TOC验证方案和报告.docx

EXECUTION APPROVAL SIGNATURES
批准执行签名

The signatures below indicate approval of this protocol and its attachments and indicate that it is ready for execution. Any changes or modifications to the intent or the acceptance criteria of this protocol, following approval, requires the generation of an amendment which must be approved prior to execution.
下面的签名表示批准本文件及其附件，且表明已经为执行作好了准备。在批准后，对本文件的目的或验收标准进行的任何改变或修正都必须起改善的作用，在执行以前就必须取得批准。

***Company LTD: Date

***: Date

***: Date

1.0 SCOPE: 范围 4
2.0 PURPOSE: 范围 4
3.0 BACKGROUND: 背景 4
4.0 INTRODUCTION: 介绍 4
5.0 REFERENCES: 参考书目 5
6.0 RESPONSIBLE PARTIES AND RESPONSIBILITIES: 责任方及其责任 7
7.0 SYSTEM DESCRIPTION: 系统说明 9
8.0 TESTING PROCEDURES: 测试程序 10
9.0 ACCEPTANCE CRITERIA: 验收标准: 11
Attachment 1 - Validation Test Equipment and Materials附件1—确认测试设备和材料 13
Attachment 2 - Specification and Purchase Order Verification附件2—规范和采购单确认 14
Attachment 3 - Engineering Drawing List附件3—工程图纸清单 15
Attachment 4 - Standard Operating Procedures List附件4—标准操作程序清单 16
Attachment 5 - Preventive Maintenance附件5—预防性维护 17
Attachment 6 - Operation and Maintenance Manual List附件6—操作和维护手册清单 18
Attachment 7 - Major Component Labeling List附件7—主要部件标签清单 19
Attachment 8 - Critical Instrument List附件8—关键仪器清单 20
Attachment 9 - Non-Critical Instrument List附件9—非关键仪器清单 21
Attachment 10 - Spare Parts List附件10—备件清单 22
Attachment 11 - Utility Data Sheet: Electrical附件11—公用工程数据表：电 23
Attachment 12 - Utility Data Sheet: Compressed Air附件12—公用工程数据表：压缩空气 20
Attachment 13 - Operational Testing, TOC Analyzer附件13—操作测试，TOC分析器 241
Attachment 14 - ROM and Configuration Test附件14—ROM和构造测试 262
Attachment 15 - Mechanical Check Test附件15—机械检查测试 29
Attachment 16 - Flow Test附件16—流量测试 31
Attachment 17 - Linearity/ Sample Measurement Test附件17—线性/样品测量测试 33
Attachment 18 - Operational Testing, TOC AutoSampler附件18—操作测试，TOC自动取样 30
Attachment 19 - Mechanical Test附件19—机械测试 41
Attachment 20 - Sample Test附件20—样品测试 43
Attachment 21 - Sparge Test附件21—喷射测试 44
Attachment 22 - Magnetic Stirrer Test附件22—磁力搅拌器测试 45
Attachment 23 - Signature Verification List附件23—签名确认清单 36
Attachment 24 - Protocol Deviation Log附件24—文件偏差日志 37
Attachment 25 - Protocol Deviation Record附件25—文件偏差记录 38
Attachment 26 - Protocol Execution Approval Signature Data Sheet附件26—文件执行批准签名数据表 39
1.0 SCOPE:
范围

This Installation/Operational Qualification (IOQ) study will be performed on the Total Organic Carbon Analyzer (TOC) located in ***.
本安装/操作确认（IOQ）文件应用于位于***的总有机碳分析器(TOC)。

This protocol describes the equipment, test procedures, specifications, documents, and references used to establish that the TOC has been installed and operates in accordance with the manufacturer’s design specifications, and those of *** Company, LTD. The facility will be referred to as *** through out the remainder of this document. The unit will be referred to as the “TOC” throughout this document.
本文件内容涉及设备、测试步骤、规格、文档和参考书目，这些是用来确保TOC已经按生产商设计规范和***公司要求安装和操作。本文件下文中工厂指的是***，单元指的是“TOC”。

All firmware that is qualified, as part of this protocol, shall be identified as to version or other unique characteristic during Installation Qualification and a Firmware Letter of Assurance included in the documentation. Hardware or firmware associated with the instrument or system shall be under configuration control with change control procedures in place.
作为本文件的一部分，在安装确认和文件中的固件质保书中，固件的版本和其他唯一的标识号都必须识别。与仪器或系统有关的硬件或固件都有结构控制，且有在线变化控制。

