【正文】 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(dāng)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。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(dāng)經(jīng)過驗證，并用合適的處置限度來監(jiān)測。 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(dāng)符合國際衛(wèi)生組織(WHO)的飲用水質(zhì)量指南。 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(dāng)有足夠的尺寸，而且應(yīng)當(dāng)根據(jù)情況裝有空斷器或適當(dāng)?shù)难b置，防止倒虹吸。這可以通過標(biāo)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。 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(dāng)采取適當(dāng)?shù)拇胧┛刂莆廴竞徒徊嫖廴镜娘L(fēng)險。 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(dāng)根據(jù)情況，提供足夠的通風(fēng)、空氣過濾和排氣系統(tǒng)。 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(dāng)確認合格，并進行適當(dāng)監(jiān)控，在超出限度時應(yīng)當(dāng)采取相應(yīng)措施。 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(dāng)與生產(chǎn)區(qū)隔離。盥洗室應(yīng)當(dāng)與生產(chǎn)區(qū)隔離，但要便于達到。Laboratory operations 應(yīng)當(dāng)為員工提供足夠和清潔的盥洗設(shè)施。 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(dāng)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。 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。 Records should be maintained stating the name, address, qualifications, and type of service provided by these consultants.4 建筑和設(shè)施 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(dāng)便于清潔，維護和適應(yīng)一定類型和階段的生產(chǎn)操作。s inclusion would not jeopardize the safety or quality of the APIs. 顧問 Consultants 中間體或原料藥生產(chǎn)和控制的顧問應(yīng)當(dāng)有足夠的學(xué)歷，受訓(xùn)和經(jīng)驗，能勝任所承擔(dān)的工作。在任何時候(經(jīng)醫(yī)學(xué)檢驗或監(jiān)控檢查)任何患有危及到原料藥質(zhì)量的疾病或創(chuàng)傷的人員都不應(yīng)當(dāng)參與作業(yè)，直到健康狀況已恢復(fù)，或者有資格的醫(yī)學(xué)人員確認該員工不會危及到原料藥的安全性和質(zhì)量。 Personnel should avoid direct contact with intermediates or APIs. 吸煙、吃、喝、咀嚼及存放食品僅限于與生產(chǎn)區(qū)隔開的指定區(qū)域。其它保護性用品如頭、臉、手和臂等遮護用品必要時也應(yīng)當(dāng)佩帶，以免原料藥和中間體受到污染。s functions. Records of training should be maintained. Training should be periodically assessed. 員工的衛(wèi)生 Personnel Hygiene 員工應(yīng)當(dāng)養(yǎng)成良好的衛(wèi)生和健康習(xí)慣。培訓(xùn)記錄應(yīng)當(dāng)保存，并應(yīng)當(dāng)定期對培訓(xùn)進行評估。 There should be an adequate number of personnel qualified by appropriate education, training, and/or experience to perform and supervise the manufacture of intermediates and APIs. 參與原料藥和中間體生產(chǎn)的所有人員的職責(zé)應(yīng)當(dāng)書面規(guī)定。獲準(zhǔn)的整改措施應(yīng)當(dāng)及時、有效地完成。 穩(wěn)定性監(jiān)測結(jié)果的審核； A review of results of the stability monitoring program 所有與質(zhì)量有關(guān)的退貨、投訴和召回的審核； A review of all qualityrelated returns, plaints and recalls 整改措施的適當(dāng)性的審核； A review of adequacy of corrective actions 應(yīng)當(dāng)對質(zhì)量審核結(jié)果進行評估，并做出是否需要整改或做任何再驗證的評價。 Audit findings and corrective actions should be documented and brought to the attention of responsible management of the firm. Agreed corrective actions should be pleted in a timely and effective manner. 產(chǎn)品質(zhì)量審核 Product Quality Review 原料藥的定期質(zhì)量審核應(yīng)當(dāng)以證實工藝的一致性為目的來進行。 To verify pliance with the principles of GMP for APIs, regular internal audits should be performed in accordance with an approved schedule. 審計結(jié)果及整改措施應(yīng)當(dāng)形成文件，并引起公司責(zé)任管理人員的重視。 Reviewing all production batch records and ensuring that these are pleted and signed4. 確保所有的生產(chǎn)偏差都已報告、評價，對關(guān)鍵的偏差已做了調(diào)查，并記錄結(jié)論； Making sure that all production deviations are reported and evaluated and that critical deviations are investigated and the conclusions are recorded5. 確保生產(chǎn)設(shè)施的清潔，必要時要消毒； Making sure that production facilities are clean and, when appropriate, disinfected6. 確保進行必要的校驗，并有記錄； Making sure that the necessary calibrations are performed and records kept7. 確保對廠房和設(shè)備進行保養(yǎng)，并有記錄； Making sure that the premises and equipment are maintained and records kept8. 確保驗證計劃、方案和報告的審核和批準(zhǔn)； Making sure that validation protocols and reports are r