纯化水制备、贮存和分配系统性能确认方案.doc

Doc# 文件编号：Page 页码：Page 1 of 59 Purified Water produce and skid纯化水制备、储存与分配系统Performance Qualification性能确认Performance Qualification Protocol性能确认方案Purified Water produce and skid纯化水制备、储存与分配系统User 用户：Hangzhou * Pharmaceutical CO., LTD. 杭州*制药有限公司Department 部门：Workshop 205205车间Location 位置：PW Station纯化水站Document NO. 文件编号：*Revision 版本号：00Doc# 文件编号：Page 页码：Page 59 of 58 Purified Water produce and skid纯化水制备、储存与分配系统Performance Qualification性能确认Review and Approval审核和批准Name名字Company公司Function职务Signature签名Date日期Written by编写 年 月 日Reviewed by审核 年 月 日Reviewed by审核 年 月 日Reviewed by审核 年 月 日Reviewed by审核 年 月 日Reviewed by审核 年 月 日Approved by批准 年 月 日Revision History版本历史Revision版本Issued date颁布日期Name of Author(s)编写人Reason for new issue颁布原因INDEX目录1.Introduction介绍41.1 Purpose目的41.2 Scope范围41.3 Responsibility职责41.4 System Description 系统描述51.5 PQ execution three stages PQ执行的三个阶段61.6 Documentation Control Specification文件管理规范71.7 List of Reference Document参考文件清单82.Test Description and Acceptance Criteria 测试描述和可接受标准92.1 Prerequisites先决条件92.2 Validation Instruments Calibration验证仪器校准92.3 SOP Check SOP检查102.4 Sterilization Verification 消毒确认112.5 Operating Parameter Verification在线测量参数确认112.6 First phase: Intensive Sampling Test第一阶段：密集取样测试132.7 Second phase: Intensive Sampling Test第二阶段：密集取样测试152.8 Third phase: Routine Sampling Test第三阶段：常规取样测试163.Personal Identification人员的鉴别174.Deviation Report偏差报告175.Comment Section注释176.List of Deviation 偏差清单187.List of Attachment附件清单188.Execution Review and Approval 回顾和批准189.Modification & Change Control 改造和更改控制1810.Index of Test Report 测试报告目录18Test Report 测试报告1 Prerequisites先决条件20Test Report 测试报告2 Validation Instruments Calibration 验证仪器校准21Test Report 测试报告3 SOP Check SOP检查22Test Report 测试报告4 Sterilization Verification 消毒确认23Test Report 测试报告5 Operational Parameter Verification 在线操作参数确认24Test Report 测试报告6 First phase: Intensive Sampling Test第一阶段：密集取样测试25Test Report 测试报告7 Second phase: Intensive Sampling Test第二阶段：密集取样测试33Test Report 测试报告8 Third phase: Routine Sampling Test第三阶段：常规取样测试41Test Report 测试报告9 Personnel Identification人员的鉴别52Test Report 测试报告10 Deviation Report偏差报告53Test Report 测试报告11 Addendum Form注释表55Test Report 测试报告12 List of Deviations偏差清单56Test Report 测试报告13 List of Attachment附件清单57Test Report 测试报告14 Execution Review and Approval 执行的审核和批准581. Introduction介绍1.1 Purpose目的The performance qualification protocol is to define the content of performance qualification protocol (PQ) of purified water produce and skid of Hangzhou * Pharmaceutical CO., LTD.本性能确认（PQ）方案描述了位于杭州*制药有限公司内新建的纯化水制备、储存与分配的性能确认方案的内容。The purpose of this protocol is to demonstrate that the purified water produce and distribution system consistently produces water that meets the requirements for Purified Water specified in the Chinese Pharmacopoeia 2010 edition, the European Pharmacopoeia (EP) 6th Edition and United States Pharmacopoeia 33 Edition. This qualification includes verification that all relevant Standard Operating Procedures used for this performance qualification are accurate and that all necessary instrumentation have been calibrated. And monitor the quality of purified water through continuous sampling.