Functional testing of the integrated system will be performed to ensure system integrity where necessary.
如果需要，可对整个系统进行功能性测试，确认系统的完整性。
2.0 PURPOSE:
目的

The execution of this protocol will demonstrate and document that the TOC has been installed and operates according to the manufacturer's specifications and *** requirements.
本文件的执行将记录和证明TOC已经按生产商规范和***要求安装和操作。
3.0 BACKGROUND:
背景

The TOC is a new piece of equipment purchased specifically for use at ***.
TOC是为***使用而特别采购的一套新设备。

4.0 INTRODUCTION:
介绍

Installation checks will be performed to verify and document that the equipment is installed with the proper supporting utilities, services, and components. All instrument calibration, standardization, or adjustment will be performed and documented for the measuring equipment used during the execution of this protocol. Standards used will be traceable to the National Institute of Standards and Technology (NIST). Other accepted standards will be used where applicable if NIST standards do not exist.
进行安装检查，以确认和记录设备已经与相关的公用工程、服务和部件连接。在文件执行过程中，作为测量工具，所有的仪器校验、标准化或调整都将进行，且记录下来。所使用的标准都可追溯到美国国家标准和技术研究院(NIST)。如果NIST不涉及的地方也可使用其他的验收标准。

Documentation associated with the TOC, such as operator’s or owner’s manuals, system drawings, purchase specifications, cut sheets, component specification sheets, material listings, installation diagrams, component plans, and other data, etc., may be reviewed in this report. Copies of these will be included in this report or the storage location of the documentation will be recorded.
在本报告中审核与TOC有关的文件，如操作者或所有者手册、系统图纸、采购要求、部件规范表、材料清单、安装图纸、平面布局图和其他的数据，等等。该报告包括有他们的复印件，或记录了文档储存地点。

Operational checks will be performed to verify and document that the TOC is operating in accordance with the manufacturer's specifications and *** requirements.
进行操作检查，确认和记录TOC的操作符合生产商规范和***要求。

Any deviations from the protocol or from specifications or any exceptional conditions encountered will be documented and identified for review on the Protocol Deviation Report Form. The deviations and exceptional conditions noted will be investigated and appropriate actions determined and implemented. The investigations, along with the corrective actions and their justifications, will be documented on the Protocol Deviation Report Form.
任何与文件或规范的偏差或遇到任何例外的情况都要记录下来，加以鉴别，以供文件偏差报告表的审查。记录的偏差和例外情况要进行调查，而且决定并采取相应的措施。文件偏差报告表中需记录有调查、纠正性措施及其理由。

Final protocol package approval will be by the same personnel who initially approved the protocol, by their designee, or by another person holding an equivalent level of authority.
最终文件包的批准人必须是文件最初批准人、其指定人、或其他的有同等权力的人员。

5.0 REFERENCES:
参考书目

This protocol conforms to the applicable guidelines of the publications listed below. Each publication shall be the latest revision with all addenda in effect on the date of approval of the protocol, unless otherwise noted.
该文件符合下列出版物中的规范。除非另外注明，否则每个出版物都指的是截止批准之日的最新的版本，其附录也有效。

· 21 CFR Parts 210 and 211: Code of Federal Regulations; Current Good Manufacturing Practice for Finished Pharmaceuticals
21 CFR 第 210和211部分：联邦条例法典，成品药cGMP

· USP 24 – United States Pharmacopeia
USP 24，美国药典

· SOP CZ-50-0019, Operation of TOC Analyzer
SOP CZ-50-0019, TOC分析器操作

· NIST – National Institute of Standards and Technology
NIST –美国国家标准技术研究所

6.0 RESPONSIBLE PARTIES AND RESPONSIBILITIES:
责任方及其责任

*** Company
***公司

· Execution of Qualification packages.
执行确认文件包
· Generation of Final Report.
准备最终报告
· Review and approval of the original protocol.
审核和批准原始文件
· Review and approval of the completed protocol package and the final report.
审核和批准完成的文件包和最终报告

*** Engineering / Maintenance Responsibilities:
*** 工程/维护责任：

· Supply support and technical expertise needed in the preparation and execution of the protocol.
准备和执行文件时提供支持和技术意见
· Supply all documents, data, procedures, manuals, and drawings needed to generate and execute the protocol and complete the final report.
提供编写和执行本文件时所需要的所有文件、数据、程序、手册和图纸，完成最终报告

