译文选自《Julia法规翻译》，官网原文点击”阅读原文“下载

WHO 工作文件 QAS/19.791

GOOD CHROMOTOGRAPHY PRACTICES

优良色谱规范

(February2019)

DRAFT FOR COMMENTS

征求意见稿

Description of Activity 活动描述	Date 日期
Following a recommendation by the WHO Expert Committee on Specifications for Pharmaceutical  Preparations (ECSPP) byDr André Van Zyl, a member of the ECSPP, the WHO Secretariat was recommended to develop  a new guidance ongood chromatography practices.	October 2018
WHO制剂标准专家委员会（ECSPP）建议，ECSPP成员Dr André Van Zyl建议WHO秘书处起草优良色谱规范指南	2018年10月
Preparation of first draft working document.	December  2018 -February 2019
第一份工作文件草案起草	2018年12月-2019年2月
Mailing of working document to theExpert Advisory Panelon the International Pharmacopoeiaand Pharmaceutical Preparations  (EAP) inviting comments and posting of the working document on the WHO website for public consultation.	February–  May 2019
将文件草案发给国际药典和药品专家顾问团(EAP)征求意见，在WHO官网上发布征求公众意见	2019年2-5月
Consolidation of comments receivedand review of feedbacks.Preparation of working document for discussion.	June2019
整合收到的意见和反馈审核。起草工作供讨论。	2019年6月
Discussion of working document and feedbacks  received duringthe informal Consultation on Good Practices  for Health Products  Manufacture and Inspection.	July2019
讨论工作文件和优良药品生产与检查规范非正式咨询期间收到的反馈	2019年7月
Revision of the working document  based on comments received  during the informal Consultation on Good Practices forHealth Products  Manufacture and Inspection.	End ofJuly2019
根据优良药品生产与检查规范非正式咨询期间收到的建议修订工作文件	2019年7月底
Mailing of revised working documentto the  EAP inviting comments and posting the working document  on the WHO website for public consultation.	August – September 2019
将修订后的工作文件发给EAP征求意见，在WHO官网上发布工作文件征求公众意见	2019年8-9月
Consolidation of comments receivedand review of feedbacks.Preparation of working document for discussion.	End of September 2019
整合所收到的建议，审核反馈意见。起草工作文件供讨论	2019年9月
Presentation to the Fifty-fourth meeting of the ECSPP.	14 -18 October2019
提交第54次ECSPP会议	2019年10月14-18
Any other  follow-up action as required.
其它所需后续措施

1.      INTRODUCTION AND SCOPE 介绍与范围

The use of chromatography methods (such as High Pressure Liquid Chromatography (HPLC) and Gas Chromatography (GC)) in quality control laboratory analysis has increased significantly in recent years.

近年来色谱方法（如高压液相色谱（HPLC）和气相色谱（GC））的使用在QC实验室分析中已有显著增加。

HPLC and GC methods are used in, for example, the identification of materials and products, for determination of assay and related substances in materials and products, as well as in validation such as process validation and cleaning validation.

HPLC和GC方法被用于，例如，物料和产品鉴别、物料和产品中含量和有关物质检测，以及验证如工艺验证和清洁验证。

Due to the criticality of the results obtained through chromatography, manufacturers should ensure that the data acquired is accurate and reliable. Results should meet ALCOA+ principles (i.e. attributable, legible, contemporaneous, original and accurate).

由于通过色谱获得的结果非常关键，生产商应确保所获取的数据的准确性和可靠性。结果应符合ALCOA+原则（即可追溯、清晰、同步、原始和准确）。

This guideline provides information on good practices to be considered in the analysis of samples when chromatographic systems are used. The principles should be applied in the analysis of, for example, raw materials, starting materials, intermediates, in-process materials and finished products.

本指南提供了在使用色谱系统进行样品分析时需要考虑的优良规范。在分析如原料、起始物料、中间体、中控物料和成品中应使用这些原则。

The principles contained in this guideline are applicable to all types of chromatographic analysis  used in, for example, assay determination, testing for related substances and impurities, process validation, cleaning validation, cleaning verification and stability testing.

本指南中人原则适用于如含量检测、有关物质和杂质检测、工艺验证、清洁验证、清洁确认和稳定性测试中所用的所有类型色谱分析。

2.      GLOSSARY 术语解释

ALCOA

A commonly usedacronym for “attributable, legible, contemporaneous, original and accurate”.