该方案用于证明该纯化水制备、储存和分配系统能持续产出符合中国药典CP 2010版、欧洲药典第六版和美国药典33版的相关规定和要求的纯化水。该确认包括确认所有用于该性能确认的相关SOP的准确性和确保所有关键设备都是经过校验的，并通过连续取样来监测纯化水的质量。1.2 Scope范围The application scope of this PQ includes the purified water produce, storage and skid system, not include loop of use points.本性能确认的范围为新建的纯化水制备、储存与分配系统,，不包括使用点分配管路。1.3 Responsibility职责On the following are defined the responsibilities relevant to PQ writing and execution.下面描述了有关PQ的编写和执行的职责。Austar responsibility*的职责： Protocol compilation方案的编写 Supply of all procedures, data, manuals, drawings and documentation necessary for the generation and execution of this protocol and the completion of the final report提供为方案编写、方案执行和报告编写所需要的所有的规程、数据、手册、图纸和文件 *.responsibility*的职责 Review and approve this protocol before execution.执行前审核和批准本方案。 Provide personnel, when necessary, to assist in the operation of equipment of equipment and system.如果需要时，提供必要的人员协助进行系统或设备的运行。 Provide personnel, when necessary, to calibrate critical and non-critical measuring, recording, and/or controlling instrumentation.如果需要时，提供必要的人员进行校准关键和非关键的测量、记录和/或控制仪表。 Define solution for non conformity.针对不一致项界定解决方法。 Protocol execution, data collection方案的实施，数据的收集 Review and approve the protocol and test reports after successful execution.审核和批准本方案和测试报告。1.4 System Description 系统描述The OSMOSTAR 15000C PWG is supplied by Shanghai Austar。该OSMOSTAR 15000C型纯化水机是由*提供。The Purified Water Generator consists of pretreatment, reverse osmosis units, EDI unit, with drinking water as raw water.该纯化水机由预处理装置、反渗透装置、EDI装置组成，采用饮用水作为源水.The purified water is stored in a 20000L storage tank. The purified water is drawn from the tank by the recycling pump, then flows to the various user points through loop and finally back to the top of the storage tank after passing through a main heat exchanger.纯化水贮存在一个20000L容量的储罐内，循环泵从储罐中取水，通过分配管路去往各个使用点，最后再通过一个主换热器回到储罐的顶部。There are fourteen loops in the distribution system.The PW quality and operation mode can be supervised by differential pressure transmitter , temperature thermometer, flowrate sensor, conductivity sensor, PH tester and TOC tester etc.该分配系统一共有14个循环回路，每个回路上均安装有压力表，流量计，电导率仪，温度传感器和公用的PH计和TOC仪。One dual function heat exchanger are installed at the return line of distribution nearby the storage tank for cooling and heating.一个双管板热交换器安装在分配系统的总回路上，并靠近储罐，用于冷却和加热。Storage and distribution system can be sanitized, via an automatic cycle, where purified water itself is the sanitizing fluid, being heated-up to 121 C through the exchangers, which be fed by plant steam.The installation has to guarantee system drain ability.储存与分配系统可以通过一个自动控制的程序进行消毒，纯化水通过热交换器(通工业蒸汽)加热至121 C。整个系统的安装被保证具有排水能力。The purified water shall conform to the requirements specified in the ChP 2005, USP 33,EP 6.1. If there are any discrepancies between different standards, the strictest standard shall be adopted. 纯化水应符合中国药典2010、美国药典33版、欧盟药典6.1版，如果有不同的标准，则选用最严格的标准。1.5 PQ execution three stages PQ执行的三个阶段Phase1: Phase 1 shall demonstrate consistent production and delivery of clean steam of the required quality. and provide data supply for operation parameters and SOP compilation and update. Phase 1consists of a test period of 5 weeks of intensive monitoring during. the full scale tests for purified water projects are performed according to the ChP 2010, the EP 6.1 and the USP 33 until the end of first phase.