GMP檢查之SOP純化水監(jiān)測.doc

Page:SOP#:Eff. Date:Supersedes:STANDARD OPERATING PROCEDURE題目：Title純化水系統(tǒng)的質(zhì)量監(jiān)測MONITORING THE PURIFIED WATER SYSTEM起草/修訂人：Author日期：Date部門主管審查：Dept. Head Approval日期：DateQA批準(zhǔn)：Approved by QA日期：Date分 發(fā)：Distribution:QA、QC、工程QA, QC, Engineering目的：制訂純化水系統(tǒng)的日常質(zhì)量監(jiān)測及偏差處理規(guī)程，確保純化水的質(zhì)量符合要求。PURPOSE:This document defines the procedure for routine quality monitoring and deviation disposition on purified water system to ensure the purified water quality meets the requirement.范圍：適用于公司內(nèi)純化水系統(tǒng)（包括純化水制備系統(tǒng)、純化水使用點(diǎn)及取樣點(diǎn)）的日常質(zhì)量監(jiān)測。在非日常監(jiān)測（如驗(yàn)證、再驗(yàn)證以及要求的研究）期間，根據(jù)具體的監(jiān)測方案進(jìn)行；在此期間相關(guān)的日常監(jiān)測暫停。SCOPE:This SOP is applicable to the routine monitoring on purified water system (including purified water generator system, use points and sampling points)During the non-routine monitoring period (such as validation, re-validation and special studies), the monitoring will be conducted in accordance with the specific protocol. The routine monitoring can be paused during such non-routine monitoring period.參考文件：REFERENCE AND ATTACHMENT:SOP/題目 SOP/TITLE記錄/附件/題目 FORMS/ATTACHMENTS/TITLE定 義：N/ADEFINITIONS:規(guī) 程：PROCEDURE:責(zé) 任 人操 作RESPONSIBILITYACTION1.系統(tǒng)描述SYSTEM DESCRIPTION1.1純化水系統(tǒng)由2部分組成：Purified water system consists of 2 portions:責(zé) 任 人操 作RESPONSIBILITYACTION1.1.1制備系統(tǒng)：為設(shè)備和必需的管路以制備并貯存純化水Generator system：Is the equipment and piping necessary to produce and store purified water.1.1.2循環(huán)管路系統(tǒng)：將純化水送至使用點(diǎn)并將剩余的純化水返回貯罐的分配管路。Circulating system: Is the distribution piping that delivers the purified water to the points-of-use and returns the excess to the storage tank.1.2純化水系統(tǒng)中的使用點(diǎn)和取樣點(diǎn)，見附件1。The point-of-use and sampling point locations in the purified water system please see Attachment 1.2.日常監(jiān)測ROUTINE MONITORING2.1監(jiān)測點(diǎn)及監(jiān)測頻率Monitoring points and sampling frequency2.1.1循環(huán)管路Circulating pipe system 2.1.1.1對(duì)于有4至7天的正常工作周，每周（至少每隔23天1次）取樣監(jiān)測2次。如果工作周為3天或更少，則每次取樣1次。如果由于停產(chǎn)而不使用水，日常取樣可不進(jìn)行。Collect water samples twice per week (at least once every two or three days) for normal workweeks of four to seven days. If the workweek is three days or less, collect samples once per week. If the water is not being used due to a shutdown, routine sampling may not be performed.2.1.1.1.1純化水貯罐、循環(huán)管路紫外燈后出水、總回水：每次均取樣。Storage tank, sampling point after UV sterilizer in the circulating system, loop return: should be sampled each time.2.1.1.1.2其余使用點(diǎn)/取樣點(diǎn)：每次從其中隨機(jī)抽取一點(diǎn)。Other points-of-use and sampling points: one point will be sampled random each time.2.1.2制備系統(tǒng)（僅供參考）Generator system (for information only)2.1.2.1每月（一般為每月的第一個(gè)工作周）取樣監(jiān)測1次。Collect water samples once a month (normally, the first week every month).責(zé) 任 人操 作RESPONSIBILITYACTION2.1.2.1.1純化水系統(tǒng)的原水（注：每年至少送衛(wèi)生防疫部門檢驗(yàn)一次）Source water of the generator system (note: such water sample will be sent to the local government department of hygiene and epidemic for testing annually, as a minimum.2.1.2.1.2保安過濾器出水Output water after the Safety filter2.1.2.2每2周取樣監(jiān)測1次。Collect water samples once per two weeks2.1.2.1.2二級(jí)反滲透（紫外燈后）出水Output water after RO2 (after UV sterilizer)2.2監(jiān)測項(xiàng)目Test items2.2.1微生物限度Microbial limit test2.2.1.1細(xì)菌、霉菌、酵母菌：“2.1”中的所有監(jiān)測點(diǎn)Bacteria, Mildew and Microzyme: All monitoring points described in “2.1”. 