***

· Oversee the validation process.
监督验证程序
· Supply support needed in the preparation and execution of the protocol.
准备和执行文件时提供支持
· Review and approval of the original protocol.
审核和批准原始文件
· Review and approval of the completed protocol package and the final report.
审核和批准完成的文件包和最终报告

***

· Oversee the validation process.
监督验证程序
· Supply all procedures, data, manuals, drawings, and documentation needed to generate and execute the protocol and complete the final report.
提供文件编写和执行时所需的所有程序、数据、手册、图纸和文件，完成最终报告
· Supply testing and assay support for the execution of this protocol.
执行文件时提供测试和分析支持
· Supply support and technical expertise needed in the preparation and execution of the protocol.
准备和执行文件时提供支持和技术意见
· Review and approval of the original protocol.
审核和批准原始文件
· Review and approval of the completed protocol package and the final report.
审核和批准完成的文件包和最终报告

7.0 SYSTEM DESCRIPTION:
系统说明

The Shimadzu TOC-VCSH consists of a standalone TOC-V Combustion Analyzer, high sensitivity, an ASI-V autosampler which uses up to 68 of the 40 mL vials and has septum-piercing capability, and a Pure Air Generator which will deliver up to 1200 mL/min of air at the level necessary for the TOC -VCSH (TOC 5000) to perform ultra-low level analyses. The system is not a PC control one, it utilizes a built-in firmware, which has a LCD display, keyboard and printer. Also included is a magnetic stirrer to mix the contents of the 40-mL vials, if desired for samples with high particulate matter, for example. The TOC-VCSH is designed and configured to analyze a variety of water sample types, including pharmaceutical water, drinking water, wastewater, and saline (salt) water.
Shimadzu TOC-VCSH有一个独立的TOC-V燃烧分析器、高灵敏度、一个使用最多68个40 mL烧瓶、有 隔膜穿刺功能的ASI-V自动取样器、和一个洁净空气发生器，该发生器能传输最多1200 mL/分空气，空气级别是TOC -VCSH (TOC 5000)进行超低水平分析所需要的等级。该系统不是由PC控制，而是由带LCD显示器、键盘和打印机的嵌入式固件。它还包括一个磁力搅拌器，混合40-mL小瓶中盛放的物质，如果需要得到如高微粒样品，则可以使用该搅拌器。TOC-VCSH的设计和构造是为了分析多种水样类型，包括制药用水、饮用水、废水和盐水。

The TOC-VCSH utilizes the approved Platinum catalyst and 680oC combustion technique to oxidize aqueous samples. The combustion type TOC eliminates salt interferences and ensures complete oxidation even with high molecular weight compounds and suspended particles. The Non-Dispersive Infrared (NDIR) Detector provides for maximum sensitivity and durability. The measuring range is from 4 micrograms/ liter (ppb) to 25,000 milligrams/ liter (ppm).
TOC-VCSH利用合格的铂催化剂和680oC燃烧技术来氧化水样。燃烧类的TOC排除了盐的干扰，确保了即使有高分子量化合物和悬浮颗粒也能完全氧化。无弥散红外线(NDIR)探测器能保证最大的灵敏度和耐久度。其测量范围是4微克/升(ppb)到25,000毫克/升(ppm)。

The microliter syringe and a slide-type flow switching valve are used for the high precision sample injection system. The precision or Coefficient of Variation (CV) is less than 1.5% for replicate injections. Average analysis time is approximately 3 minutes each for Total Carbon (TC) and Inorganic Carbon (IC) methods. An internal feature allows auto-dilution of samples 2-50 times, if desired. The auto-diluter permits the user to be able to create a 10-point calibration curve from one standard.
高精度取样注射系统采用微升注射器和滑动型流量开关阀。重复注射精度或变化系数(CV)低于1.5%。总碳(TC)和无机碳(IC)方法每种平均分析时间是约3分钟。如果需要，其内部可以自动稀释样品2-50次。操作者可以用自动稀释器编制一种标准的10点校验曲线。