常用术语，代表“可追溯、清晰、同步、原始和准确”。

ALCOA+

A commonly used acronym for “attributable, legible, contemporaneous, original and accurate” which puts additional emphasis on the attributes of being complete, consistent, enduring and available – implicit basic ALCOA principles.

常用术语，代表“可追溯、清晰、同步、原始和准确”，以及在其上增加ALCOA基本原则的更多属性，即完整、一致、持久和可及性。

Backup 备份

A backup means a copy of one or more electronic files created as an alternative in case the original data or system are lost or become unusable (for example, in the event of a system crash or corruption of a disk). It is important to note that backup differs from archival in that backup copies of electronic records are typically only temporarily stored for the purposes of disaster recovery and may be periodically overwritten. Such temporary backup copies should not be relied upon as an archival mechanism.

备份指创建一份或多份电子文件，在原始数据或系统丢失或不可使用时（如系统崩溃或磁盘损坏）作为替代用途。注意备份与归档是不一样的，电子记录备份一般只是临时存贮用于灾难恢复，可能会定期覆盖。不应依赖此种临时备份件作为归档用途。

Calibration 校正

The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established.

在指定条件下建立仪器或系统测量指示值（尤其是称重值）、记录和控制，或物料测量代表值，与对应的一个标准物质已知值之间的关系的一系列操作。应建立测量结果的可接受限度。

Chromatographic column 色谱柱

A tube commonlyfilled with a stationary phase over which a sample and mobile phase move, used in chromatographic analysis.

一支通常用固定相填充，样品和流动相在其中移动，用于色谱分析的柱子。

Data 数据

All original records and true copies of original records, including source data and metadata and all subsequent transformations and reports of these data, which are generated or recorded at the time of the GMP activity and allow full and complete reconstruction and evaluation of the GMP activity. Data should be accurately recorded by permanent means at the time of the activity. Data may be contained in paper records (such as worksheets and logbooks), electronic records and audit trails, photographs, microfilm or microfiche, audio- or video-files, or any other media whereby information related to GMP activities is recorded.

所有原始记录和原始记录的真实副本，包括源数据和元数据以及这些数据的所有后续转移及报告。这些数据是在GMP活动时生成或记录，可全面完整重构及评估该GMP活动。数据应在活动发生时采用永久方法准确记录。数据可保存在纸质记录上（例如工作记录和日志）、电子记录上和审计追踪上、图片上、微缩胶卷上、影音文件或任何其它记录与GMP活动有关信息的媒介上。

Exponential skim 指数撇除

The creation of a curvature in the skim line in an attempt to approximate the underlying baseline of the parent peak.

在撇去线上创建一个曲率以使其接近母峰的下基线。

Exponential curve fitting 指数曲线设置

The drawing of acurve using an exponential equation through the start and end of the child peak. The curve passes under each child peak that follows the parent peak; the area under the skim curve is subtracted from the child peaks and added to the parent peak.

使用指数方程画一条通过子峰起点和结点的曲线。该曲线通过母峰后的所有子峰，将撇去曲线下的面积从子峰面积中扣除，加和到母峰面积上。

Front peak skim 前伸峰撇去

The process of integrating child peaks on the front (upslope) of a peak subject to specified criteria.

根据指定标准对一个峰的前沿部分（上斜部分）上的子峰进行积分的过程

Integration 积分

The process of applying specified parameters for chromatographic peaks (determination of height, area and retention time).

采用指定参数对色谱峰进行处理（确定峰高、峰面积和保留时间）

Metadata 元数据

Metadata is data about data that provides the contextual information required to understand those data. These include structural and descriptive metadata. Such data describe the structure, data elements, interrelationships and other characteristics of data. They also permit data to be attributable to an individual. Metadata necessary to evaluate the meaning of data should be securely linked to the data and subject to adequate review. For example, in weighing, the number 8 is meaningless without metadata, such as, the unit, milligram, etc. Other examples of metadata include the time/date stamp of anactivity, the operator identification (ID) of the person who performed an activity, the instrument ID used, processing parameters, sequence files, audit trails and other data required to understand data and reconstruct activities.

