纯化水的检测.doc

Page:SOP#:Eff. Date:Supersedes:9/92-4001.022006.12.282006.7.1STANDARD OPERATING PROCEDURE题目：Title纯化水系统的质量监测MONITORING THE PURIFIED WATER SYSTEM起草/修订人：Author日期：Date部门主管审查：Dept. Head Approval日期：DateQA批准：Approved by QA日期：Date分 发：Distribution:QA、QC、工程QA, QC, Engineering目的：制订纯化水系统的日常质量监测及偏差处理规程，确保纯化水的质量符合要求。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.范围：适用于公司内纯化水系统（包括纯化水制备系统、纯化水使用点及取样点）的日常质量监测。在非日常监测（如验证、再验证以及要求的研究）期间，根据具体的监测方案进行；在此期间相关的日常监测暂停。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.参考文件：REFERENCE AND ATTACHMENT:SOP/题目 SOP/TITLE记录/附件/题目 FORMS/ATTACHMENTS/TITLE1-3002偏差调查附件1：纯化水系统中的使用点和取样点Deviation InvestigationsAttachment 1: Point-of-use and sampling point locations in the purified water systemF-02-014纯化水系统取样记录Purified water system sampling logbook定 义：N/ADEFINITIONS:规 程：PROCEDURE:责 任 人操 作RESPONSIBILITYACTION1.系统描述SYSTEM DESCRIPTION1.1纯化水系统由2部分组成：Purified water system consists of 2 portions:1.1.1制备系统：包括相应的设备单元和管路。Generator system：Elements include the appropriate equipment unit and the pipes.1.1.2循环管路系统：纯化水的循环分配管路。Pipe loop: Distribution loop.1.2纯化水系统中的使用点和取样点，见附件1。The point-of-use and sampling point locations in the purified water system please see Attachment 1.2.日常监测ROUTINE MONITORING2.1监测点及监测频率Monitoring points and sampling frequency2.1.1循环管路Pipe loop2.1.1.1对于有4至7天的正常工作周，每周（至少每隔23天1次）取样监测2次。如果工作周为3天或更少，则每次取样1次。如果由于停产而不使用水，日常取样可不进行。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纯化水贮罐、循环管路紫外灯后出水、总回水：每次均取样。Storage tank, sampling point after UV sterilizer in the circulating system, loop return: should be sampled each time.2.1.1.1.2其余使用点/取样点：每次从其中随机抽取一点。Other points-of-use and sampling points: one point will be sampled random each time.责 任 人操 作RESPONSIBILITYACTION2.1.2制备系统（仅供参考）Generator system (for information only)2.1.2.1每月（一般为每月的第一个工作周）取样监测1次。Collect water samples once a month (normally, the first week every month).2.1.2.1.1纯化水系统的原水（注：每年至少送卫生防疫部门检验一次）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保安过滤器出水Output water after the Safety filter2.1.2.2每2周取样监测1次。Collect water samples once per two weeks2.1.2.1.2精密过滤器出水Output water after the fine filter2.2监测项目Test items2.2.1微生物限度Microbial limit test2.2.1.1细菌、霉菌、酵母菌：“2.1”中的所有监测点Bacteria, Mildew and Microzyme: All monitoring points described in “2.1”. 2.2.1.2大肠杆菌：纯化水贮罐、总回水、精密过滤器出水，每季度检测一次。E. Coli: Storage tank, loop return and Output water after the fine filter should be tested once a quarter.2.2.2理化指标Chemical test items2.2.2.1总回水、精密过滤器出水：每2周检测一次。Loop return, Output water after fine filter will be tested once per two weeks.QC3.取样、检验SAMPLING AND TESTING3.1通则General菌检操作员3.1.1遵循取样区域的最低衣着要求，或穿洁净的化验室工作服。MicrobiologistFollow the minimum gowning requirements for the area being sampled or wear a clean lab coat.3.1.2在取水样时，应遵循无菌操作方法。Follow aseptic technique when collecting water samples.责 任 人操 作RESPONSIBILITYACTION菌检操作员3.1.3在取水样时，应肉眼检查是否有水滴泄漏，或有可见的破损。MicrobiologistWhen collecting water samples, visually inspect the water drops for leaking or visible damage.3.1.4将理化检验样品送至化验室检验；将菌检样品送至菌检室检验。Take chemistry samples to the laboratory for testing, and Send microbiology samples to microbiological laboratory for testing.3.1.4.1微生物限度检查的样品不能立即检验的，应存放于冰箱中冷藏，并于取样后24小时内完成检验。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理化检验样品的取样。Samples for Chemicals Testing. Follow these steps.3.2.1在取样前，不需用75%乙醇擦拭取样口。Do not need to sanitize the sampling port with 75% ethanol prior to collecting the water sample.3.2.2用两个洁净的500ml带盖三角瓶。Use two clean 500 ml flasks with cap.3.2.3在三角瓶上作好标记，注明日期、样品描述（如，建筑物、房间等）Label the flask with date, sample description (such as building, room, etc).3.2.4取样前，将三角瓶至少淋洗3次。Rinse the flask at least three times before collecting the sample.3.2.5取至少550ml水，以确保检验所需的足够体积。Collect at least 550 ml of water to ensure an adequate sample volume for testing.3.3微生物检验样品的取样。