度的設(shè)備。 Adequate ventilation, air filtration and exhaust systems should be provided, where appropriate. These systems should be designed and constructed to minimize risks of contamination and crosscontamination and should include equipment for control of air pressure, microorganisms (if appropriate), dust, humidity, and temperature, as appropriate to the stage of manufacture. Particular attention should be given to areas where APIs are exposed to the environment. 如果空氣再循環(huán)到生產(chǎn)區(qū)域，應(yīng)當采取適當?shù)拇胧┛刂莆廴竞徒徊嫖廴镜娘L(fēng)險。 If air is recirculated to production areas, appropriate measures should be taken to control risks of contamination and crosscontamination. 永久性安裝的管道應(yīng)當有適宜的標識。這可以通過標識每根管道、提供證明文件、計算機控制系統(tǒng)，或其它替代方法來達到。管道的安裝處應(yīng)當防止污染中間體或原料藥。 Permanently installed pipework should be appropriately identified. This can be acplished by identifying individual lines, documentation, puter control systems, or alternative means. Pipework should be located to avoid risks of contamination of the intermediate or API. 排水溝應(yīng)當有足夠的尺寸，而且應(yīng)當根據(jù)情況裝有空斷器或適當?shù)难b置，防止倒虹吸。 Drains should be of adequate size and should be provided with an air break or a suitable device to prevent backsiphonage, when appropriate. 水 Water 原料藥生產(chǎn)中使用的水應(yīng)當證明適合于其預(yù)定的用途。 Water used in the manufacture of APIs should be demonstrated to be suitable for its intended use. 除非有其它理由，工藝用水最低限度應(yīng)當符合國際衛(wèi)生組織(WHO)的飲用水質(zhì)量指南。 Unless otherwise justified, process water should, at a minimum, meet World Health Organization (WHO) guidelines for drinking (potable) water quality. 如果飲用水不足以確保原料藥的質(zhì)量，并要求更為嚴格的化學(xué)和/或微生物水質(zhì)規(guī)格標準，應(yīng)當制定合適的物理/化學(xué)特性、微生物總數(shù)、控制菌和/或內(nèi)毒素的規(guī)格標準。If drinking (potable) water is insufficient to ensure API quality and tighter chemical and/or microbiological water quality specifications are called for, appropriate specifications for physical/chemical attributes, total microbial counts, objectionable organisms, and/or endotoxins should be established. 在工藝用水為達到規(guī)定質(zhì)量由制造商進行處理時，處理工藝應(yīng)當經(jīng)過驗證，并用合適的處置限度來監(jiān)測。 Where water used in the process is treated by the manufacturer to achieve a defined quality, the treatment process should be validated and monitored with appropriate action limits. 當非無菌原料藥的制造商打算或者聲稱該原料藥適用于進一步加工生產(chǎn)無菌藥品(醫(yī)療用品)時，最終分離和精制階段的用水應(yīng)當進行微生物總數(shù)、致病菌和內(nèi)毒素方面的監(jiān)測和控制。Where the manufacturer of a nonsterile API either intends or claims that it is suitable for use in further processing to produce a sterile drug (medicinal) product, water used in the final isolation and purification steps should be monitored and controlled for total microbial counts, objectionable organisms, and endotoxins. 限制 Containment 在高致敏性物質(zhì)，如青霉素或頭孢菌素類的生產(chǎn)中，應(yīng)當使用專用的生產(chǎn)區(qū)，包括設(shè)施、空氣處理設(shè)備和/或工藝設(shè)備。Dedicated production areas, which can include facilities, air handling equipment and/or process equipment, should be emp