第一阶段：目的是证明系统能够持续产生和分配符合要求的纯化水，并为系统操作参数确定及SOP的编写或者更新提供支持。阶段包含一个连续5周的密集取样期，按照中国药典2010版、欧盟药典6.1版、美国药典33版的纯化水项目进行全项检测直到第一阶段结束。Phase 2: Phase 2 shall demonstrate consistent operation within established ranges and demonstrate consistent production and delivery of clean steam of the required quality when the system is operated in accordance with the SOPs. Phase 2 consists of test period of 5 weeks of intensive monitoring during which the system shall operate continuously without failure or performance deviation. the same test methods as those of the first phase are adopted. 第二阶段：目的是证明系统在按照相应的SOP操作后能持续生产和分配符合要求的纯化水。它包括一个连续5周的密集取样期，在此期间，系统需要持续运行而不能出现故障或性能偏差。第二阶段测试方法与第一阶段相同。The sampling plan of phase1 and phase2.第一第二阶段取样计划第一阶段 Phase1第二阶段Phase2取样日期SamplingdateEDI出水EDIoutlet储罐Tank回水点Return point送水点Outlet point取样日期SamplingdateEDI出水EDIoutlet储罐Tank回水点Return point送水点Outlet point10.31取样取样1-141-312.03取样取样1-31-1411.01取样取样1-144-612.06/4-61-1411.02取样取样1-147-912.07/7-91-1411.03取样取样1-1410-1212.08/10-121-1411.04取样取样1-1413-1412.09/13-141-1411.05取样取样1-141-312.10取样取样1-31-1411.08取样取样1-144-612.13/4-61-1411.09取样取样1-147-912.14/7-91-1411.10取样取样1-1410-1212.15/10-121-1411.11取样取样1-1413-1412.16/13-141-1411.12取样取样1-141-312.17取样取样1-31-1411.15取样取样1-144-612.20/4-61-1411.16取样取样1-147-912.21/7-91-1411.17取样取样1-1410-1212.22/10-121-1411.18取样取样1-1413-1412.23/13-141-1411.19取样取样1-141-312.24取样取样1-31-1411.22取样取样1-144-612.27/4-61-1411.23取样取样1-147-912.28/7-91-1411.24取样取样1-1410-1212.29/10-121-1411.25取样取样1-1413-1412.30/13-141-1411.26取样取样1-141-312.31取样取样1-31-1411.29取样取样1-144-601.03/4-61-1411.30取样取样1-147-901.04/7-91-1412.01取样取样1-1410-1201.05/10-121-14Phase 3: Routine monitoring of the purified water system according to the approved SOPs and SMPs for a period of time extending one year from the start of Phase , to demonstrate extended reliable performance and ensure that seasonal variations are evaluated.第三阶段：根据已批准的SOP和SMP对纯化水系统进行日常监控。测试持续一年，从而证明长期的可靠性能，确保评估季节变更的影响。1.6 Documentation Control Specification文件管理规范Below are indicated some general criteria for test data recording下面说明了一些进行记录测试数据工作的通用标准 ：l Get assurance that every document is “traceable ” that is: it has a title, system reference (for example : item number).保证每一文件是可追溯的，它应有标题，系统参考（例如项目号）。l Every annotation, recording etc., on a document must be clear, readable, dated and signed. Do not use pencils to record data, but only pen.文件中每个注解、记录等都应该清楚的、易读的、有日期和有签名的。不能使用铅笔而应使用钢笔记录数据。l For each test executed is necessary to :每次测试必须是：- Report the result, when it is applicable, in numerical form( it is not sufficient pass/fail if the result is a value).以数字化的形式记录结果（如果结果是某一数值时，PASS/FAIL是不充分的）。- Refer at the procedure used for the test if this is not described in the body format used to execute the test.如果在本次测试的格式中没有描述测试规程，注明参考的规程。- Correct each verified document (wiring diagram. P&ID, layout etc.) not corresponding to actual system, showing the as-built situation, these document will be the base for future updating.