【正文】 形成文件。除非有一套合理的系統(tǒng)允許這樣操作。No material should be released or used before a satisfactory conclusion of the evaluation by the Quality Unit, except when There must be implemented appropriate systems allowing such a practice, with the exception of intermediates for selling and active pharmaceutical inputs. 對(duì)于發(fā)生的質(zhì)量偏差，必須有通知質(zhì)量部門的程序，包括采取相關(guān)的行動(dòng)。必要時(shí)可以代理行使某些職能,但責(zé)任不能代理。t be delegated.，并在教育、經(jīng)驗(yàn)和培訓(xùn)方面有任職資格。elaboration and review of procedures and documents, including its updating。c) 衛(wèi)生 hygiene。e) 包括GMP原則應(yīng)用方面的培訓(xùn)training, including application of GMP principles。g) 合同供應(yīng)商的批準(zhǔn)和監(jiān)督 approval and monitoring of contract suppliers。i) 對(duì)文件和記錄歸檔document files and records。k) 檢查和調(diào)查可能影響中間品和藥物活性成分質(zhì)量的因素。The Quality Unit should manage all activities related to quality。b) 建立和監(jiān)督對(duì)生產(chǎn)過程中使用的原材料、中間品、包裝和標(biāo)簽材料放行或否決的制度。c) 在產(chǎn)品發(fā)貨前，對(duì)生產(chǎn)記錄和質(zhì)量控制記錄文件進(jìn)行復(fù)核。d) 證明質(zhì)量偏差已得到調(diào)查，并采取了糾正措施。e) 對(duì)于留樣的包管、儲(chǔ)存和記錄活動(dòng)進(jìn)行管理manage activities of custody, storage, and documentation of retention samples.f) 批準(zhǔn)對(duì)中間品和藥物活性成分的質(zhì)量有影響的所有程序、標(biāo)準(zhǔn)和指令。g) 批準(zhǔn)自檢計(jì)劃，并證明已經(jīng)實(shí)行。h) 批準(zhǔn)與中間品和藥物活性成分的生產(chǎn)和質(zhì)量控制有關(guān)的技術(shù)標(biāo)準(zhǔn)和第三方服務(wù)合同。i) 批準(zhǔn)對(duì)中間品和藥物成分的質(zhì)量有影響和潛在影響的變更。(j) 批準(zhǔn)驗(yàn)證主計(jì)劃、方案和報(bào)告，確保進(jìn)行必要的驗(yàn)證活動(dòng)。(k) 證明記錄和調(diào)查了與質(zhì)量有關(guān)的投訴和產(chǎn)品退回，必要時(shí)采取了糾正措施。 (l) 證明有一套有效的設(shè)備維護(hù)和校驗(yàn)體系。 m) 證明進(jìn)行了穩(wěn)定性研究，保證獲得的數(shù)據(jù)能夠證明中間品和藥物活性成分的有效期和規(guī)定的儲(chǔ)存裝運(yùn)條件。 in such a way to guarantee that obtained data supports the expiration date and the storage and shipping conditions defined for intermediates and active pharmaceutical inputs。(o) 對(duì)生產(chǎn)區(qū)的環(huán)境監(jiān)測進(jìn)行評(píng)估evaluate the environmental monitoring program of productive areas.(p) 批準(zhǔn)培訓(xùn)計(jì)劃并證明對(duì)員工進(jìn)行了最初和連續(xù)的培訓(xùn)。這些責(zé)任應(yīng)該在文件中清楚地確定下來，至少包括下列活動(dòng)：The main responsibilities of Quality Control can not be delegated. These responsibilities should be defined and documented clearly describing at least these activities: a) 制定、更新和評(píng)估 elaborate, update and review:I. 原材料、中間品、藥物活性成分、過程控制和包裝材料的標(biāo)準(zhǔn)和檢驗(yàn)方法specifications and analytical methods for raw materials, intermediates, active pharmaceutical inputs, inprocess controls and packaging materials。III. 生產(chǎn)區(qū)環(huán)境監(jiān)測程序 environmental monitoring procedures of productive areas。b) 批準(zhǔn)或否決原材料、中間品、藥物活性成分和包裝材料approve or reprove raw materials, intermediates, active pharmaceutical inputs and packaging materials。 d) 對(duì)中間品和藥物活性成分進(jìn)行穩(wěn)定性研究perform stability study analyses of intermediates and active pharmaceutical inputs。 f) 確保準(zhǔn)確標(biāo)識(shí)試劑、物料、儀器和實(shí)驗(yàn)室設(shè)備assure the correct identification of reagents, materials, instruments and lab equipments。h) 按照程序調(diào)查不合格結(jié)果 investigate results out of specification, according to procedures。j) 確認(rèn)設(shè)施和設(shè)備的維護(hù) verify the maintenance of facilities and equipments。l) 推動(dòng)對(duì)質(zhì)量控制區(qū)員工進(jìn)行最初和連續(xù)的培訓(xùn)promote initial and continuous trainings of personnel from the Quality Control area。take part of elaboration and review of standard/master formula for production of intermediates oractive pharmaceutical inputs according to written procedures。