【正文】 生產(chǎn)中間體和原料藥的廠房應(yīng)當適當?shù)乇ｐB(yǎng)、維修并保持清潔。 衛(wèi)生和保養(yǎng) Buildings used in the manufacture of intermediates and APIs should be properly maintained and repaired and kept in a clean condition. Sanitation and Maintenance 進入和流出廠房及鄰近區(qū)域的污水、垃圾和其它廢物（如生產(chǎn)中的固態(tài)、液態(tài)或氣態(tài)的副產(chǎn)物），應(yīng)當安全、及時、衛(wèi)生的處理。 排污和垃圾 Sewage, refuse, and other waste (., solids, liquids, or gaseous byproducts from manufacturing) in and from buildings and the immediate surrounding area should be disposed of in a safe, timely, and sanitary manner. Containers and/or pipes for waste material should be clearly identified. 所有區(qū)域都應(yīng)當提供充足的照明，以便于清洗、保養(yǎng)或其它操作。 Lighting 劇毒的非藥用物質(zhì)，如除草劑、殺蟲劑的任何生產(chǎn)活動（包括稱重、研磨或包裝）都不應(yīng)當使用生產(chǎn)原料藥所使用的廠房和/或設(shè)備。 Appropriate measures should be established and implemented to prevent crosscontamination from personnel and materials moving from one dedicated area to another. 應(yīng)當建立并實施相應(yīng)的措施，防止由于在各專用區(qū)域間流動的人員和物料而造成的交叉污染。 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。 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. 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. If drinking (portable) 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. Unless otherwise justified, process water should, at a minimum, meet World Health Organization (WHO) guidelines for drinking (portable) water quality. 水 Water used in the manufacture of APIs should be demonstrated to be suitable for its intended use. Water Drains should be of adequate size and should be provided with an air break or a suitable device to prevent backsiphonage, when appropriate.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。 Permanently installed pipework should be appropriately identified. This can be acplished by identifying individual lines, documentation, puter control system, or alternative means. Pipework should be located to avoid risks of contamination of the intermediate or ApI.特別值得注意的是原料藥暴露的區(qū)域。 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)。應(yīng)當有這些公用設(shè)施的系統(tǒng)圖。 Utilities 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. 實驗室區(qū)域/操作通常應(yīng)當與生產(chǎn)區(qū)隔離。盥洗室應(yīng)當與生產(chǎn)區(qū)隔離，但要便于達到。 應(yīng)當為員工提供足夠和清潔的盥洗設(shè)施。 There should be defined areas or other control systems for the following activities: 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。 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。 Buildings and facilities should have adequate space for the orderly placement of equipment and materials to prevent mixups and contamination.設(shè)施的設(shè)計應(yīng)盡量減少潛在的污染。 4. 建筑和設(shè)施 Design and Construction Records should be maintained stating the name, address, qualifications, and type of service provided by these consultants. 顧問的姓名、地址、資格和提供服務(wù)的類型都應(yīng)當有文字記錄。 顧問 Consultants advising on the manufacture and control of intermediates or APIs should have sufficient education, training, and experience, or any bination thereof, to advise on the subject for which they are retained.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。 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。 員工應(yīng)當避免與中間體或原料藥的直接接觸。 Personnel should avoid direct contact with intermediates and APIs. 員工應(yīng)當穿著適合其所從事生產(chǎn)操作的干凈服裝，必要時應(yīng)當更換。 Personnel should wear clean clothing suitable for the manufacturing activity with which they are involved and this clothing should be changed, when appropriate. Additional protective apparel, such as head, face, hand, and arm coverings, should be worn, when necessary, to protect intermediates and APIs from contamination.培訓(xùn)記錄應(yīng)當保存，并應(yīng)當定期對培訓(xùn)進行評估。 參與原料藥和中間體生產(chǎn)的所有人員的職責(zé)應(yīng)當書面規(guī)定。 The responsibilities of all personnel engaged in the manufacture of intermediates and APIs should be specified in writing. 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.3. PERSONNEL獲準的整改措施應(yīng)當及時、有效地完成。應(yīng)當對質(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。 整改措施的適當性的審核。 所有與質(zhì)量有關(guān)的退貨、投訴和召回的審核； 穩(wěn)定性監(jiān)測的審核； 任何工藝或分析方法變動的審核； 所有關(guān)鍵的偏差或違規(guī)行為及有關(guān)調(diào)查的審核； 所有不符合既定質(zhì)量標準的產(chǎn)品批號的審核； 關(guān)鍵工藝控制以及原料藥關(guān)鍵測試結(jié)果的審核；此種審核通常應(yīng)當每年進行一次，并記錄，內(nèi)容至少應(yīng)當包括：獲準的整改措施應(yīng)當及時、有效地完成。 （自檢） To verify pliance with the principles of GMP for APIs, regular internal audits should be performed in accordance with an approved schedule. 為確實符合原料藥GMP原則，應(yīng)當按照批準的計劃進行定期的內(nèi)部審計。 Internal Audits (Self Inspection) 確保驗證方案和報告的審核與批準；9. 確保進行必要的校驗，并有記錄；7. 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；5. 按照已批準的指令生產(chǎn)原料藥或者中間體；3. 生產(chǎn)作業(yè)的職責(zé)應(yīng)當以文字形式加以說明，并應(yīng)當包括，但不限于以下內(nèi)容：1. Making sure that validation protocols and reports are reviewed and approved9. Making sure that the necessary calibrations are performed and records kept7. Making sure that all production deviations are reported and evaluated and that critical deviations are investigated and the conclusions are recorded5. Producing APIs an