2.2.1.2大腸桿菌：純化水貯罐、總回水、二級(jí)反滲透（紫外燈后）出水，每季度檢測一次。E. Coli: Storage tank, loop return and Output water after RO2 (after UV sterilizer) should be tested once a quarter.2.2.2理化指標(biāo)Chemical test items2.2.2.1總回水、二級(jí)反滲透（紫外燈后）的出水：每2周檢測一次。Loop return, Output water after RO2 (after UV sterilizer) will be tested once per two weeks.QC3.取樣、檢驗(yàn)SAMPLING AND TESTING3.1通則General菌檢操作員3.1.1遵循取樣區(qū)域的最低衣著要求，或穿潔凈的化驗(yàn)室工作服。MicrobiologistFollow the minimum gowning requirements for the area being sampled or wear a clean lab coat.3.1.2在取水樣時(shí)，應(yīng)遵循無菌操作方法。Follow aseptic technique when collecting water samples.責(zé) 任 人操 作RESPONSIBILITYACTION菌檢操作員3.1.3在取水樣時(shí)，應(yīng)肉眼檢查是否有水滴泄漏，或有可見的破損。MicrobiologistWhen collecting water samples, visually inspect the water drops for leaking or visible damage.3.1.4將理化檢驗(yàn)樣品送至化驗(yàn)室檢驗(yàn)；將菌檢樣品送至菌檢室檢驗(yàn)。Take chemistry samples to the laboratory for testing, and Send microbiology samples to microbiological laboratory for testing.3.1.4.1微生物限度檢查的樣品不能立即檢驗(yàn)的，應(yīng)存放于冰箱中冷藏，并于取樣后24小時(shí)內(nèi)完成檢驗(yàn)。If the samples for microbiological testing cannot be tested immediately, these samples must be stored in the refrigerator and must be tested within 24 hours after sampling.3.2理化檢驗(yàn)樣品的取樣。Samples for Chemicals Testing. Follow these steps.3.2.1在取樣前，不需用75%乙醇擦拭取樣口。Do not sanitize the sampling port with 75% ethanol prior to collecting the water sample.3.2.2用兩個(gè)潔凈的500ml帶蓋三角瓶。Use two clean 500 ml flasks with cap.3.2.3在三角瓶上作好標(biāo)記，注明日期、樣品描述（如，建筑物、房間等）Label the flask with date, sample description (such as building, room, etc).3.2.4取樣前，將三角瓶至少淋洗3次。Rinse the flask at least three times before collecting the sample.3.2.5取至少550ml水，以確保檢驗(yàn)所需的足夠體積。Collect at least 550 ml of water to ensure an adequate sample volume for testing.3.3微生物檢驗(yàn)樣品的取樣。Samples for Microbiological Testing. Follow these steps.3.3.1使用潔凈的，已滅菌的帶蓋250ml三角瓶或25ml試管。Use a clean, sterilized 250 ml flask or 25ml tube with closure .3.3.3在三角瓶/試管上作好標(biāo)記，注明日期、樣品描述（如，建筑物、房間等）Label the flask/tube with date, sample description (such as building, room, etc). 3.3.4保持樣品收集三角瓶密閉直至裝樣。Keep the sample collection flask/tube closed until it is to be filled.3.3.5在取樣前，用75%乙醇擦拭消毒取樣口。Sanitize the sampling port with 75% ethanol prior to collecting the water sample.3.3.6如果是通過水系統(tǒng)上的軟管取樣的：If a sample is collected using a water system hose:責(zé) 任 人操 作RESPONSIBILITYACTION3.3.6.1當(dāng)軟管是附在使用點(diǎn)上時(shí)，用連接在上面的軟管進(jìn)行取樣。When a hose is attached to the drop, use the attached hose to perform the sampling.3.3.6.2當(dāng)沒有軟管連接在使用點(diǎn)上時(shí)，使用一潔凈專用的軟管。當(dāng)沒有軟管連接在使用點(diǎn)上時(shí)，在同一天，同一根軟管可用于同一區(qū)域中的多個(gè)使用點(diǎn)/管路。When no hose is attached to the drop, use a clean and dedicated hose. The same hose can be used for multiple drops/loops within the same area on the same day when no hose is attached to the drop. 3.3.6.3用75%乙醇擦拭消毒將要連接到水系統(tǒng)上的軟管尾部。將軟管連接到使用點(diǎn)上并可靠連接。用75%乙醇擦拭消毒軟管尾部。Sanitize the end of the hose to be attached to the water system with 75% ethanol. Attach the hose to the water drop and secure the connection. Sanitize the end of the hose with 75% ethanol.3.3.7打開水，沖洗使用點(diǎn)，當(dāng)使用點(diǎn)放出一部分水（將閥門與循環(huán)管路之間的水放凈）后，取樣；如取樣時(shí)使用到軟管，則軟管應(yīng)用純化水沖洗至少3次（確保軟管的內(nèi)壁被徹底沖洗到）。Before sampling, open the valve to flush the use of point, only a certain quantity of purified water (the water between the valve and the main distribution loop should be dropped off) has been discharged, then the purified water can sampled; if a hose is used, the hose should be flushed at least 3 times with purified water (to ensure that the inside wall has been completely rinsed).3.3.8將水流速減小，以使裝水時(shí)不潑灑（若需要）。