更正与实际系统不符的每一个已核实的文件（接线图 、P&ID 、布局图等），显示竣工状态，这些文件作为将来更新的基础。- Attach each print-out/attachment produced during the test execution, signing and dating it , writing a clear reference at which test the print-out/attachment refer to , if is present more than on attachment for the same test, Number progressively the attachment (page X of Y), signing and dating each attachment.附上在测试过程中所产生的打印出来的图，签名并注明日期，写清楚是哪一次测试，如果一次测试中出现多个附件，每个附件应以PAGE X OF Y 的形式清楚的表示出来，并签名和注明日期。- Sign and date each tests(signature of the people that executes and approves test must be present).每次测试应签名和注明日期（执行人和批准人的签名必须出现）。- If some test is not executed, indicate the reason why it happened, giving ,in the deviation form, a possible date for the execution. 如果有些测试没有进行，在偏差表中写明为何未执行的原因和预计执行的日期）。l Do not use covering liquids or materials on official documents, to correct errors, every writing mistake must be correct like the following example:在正式文件中不要使用修正液，修改错误必须使用以下正确的方式：System XXDD(签名)System YZ20101022 (日期年月日)Space not used must be barred, dated and signed, as indicated blow:对于不使用的部分， 必须如下面所示的划掉， 并签字和注明日期：DD20101022l Furthermore for each deviation that should occur during the execution of this PQ protocol, compile a report for non conformity/deviation management (attached to this protocol) recording:此外，在执行本方案的过程中所发生的每个偏差， 编制一个包括以下一些内容的偏差报告：- Deviation Number( progressive).偏差号。- Deviation description.偏差描述。- Activity necessary to resolve the deviation.解决偏差的必要措施。- Date of deviation resolution .Only Validation manager may decide that a deviation can be solved before or after execution.偏差解决的日期。只有验证经理可以决定偏差在进行下步确认活动之前还是之后进行解决。- Re-check results after resolution.偏差解决后的重新检查结果。1.7 List of Reference Document参考文件清单To write this protocol have been used the following reference documents:为了编写本方案， 使用了下列参考文件： (SFDA) Good Manufacturing Practice, revised in 1998(SFDA) 1998年版GMP (SFDA) Good Manufacturing Practice(Draft for comment, Dec 2009)(SFDA) GMP（2009年12月征求意见稿） EudraLex - Volume 4 Good manufacturing practice (GMP) GuidelinesEudraLex-卷4 GMP指南 China pharmacopoeia 2010 Edition中国药典 2010版 European Pharmacopoeia (EP) 6th Edition 欧洲药典（EP）第六版 United States Pharmacopeia 33 Edition美国药典33版 ISPE baseline volume4-water and steam systemISPE指南4“水和蒸汽系统”2. Test Description and Acceptance Criteria 测试描述和可接受标准2.1 Prerequisites先决条件Purpose 目的All prerequisites necessary to the PQ execution have been satisfied.所有进行性能确认的先决条件已经得到满足。Procedure程序Verify that PQ protocol has been approved and the stage of Installation and Operating Qualification has been completed with success.确认PQ方案已得到批准，IOQ 已成功完成。To ensure that the personnel involved in the protocol are all trained and are familiar with protocol.确认参与此方案的人员都已经过培训，熟悉此方案的内容。Acceptance Criteria可接受标准All the prerequisites must be satisfied before the beginning of the execution of PQ test.开始执行本测试之前，所有的先决条件必须得到满足。Test Report测试报告Fill in Test Report No.填写“测试报告”。 Recording the deviation occurred during the test execution on the deviation report.在偏差报告中记录在测试过程中所发生的偏差。2.2 Validation Instruments Calibration验证仪器校准Purpose 目的Confirm the validity of all critical instruments of the system and validation instrumentation used during the qualification.确认性能确认过程中系统和验证用关键仪器仪表的有效性。