The TC Measurement is made by passing Carrier Gas (purified air from the Balston Generator) at a controlled flow rate of 150 mL/ min through an oxidation catalyst-filled TC combustion tube, heated to 680 oC. When the sample pretreatment/ injection system injects the sample into the combustion tube, the TC in the sample is oxidized or decomposes to create carbon dioxide. The carrier gas carrying the combustion products from the combustion tube is cooled and dehumidified in the dehumidifier before passing via the halogen scrubber into the sample cell of the non-dispersive infrared detector (NDIR), where the carbon dioxide is detected. The NDIR analog signal forms a peak, and the data processor calculates the peak area.
TC测量的方法是使载气（Balston发生器里出来的洁净气体）以150 mL/分的速度通过装有氧化催化剂、加热到680 oC的TC燃烧管。当样品的前处理/注射系统将样品注射进燃烧管时，样品中的TC被氧化或分解，生成二氧化碳。载气从燃烧管中出来，携带燃烧产物，先在减湿器中冷却且减湿，然后通过卤素洗涤器进入无弥散红外线(NDIR)探测器样品室，在此处探测二氧化碳。NDIR模拟信号产生一个高峰，数据处理器将计算其峰值。

To measure the TC concentration of the sample, the relationship between the TC concentration and peak area (calibration curve) is predetermined using a TC standard solution, to express the peak area as a ratio of the TC concentration. TC (Total Carbon) = IC (Inorganic Carbon) + TOC (Total Organic Carbon)
为了测量样品的TC浓度，TC浓度和峰值（校验曲线）之间的关系必须用TC标准溶液先确定，说明峰值随TC浓度比率的变化情况。TC (总碳) = IC (无机碳) + TOC (总有机碳)

The IC Measurement is made by sparging an acidified sample with the carrier gas (purified air) to convert only the IC in the sample to carbon dioxide. This carbon dioxide is detected by the NDIR and the sample IC concentration is measured in the same way as TC. The IC is a combination of carbonate and bicarbonate.
IC测量方法是将酸化样品喷射到载气(洁净气体)中，只将样品中的无机碳转化成二氧化碳。NDIR探测该二氧化碳，样品IC浓度的测量方法则和TC一样。IC是碳酸盐和重碳酸盐的混合物。

The TOC Measurement is actually a calculation: TOC = TC - IC.
TOC的测量其实只是一个计算：TOC = TC - IC

8.0 TESTING PROCEDURES:
测试程序

The installation/operational qualification will be performed using the protocol attachments. All pertinent information will be recorded on these forms. Copies of the forms may be obtained from QA. Document results and data concurrently with the execution of this protocol. Mark through any unused spaces with a single line and initial and date. Mark spaces that do not apply to the system being qualified with Not Applicable (N/A) and provide an explanation where appropriate. Document any deviations or abnormalities observed during the execution of the protocol.
借助文件附件进行安装/操作确认。把所有有关信息记录在这些表格中。必要时也可向QA索取表格。执行文件的同时记录结果和数据。未使用的地方用单线划去，签名，并注明日期。用不适用（N/A）标明不适用系统的地方，并且在合适的地方写明理由。记录下执行文件时发现的任何偏差或不正常的情况。

NOTE: Any exceptions to this protocol must be fully investigated and documented. This IOQ can be considered acceptable with exceptional data only if the cause of the exception has been determined or an assignable cause can be attributed to it and it can be proven that such data will not invalidate the protocol studies. Quality Assurance is responsible for determining the acceptability of any exceptional data.
备注：对本文件中的任何例外进行完全调查和记录。只有当例外的原因已经确定，或可以归结为特定的原因，且能证明该数据不会使文件无效时，这个有例外数据的IOQ才可以接受，QA有权决定是否接受例外数据。

9.0 ACCEPTANCE CRITERIA:
验收标准

· Test Equipment and Materials - All test equipment used during protocol execution must be documented. If the test equipment is not calibrated, a reason must be recorded and justified.
检验设备和材料- 文件执行过程中的所有检验设备都必须有记录。如果检验设备没有校验，必须写明并说明理由。

· Specifications and Purchase Orders - All associated specifications and purchase orders with this equipment will be attached.
规范和采购单 — 所有与该设备有关的采购单都在文件附件中。

· Drawings and P&IDs - All drawings must be current or redlined markups of the most current drawings.
图纸和P&ID图—所有的图纸必须都是最新的或用红线标注的最近图纸

· Standard Operational Procedures - All Standard Operational Procedures will be in a draft format. Draft SOPs will be maintained in the History File.
标准操作程序 – 所有的标准操作程序都是图表的形式。SOP程序保存在历史文件中。

· Preventive Maintenance – Draft Preventive maintenance procedure must be available for the system and its associated pieces of equipment in a draft format. Draft Preventive Maintenance Procedures will be maintained in the History File.
预防性维护 –系统和相关设备的零件都必须有预防性维护程序。预防性维护程序保存在历史文件中。

· Operational and Maintenance Manual - List all