1、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： 00Review and Approval审核和批准Name名字Company公司Function职务Signature签
2、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 .4Doc# 文件编号：Page 页码 ： Page 3 of 58 Puri
3、fied Water produce and skid纯化水制备、储存与分配系统Performance Qualification性能确认1.1 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 Descripti
4、on 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: Inte
5、nsive 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
6、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 Verificati
7、on 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 De
8、viation 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
9、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 produc
10、es 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
11、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
12、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
13、 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 Revi
14、ew 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
15、 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。Doc# 文件编号：Page 页码 ： Page 5 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 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
16、 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、
17、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
18、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
19、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 purifi
20、ed 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 specif
21、ied 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 delive
22、ry 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
23、 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
24、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
25、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EDIo
26、utlet储罐Tank回水点Return point送水点Outlet point10.31 取样 取样 1 -14 1 -3 12.03 取样 取样 1 -3 1 -1411.01 取样 取样 1 -14 4 -6 12.06 / / 4 -6 1 -1411.02 取样 取样 1 -14 7 -9 12.07 / / 7 -9 1 -1411.03 取样 取样 1 -14 10 -12 12.08 / / 10 -12 1 -1411.04 取样 取样 1 -14 13 -14 12.09 / / 13 -14 1 -1411.05 取样 取样 1 -14 1 -3 12.10 取样 取样
27、 1 -3 1 -1411.08 取样 取样 1 -14 4 -6 12.13 / / 4 -6 1 -1411.09 取样 取样 1 -14 7 -9 12.14 / / 7 -9 1 -1411.10 取样 取样 1 -14 10 -12 12.15 / / 10 -12 1 -1411.11 取样 取样 1 -14 13 -14 12.16 / / 13 -14 1 -1411.12 取样 取样 1 -14 1 -3 12.17 取样 取样 1 -3 1 -1411.15 取样 取样 1 -14 4 -6 12.20 / / 4 -6 1 -1411.16 取样 取样 1 -14 7 -
28、9 12.21 / / 7 -9 1 -1411.17 取样 取样 1 -14 10 -12 12.22 / / 10 -12 1 -1411.18 取样 取样 1 -14 13 -14 12.23 / / 13 -14 1 -1411.19 取样 取样 1 -14 1 -3 12.24 取样 取样 1 -3 1 -1411.22 取样 取样 1 -14 4 -6 12.27 / / 4 -6 1 -1411.23 取样 取样 1 -14 7 -9 12.28 / / 7 -9 1 -1411.24 取样 取样 1 -14 10 -12 12.29 / / 10 -12 1 -1411.25
29、取样 取样 1 -14 13 -14 12.30 / / 13 -14 1 -1411.26 取样 取样 1 -14 1 -3 12.31 取样 取样 1 -3 1 -1411.29 取样 取样 1 -14 4 -6 01.03 / / 4 -6 1 -1411.30 取样 取样 1 -14 7 -9 01.04 / / 7 -9 1 -1412.01 取样 取样 1 -14 10 -12 01.05 / / 10 -12 1 -14Phase 3: Routine monitoring of the purified water system according to the approve
30、d SOPs and SMPs for a period of time extending one year from the start of Phase , to demonstrate extended reliable Doc# 文件编号：Page 页码 ： Page 7 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performance and ensure that seasonal variations are evaluated.第三阶段：根据已批准的 SOP 和
31、 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 ： Get assurance that every document is “traceable ” that is: it has a title, system reference (for example : item nu
32、mber).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）。 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。 For each test executed is necessary to :每次测试必须是：- Report the result, wh
33、en 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
34、 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, sig
35、ning 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 P
36、AGE 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
37、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）。 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 XX DD(签签 名名 )System YZ (日期年月日日期年月日 )Space not used must be barred, dated and sign
38、ed, 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： 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 Numbe
39、r( 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 reso
40、lution.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
41、 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”
42、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.DDDoc# 文件编号：Page 页码 ： Page 9 of 58 Purified Water produce and skid纯化水制备、储存与分配系统Performance Qualification性能确认所有进行性能确认的先决条件已经得到满足。Procedure 程序Verify
43、 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
44、 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.1填写“ 测试报 告1.” 。 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 Instrum
45、ents 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, r
46、eport 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 an
47、d 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.2填写“ 测试报 告2.” 。 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 ve
48、rification 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
49、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.3填写“ 测试报 告3.” 。 Recording the deviation occurred during the test executio