Samples for Microbiological Testing. Follow these steps.3.3.1使用洁净的，已灭菌的带盖250ml三角瓶或25ml试管。Use a clean, sterilized 250 ml flask or 25ml tube with closure .3.3.3在三角瓶/试管上作好标记，注明日期、样品描述（如，建筑物、房间等）Label the flask/tube with date, sample description (such as building, room, etc). 3.3.4保持样品收集三角瓶密闭直至装样。Keep the sample collection flask/tube closed until it is to be filled.3.3.5在取样前，用75%乙醇擦拭消毒取样口。Sanitize the sampling port with 75% ethanol prior to collecting the water sample.3.3.6如果是通过水系统上的软管取样的：If a sample is collected using a water system hose:责 任 人操 作RESPONSIBILITYACTION3.3.6.1当软管是附在使用点上时，用连接在上面的软管进行取样。When a hose is attached to the drop, use the attached hose to perform the sampling.3.3.6.2当没有软管连接在使用点上时，使用一洁净专用的软管。当没有软管连接在使用点上时，在同一天，同一根软管可用于同一区域中的多个使用点/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%乙醇擦拭消毒将要连接到水系统上的软管尾部。将软管连接到使用点上并可靠连接。用75%乙醇擦拭消毒软管尾部。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打开水，冲洗使用点，当使用点放出一部分水（将阀门与循环管路之间的水放净）后，取样；如取样时使用到软管，则软管应用纯化水冲洗至少3次（确保软管的内壁被彻底冲洗到）。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将水流速减小，以使装水时不泼洒（若需要）。Reduce the water flow to permit filling without splashing (if necessary).3.3.9打开取样三角瓶/试管，用无菌操作方法收集水样。Open the sample flask/tube and collect the water sample using aseptic technique.3.3.10取至少20ml水，以确保检验所需的足够体积。Collect at least 20 ml of water to ensure an adequate sample volume for testing.3.3.11在取样容器上注明取样时间。Label the sample container with the time of sampling.3.4作好取样记录。Record the sampling events in the water sampling form.责 任 人操 作RESPONSIBILITYACTION4.结果报告和评价TEST RESULTS REPORTING AND EVALUATINGQC主管或其指定人员4.1化验室主管或其指定人员对检验结果进行审核，确定数据是否超出下列的任何一项：QC Supervisor or DesigneeReview the test results and determine if data exceed any of the following:4.1.1大肠杆菌检测1个/mlE. Coli test 1 Coliform/mlQC主管或其指定人员4.1.2细菌、霉菌和酵母菌总数20CFU/ml，警戒限QC Supervisor or DesigneeTotal count of Bacteria, Mildew and Microzyme 20CFU/ml, Alert Limit4.1.2细菌、霉菌和酵母菌总数30CFU/ml，行动限Total count of Bacteria, Mildew and Microzyme 20CFU/ml, Action Limit4.1.3细菌、霉菌和酵母菌总数100CFU/ml，标准规定Total count of Bacteria, Mildew and Microzyme 100CFU/ml, Specification4.1.4理化检验结果不符合放行标准。Chemical results that do not meet release specifications4.2如果数据是可以接受的，将数据和记录送QA归档。If data are acceptable, send the completed data and records to QA for filing.QA4.3收集微生物检验数据，以季度为基础给出趋势分析。将该趋势分析抄送给菌检室和QA主管/经理。Collect data from microbiological tests. Perform trending on a quarterly basis. Forward the trending to the Microbiology Laboratory and QA Supervisor/Manager.QC4.4如果数据不可以接受，通知QA。If data are not acceptable, notify QA Management.QC4.4.1QC应将所有20CFU/ml的检验结果立即通知QA，以便于采取适当的措施（若要求）。QC 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.责 任 人操 作RESPONSIBILITYACTIONQA4.4.2针对得到的微生物检验结果，QA将根据下面的要求决定是否采取相应的措施：Given the microbial results, QA will consider any action to take in the light of the following:4.4.2.1对于任何单个点的微生物检验结果20CFU/ml，但30 CFU/ml，记录结果，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填写偏差报告，并进行偏差调查以找出最有可能的根本原因（参见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纯化水系统应用臭氧消毒后将水排空。The purified water system will be drained and sanitized by ozone.4.4.2.2.3纯化水系统重新注入纯化水，根据QA和QC菌检的要求进行取样检测。The purified water system will be refilled, sampled as specified by QA and QC Microbiology.4.4.2.2.4纯化水系统循环，但不得使用，直至菌检结果显示适于使用。The Purified water system will be circulated without use until shown to be fit for use by QC Microbiology.4.4.2.3同样，若所得的检验结果30CFU/ml，应按上面的操作执行。As such, if the microbiological results that are 30 CFU/ml, the above procedure should be followed.4.4.2.4注：对于仅用作淋洗之用的，微生物数较高的纯化水；必须经明确的证明，并表明并不给产品带来风险；该批产品必须经QA适当的评价后才能被放行。Note: Use of purified water with high microbial counts for rinsing purposes only must be clearly justified and demonstrated not to present a risk to the product and such products exposed must be appropriately as