元数据是提供理解数据所需环境信息的数据。其中包括结构性和描述性元数据。此类数据描述结构、数据元素、相互关系和数据的其它特性。他们亦可让数据追溯至个人。评估数据含义所需的元数据应与数据安全链接，并进行充分审核。例如，在称重过程中，如果没有元数据，如单位mg等，数字8是无意义的。元数据的其它例子包括一个活动的时间/日期戳，执行活动的操作员身份（ID）、所用仪器ID、处理参数、序列文件、审计追踪和理解数据和重构活动所需的其它数据。

Peak valley ratio 峰谷比

The peak to valley ratio is a measure of quality indicating how well the peak is separated from other substance peaks.

峰谷比是显示一个峰与其它物质峰分离程度的质量指标

Qualification 确认

Documented evidence that premises, systems or equipment are able to achieve the predetermined specifications properly installed, and/or work correctly, and lead to the expected results.

证明设施、系统或设备能够达到预定标准、适当安装，和/或正确运转并获得预期结果的文件化证据。

Rear peak skim 峰尾撇去

The process of integrating child peaks on the tail (downslope) of a peak subject to specified criteria.

根据指定标准对一个峰的拖尾部分（下斜部分）上的子峰进行积分的过程

Restoration 恢复

The process of retrieving electronic data that had previously been backed-up and presented in a readable format.

恢复之前已有备份的电子数据并以可读格式展现的过程。

Source data 源数据

Original data obtained as the first-capture of information, whether recorded on paper or electronically.

在信息首次捕获中获取的纸质或电子原始数据。

Straight line skim 直线撇去

The process ofdrawing a straight line through the start and end of a child peak. The height of the start of the child peak is corrected for the parent peak slope. The area under the straight line is subtracted from the child peak and added to the parent peak.

画一条通过子峰起点和终点的处理方法。子峰的起点高度根据母峰斜率进行调整。直线下面的面积从子峰面积中扣除，加到母峰面积上。

Tangential skim 切线撇去

The process of integrating a small peak located on the tailing edge of a larger peak. The baseline of the small peak becomes a tangent drawn from the valley of the larger peak to the tangent point on the chromatogram.

对一个较大峰的尾部边缘上一个小峰进行积分的过程。小峰的基线成为大峰峰谷至色谱图切点的一条切线。

Validation 验证

Action of proving and documenting that any process, procedure or method actually and consistently leads to the expected results.

提供和记录所有工艺、程序或方法实际一致获得预期结果的行动。

Valley height ratio 峰高比

Valley height ratio is the ratio of the height of the child peak above the baseline to the height of the valley above the baseline. This ratio must be smaller than the specified value for the child peak to be skimmed.

峰高比是高于基线的子峰峰高比高于基线的谷高比值。该比率必须小于要撇去的子峰的指定值。

3.      CHROMATOGRAPHIC SYSTEMS 色谱系统

3.1.   Manufacturers should select, install and use chromatographic systems that are appropriate for the intended use.

生产商应选择、安装和使用适合其既定用途的色谱系统。

3.2.   Vendor qualification should ensure that hardware and software are suitable for their intended application and that after-sales services will be available.

供应商确认应确保硬件和软件适合其既定应用程序，能提供售后服务。

3.3.   Valid agreements should specify the respective responsibilities between the purchaser and supplier.

购买方和供应商之前应有有效协议说明双方职责。

3.4.   Systems should meet regulatory requirements and expectations for Good Manufacturing Practices, including but not limited to, ensuring that data are acquired, processed and stored in accordance with national legislation and ALCOA+ principles.

系统应符合法规要求和GMP要求，包括但不仅限于，确保数据采集、处理和存贮符合国家法律和ALCOA+原则。

4.      QUALIFICATION AND VALIDATION 确认与验证

4.1.   The scope and the extent of validation and qualification of chromatographic systems should be determined based on risk management principles.

色谱系统验证和确认的范围和程度应根据风险管理原则确定。

4.2.   The approach to, and execution of validationand qualification, should be described in an authorized document such as avalidation master plan.

验证和确认方法及其执行应在批准的文件如验证主计划中阐明。

4.3.   All stages of qualification should be considered and may include, for example, user requirement specifications (URS), design qualification (DQ), factory acceptance test (FAT), site acceptance test(SAT), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).  (See also the Guideline for Computerized Systems).

确认的所有阶段均应考虑包括如用户需求手册（URS）、设计确认（DQ）、工厂接收测试（FAT）、用户接收测试（SAT）、安装确认（IQ）、运行确认（OQ）和性能确认（PQ）。（亦请参见计算机化系统指南）

4.4.   Validation and qualification should be described in protocols and recorded in reports. Reports should contain documented evidence such as screen shots, printouts or other source data of tests executed as part of validation and qualification.