Reduce the water flow to permit filling without splashing (if necessary).3.3.9打開取樣三角瓶/試管，用無菌操作方法收集水樣。Open the sample flask/tube and collect the water sample using aseptic technique.3.3.10取至少20ml水，以確保檢驗(yàn)所需的足夠體積。Collect at least 20 ml of water to ensure an adequate sample volume for testing.3.3.11在取樣容器上注明取樣時(shí)間。Label the sample container with the time of sampling.3.4作好取樣記錄。Record the sampling events in the water sampling form.責(zé) 任 人操 作RESPONSIBILITYACTION4.結(jié)果報(bào)告和評(píng)價(jià)TEST RESULTS REPORTING AND EVALUATINGQC主管或其指定人員4.1化驗(yàn)室主管或其指定人員對(duì)檢驗(yàn)結(jié)果進(jìn)行審核，確定數(shù)據(jù)是否超出下列的任何一項(xiàng)：QC Supervisor or DesigneeReview the test results and determine if data exceed any of the following:4.1.1大腸桿菌檢測1個(gè)/mlE. Coli test 1 Coliform/mlQC主管或其指定人員4.1.2細(xì)菌、霉菌和酵母菌總數(shù)20CFU/ml，警戒限QC Supervisor or DesigneeTotal count of Bacteria, Mildew and Microzyme 20CFU/ml, Alert Limit4.1.2細(xì)菌、霉菌和酵母菌總數(shù)30CFU/ml，行動(dòng)限Total count of Bacteria, Mildew and Microzyme 20CFU/ml, Action Limit4.1.3細(xì)菌、霉菌和酵母菌總數(shù)100CFU/ml，標(biāo)準(zhǔn)規(guī)定Total count of Bacteria, Mildew and Microzyme 100CFU/ml, Specification4.1.4理化檢驗(yàn)結(jié)果不符合放行標(biāo)準(zhǔn)。Chemical results that do not meet release specifications4.2如果數(shù)據(jù)是可以接受的，將數(shù)據(jù)和記錄送QA歸檔。If data are acceptable, send the completed data and records to QA for filing.QA4.3收集微生物檢驗(yàn)數(shù)據(jù)，以季度為基礎(chǔ)給出趨勢分析。將該趨勢分析抄送給菌檢室和QA主管/經(jīng)理。Collect data from microbiological tests. Perform trending on a quarterly basis. Forward the trending to the Microbiology Laboratory and QA Supervisor/Manager.QC4.4如果數(shù)據(jù)不可以接受，通知QA。If data are not acceptable, notify QA Management.QC4.4.1QC應(yīng)將所有20CFU/ml的檢驗(yàn)結(jié)果立即通知QA，以便于采取適當(dāng)?shù)拇胧ㄈ粢螅C will promptly inform QA of all microbiological results that are obtained that are 20 CFU/ml so that appropriate action can be taken if required.責(zé) 任 人操 作RESPONSIBILITYACTIONQA4.4.2針對(duì)得到的微生物檢驗(yàn)結(jié)果，QA將根據(jù)下面的要求決定是否采取相應(yīng)的措施：Given the microbial results, QA will consider any action to take in the light of the following:4.4.2.1對(duì)于任何單個(gè)點(diǎn)的微生物檢驗(yàn)結(jié)果20CFU/ml，但30 CFU/ml，記錄結(jié)果，不需要采取措施。For any single microbiological result that is 20 CFU/ml but 20 CFU/ml, then the use of the purified water for pharmaceutical manufacturing will stop.QA4.4.2.2.1QA填寫偏差報(bào)告，并進(jìn)行偏差調(diào)查以找出最有可能的根本原因（參見SOP 1-3002）。QA will raise a Deviation Report and the incident investigated to identify the most probable root cause (see SOP 1-3002).4.4.2.2.2純化水系統(tǒng)應(yīng)用臭氧消毒后將水排空。The purified water system will be drained and sanitized by ozone.4.4.2.2.3純化水系統(tǒng)重新注入純化水，根據(jù)QA和QC菌檢的要求進(jìn)行取樣檢測。The purified water system will be refilled, sampled as specified by QA and QC Microbiology.4.4.2.2.4純化水系統(tǒng)循環(huán)，但不得使用，直至菌檢結(jié)果顯示適于使用。The Purified water system will be circulated without use until shown to be fit for use by QC Microbiology.4.4.2.3同樣，若所得的檢驗(yàn)結(jié)果30CFU/ml，應(yīng)按上面的操作執(zhí)行。As such, if the microbiological results that are 30 CFU/ml, the above procedure should be followed.4.4.2.4注：對(duì)于僅用作淋洗之用的，微生物數(shù)較高的純化水；必須經(jīng)明確的證明，并表明并不給產(chǎn)品帶來風(fēng)險(xiǎn)；該批產(chǎn)品必須經(jīng)QA適當(dāng)?shù)脑u(píng)價(jià)后才能被放行。Note: Use of purified water with high microbial counts for rinsing purposes only must be clearly justified and demonstrated not to present a ri