Procedure程序For each instrument used for the qualification activities identify, manufacturer, model, serial number, report their calibration and calibration due date. A copy of the calibration certificates must be attached.对系统和验证用的仪器仪表应标识出生产厂家、型号、系列号、校准日期、预计再校准日期。必须附上校准证书。Acceptance Criteria可接受标准The critical instruments are calibrated and within their calibration period, calibration certificate are available and attach to this protocol.所有关键仪器仪表已经得到校准，并在它们的校准有效期内，校准证书是可用的和附在本方案中。Test Report测试报告Fill in Test Report No.填写“测试报告”。 Recording the deviation occurred during the test execution on the deviation report.在偏差报告中记录在测试过程中所发生的偏差。2.3 SOP Check SOP检查Purpose 目的Verify the status of the SOPs for the verification of the validity and the performance of the purified water produce and skid system.确认纯化水制备储存与分配系统有效性和性能所需要的SOP文件的状态。Procedure程序Check that the SOPs needed for the performance of the purified water produce and skid system are available and they have been approved or have been drafted.检查纯化水制备储存与分配系统性能确认所需要的SOP是否都存在，并确认其处于已批准或草稿状态。Acceptance Criteria可接受标准Check that the SOPs needed for the performance of the system are available and at least available in drafts.系统性能确认所需要的SOP都存在，并且至少具备草稿格式的版本。Test Report测试报告Fill in Test Report No.填写“测试报告”。 Recording the deviation occurred during the test execution on the deviation report.在偏差报告中记录在测试过程中所发生的偏差。2.4 Sterilization Verification 清洁、消毒确认Purpose 目的Verify that the SOPs are appropriate.确认纯化水贮罐、输送管道的清洁、消毒程序是否合理，清洁、消毒频率是否适用。Procedure程序Sanitize the purified water distribution system every month.每月一次对纯化水贮管、输送管道进行消毒。Perform the Sterilization per the appropriate system SOP.按照适当的系统SOP进行消毒。Verification of the system operating parameter each.确定系统在线消毒参数。Acceptance Criteria可接受标准The quality of the purified water must be conforming to the purified water criteria specified in the various pharmacopoeias during the sterilization cycles. 在三个消毒周期内，纯化水质量必须符合各药典纯化水标准。Test Report测试报告Fill in Test Report No.填写“测试报告”。 Recording the deviation occurred during the test execution on the deviation report.在偏差报告中记录在测试过程中所发生的偏差。2.5 Operating Parameter Verification在线测量参数确认Purpose 目的To verify that the purified water system is operating within the specified parameters during the PQ.确认纯化水系统在性能确认期间在规定参数内进行操作。Procedure程序Operating parameter verification is to be performed on each sampling day during Phase and Phase testing. 操作参数的确认必须在第一阶段和第二阶段的测试中的每个取样日进行。Two times daily at least, a minimum of four hours apart, Record the values of the parameters .一天最少2次，每次间隔至少4小时。记录各个参数。Verify each of the parameters is within the specified acceptance criteria. 确认所有参数都在规定的验收标准内。 Acceptance Criteria可接受标准The actual system operating parameters must meet the specified requirements.实际系统操作参数必须达到规定要求。Purified water generator纯化水机Specifications标准Raw water flow rate FI360.3.1原水流量 FI360.3.126000L/h 10%Conductivity at 25C after RO QE270.5.1RO后产水25C电导率QE270.5.120S.cm-1PH 270.5.1at 25C after RO RO后产水PH 270.5.1812Flow after RO Unit FT270.6.1反渗透产水水流量 FT270.6.116500L/h 10%Conductivity at 25C after EDI QE270.6.1EDI后产水25C电导率QE270.6.110%Flow rate循环流速3.5m3/hConductivity of each loop 各回路电导率1S/cmTOC 总有机碳0.1MPaTest Report测试报告Fill in Test