验证和确认应在方案中进行说明，并记录在报告中。报告中应包括文件化证据，如截屏、打印条或其它作为验证和确认的一部分所执行检测的源数据。

4.5.   The data should provide evidence of the consistency of performance of the system, and reliable and accurate results.

数据应提供证据证明系统性能一致性，以及结果可靠准确。

4.6.   Parameters such as, but not limited to, password control, audit trail, access and privileges, should be described and verified during validation and qualification.

参数（例如但不仅限于密码控制、审计追踪、访问和权限）应在验证和确认时说明并核对。

4.7.   Chromatographic systems should be calibrated at periodic intervals in accordance with written procedures.  Records should be maintained.

色谱系统应根据书面程序定期进行校正。记录应保存。

4.8.   Root cause analysis, impact and risk assessment should be done when any calibration parameter is found out of calibration or not meeting the predefined limits. Appropriate corrective and preventive action (CAPA) should be taken.

如发现任何校正参数未校正或不符合既定限度，则应进行根本原因分析、影响性分析和风险评估。应采取适当的CAPA。

5.      ACCESS AND PRIVILEGES 访问与权限

5.1.   There should be a standard operating procedure (SOP) for the creation and deletion of user groups and users of the chromatographic system, indicating the relevant privileges allocated to each user.  Records should be maintained.

应有标准操作程序（SOP）规定色谱系统用户组和用户的创建与删除，写明配置给每个用户的相关权限。记录应保存。

5.2.   An up-to-date matrix of user groups and users should be maintained.

应维护一份用户组和用户最新清单。

5.3.   Users in each group should be appropriately qualified for the responsibility and privileges given.

每个组内的用户应有适当资质可承担指定的职责和权限。

5.4.   Manual records of user groups, users and their privileges should be concordant with electronic data.

用户组、用户及其权限的手工记录应与电子数据相一致。

5.5.   Where required, justification should be provided for privileges granted to user groups or users.

必要时，为用户组或用户授予的权限应有理由支持。

6.      AUDIT TRAIL 审计追踪

6.1.   Chromatographic systems should have (an) audit trail(s).

色谱系统应有审计追踪。

6.2.   Full audit trails should be enabled from the time of installation of software.

从软件安装开始即应全面激活审计追踪。

6.3.   Audit trails should remain enabled throughout the life cycle of a chromatographic system.

审计追踪在色谱系统的生命周期中应保持激活。

6.4.   Audit trails should be reviewed in accordance with an SOP. There should be evidence of the regular (each chromatographic analysis) and periodic review (at random checks at specified intervals) of audit trails.

审计追踪应根据SOP进行审核。应有证据证明对审计追踪进行了日常（每次色谱分析）和定期审核（按指定时间间隔随机检查）。

6.5.   Audit trails are part of metadata and should be stored as part of the data set for all chromatographic analysis.

审计追踪是元数据的一部分，应作为所有色谱分析数据系列的一部分存贮。

7.      DATE AND TIME FUNCTIONS 日期与时间功能

7.1.   Chromatographic systems should have date and time functions enabled.

色谱系统应激活日期与时间功能。

7.2.   The date and time function should be locked and access to change the date and time should be controlled.  This includes time zones.

日期和时间应锁定，修改日期和时间的权限应受控。其中包括时区。

7.3.   All actions on chromatographic systems should be date and time-tracked.

色谱系统的所有动作均应可追踪到日期和时间。

8.      ELECTRONIC SYSTEMS 电子系统

Note: This includes computerized systems

注：其中包括计算机化系统。

8.1.   Electronic systems used in chromatographic systems should be suitable for their intended use.

色谱系统所用电子系统应适合其既定用途。

8.2.   Where possible, all chromatographic systems should be linked to a network.

所有色谱系统应尽可能连接到网络。

8.3.   Stand-alone systems should be appropriately managed. Risk assessment should be done to ensure that sufficient controls are in place to eliminate the risks associated with stand- alone systems. These include, but are not limited to, access, privileges, date and time function, audit trail, back-up and data management

单机系统应进行恰当管理。应进行风险评估以确保有足够的控制用以消除单机系统带来的风险。其中包括但不仅限于访问、权限、日期和时间功能、审计追踪、备份和数据管理。

8.4.   Electronic Data Management Systems (EDMS) should be considered for the appropriate management of data, including acquisition, processing and storage of data. EDMS should be appropriate for their intended use and ensure the accuracy and reliability of data obtained and processed.