distribute production orders of intermediates or active pharmaceutical inputs according to written procedures。produce active pharmaceutical inputs and, when appropriate, intermediates according to previous approved instructions。review all the lot records and assure that they are pleted and signed。certify that all production deviations are recorded, evaluated and that critical deviations are investigated and conclusions recorded。certify that facilities and equipments are found clean, when necessary, sanitized, and duly identified。certify that the necessary calibrations are executed and records are kept。certify that protocols and validation reports are reviewed and approved。propose alterations in the process or equipment。evaluate proposed alterations for product, process or equipments。certify that facilities and equipments (when new or modified) are qualified, when necessary and。certify that maintenance of facilities and equipments are performed and records kept. 產(chǎn)品質(zhì)量評(píng)審Product Quality Review 為核實(shí)工藝的一致性，應(yīng)該定期對(duì)中間品和藥物活性成分的質(zhì)量進(jìn)行評(píng)審。 b) 評(píng)審所有不符合規(guī)定要求的批次。 c) 評(píng)審所有的關(guān)鍵偏差和相關(guān)的調(diào)查 review of all the critical deviations and related investigations。review of alterations performed in the processes or validated analytical methods。review of results from stability monitoring program。review of all the returns, plaints and recalls related to quality。review of corrective actions. 對(duì)結(jié)果進(jìn)行分析，必要時(shí),采取糾正措施并記錄、跟蹤和作出結(jié)論。自檢應(yīng)該包括：It should be elaborated a written procedure on selfinspections. The selfinspection should prise:a) 人員 personnel。c) 廠房和設(shè)備維護(hù) building and equipment maintenance。 e) 設(shè)備生產(chǎn) equipments。g) 質(zhì)量控制 Quality Control。i) 衛(wèi)生 sanitation and hygiene。k) 儀器和測量系統(tǒng)的校驗(yàn) calibration of instruments and measure systems。m) 顧客投訴 plaints。o) 廢物處理 waste management:p) 先前自檢的結(jié)果和采取的糾正措施results from early selfinspections and adopted corrective actions. 自檢小組應(yīng)該由合格的專業(yè)人員組成，對(duì)實(shí)際的操作區(qū)和GMP有很好的了解。b) 評(píng)估和結(jié)論 evaluations and conclusions。 d) 建議的糾正措施和期限，在規(guī)定的期限內(nèi)對(duì)自檢報(bào)告中的不合格項(xiàng)采取和完成糾正措施。必須有足夠數(shù)量的合格人員，通過接收指導(dǎo)培訓(xùn)和積累的經(jīng)驗(yàn)來完成、監(jiān)督和管理中間品和藥物活性成分的生產(chǎn)活動(dòng)。Establishment and maintenance of quality and manufacturing of intermediate and active pharmaceutical input depend on employees that perform them. There must be a adequate number of qualified personnel by instruction, training, and/or experience, to execute, supervise and manage manufacturing activities of intermediates and active Pharmaceutical Inputs by which the manufacturer is responsible. The individual responsibilities and authorities should be established in written procedures, prised and applied by all the involved ones. 公司應(yīng)該有組織結(jié)構(gòu)圖。員工的工作可以由別人代理完成，條件是代理的人員達(dá)到滿意的質(zhì)量水平。The pany should have an organization chart. Employees shouldn’t accumulate responsibilities in order to avoid that the quality of the intermediates and active pharmaceutical inputs is put in danger. Their attributions may be delegated to assigned substitutes as long as those present satisfactory qualification level. It can not be absence or accumulation of personnel responsibilities referring to GMP application. 所有的人員應(yīng)該了解GMP的原則并接收最初和連續(xù)的培訓(xùn)。對(duì)培訓(xùn)