应考虑使用电子数据管理系统（EDMS）对数据进行管理，包括数据采集、处理和存贮。EDMS应适合其既定用途，确保所获取和处理的数据的准确性和可靠性。

8.5.   Appropriate procedures should be followed when a new electronic system is taken into use. Procedures should also be followed for the removal of a system from use. Records should be maintained.

在开始使用新的电子系统时应遵守适当的程序。系统退出使用时亦应遵守程序。记录应有保存。

9.      SOLVENTS, BUFFER SOLUTIONS AND MOBILE PHASES 溶剂、缓冲液和流动相

9.1.   Solvents, buffer solutions and mobile phases should be prepared, stored and used in accordance with authorized specifications, procedures and pharmacopoeia. These should be used within their validated shelf life.

溶剂、缓冲液和流动相制备、存贮和使用应根据批准的质量标准、程序和药典。应在其经过验证的货架期内使用。

9.2.   Records for their preparation should be maintained.

其配制记录应保存。

9.3.   Chemicals, reagents and other materials used should be of appropriate grade and quality.

所用化学品、试剂和其它物料应为适当级别和质量。

9.4.   Mobile phases should be filtered and degassed when required.

流动相应过滤除气（必要时）。

10.   COLUMN MANAGEMENT 色谱柱管理

10.1.  Columns used in chromatography should be appropriate for their intended use.

色谱所用柱子应适合其既定用途。

10.2. Columns should be purchased from approved suppliers.

色谱柱应从批准的供应商处采购。

10.3. Columns should be verified on receiptand checked for their suitability prior to use.

收到色谱柱时应验收，使用前应检查其是否适用性。

10.4. Columns, tubing and fittings should beappropriate to ensure that the system performs as expected.

色谱柱、管和配件应适当，以确保系统性能达到预期。

10.5. Backpressure and flow rates should be appropriate for the column to be used and specified in specifications and test procedures.

背压和流速应适合所用色谱柱，并在标准和检验方法中指定。

10.6. Column efficiency should be appropriate (number of theoretical plates) to ensure good chromatography.

柱效应适当（理论塔板数）以确保良好的色谱效果。

10.7. Risks associated with columns, such as“chiral columns”, should be controlled.

色谱柱相关风险，如“手性柱”应受控。

10.8. Flow rate, loading capacity and backpressure should be appropriate to ensure desired and constant retention time.

流速度、载量和背压应适当，以确保获得理想稳定的保留时间。

10.9. The use of columns should be recorded in a traceable manner. This includes, for example, a unique identification number, number of injections and washing.

色谱柱的使用应以可追踪的方式记录。其中包括例如唯一识别号、进针数和冲洗。

10.10. Columns should be washed (cleaned orflushed) according to defined procedures which define the steps and parameters, such as sequence and flow rate.

色谱柱应根据指定的程序清洗（清洁或冲洗），在程序中规定冲洗步骤和参数如顺序和流速。

10.11. Columns should be stored in a manner that ensures that they are not damaged.

色谱柱存贮方式应确保其不受损坏。

10.12. Equilibrating columns before, and temperature control of column and mobile phase during analysis, should be done when specified.

分析前柱平衡、分析中柱温控制和流动相如有规定应遵守。

10.13. Removal of contaminants and regeneration of columns should only be considered when the appropriate procedures for this had been developed.

只有在已制订了适当程序时，才可考虑清除色谱柱污染物和再生。

11.   SAMPLE MANAGEMENT 样品管理

11.1. Sample management (including the receiving and preparation of samples) should be considered as important aspects in good chromatography practices.

优良色谱规范中应将样品管理（包括样品接收和配制）作为重要事项考虑。

11.2. Samples for analysis, received in the laboratory, should be entered in an appropriate record which ensures the traceability of the sample details and analysis.

化验室收到分析用样品后应录入适当记录，确保样品详细信息和分析可追溯。

11.3. Samples should be stored under appropriate conditions.

样品应存贮在适当条件下。

11.4. Samples, blanks and standards should be prepared in accordance with the authorized specification or standard test procedure.  Records for the preparation should be maintained.

样品、空白和对照品应根据批准的标准或标准程序配制。配制记录应保存。

11.5. Official, secondary or working standards used should be traceable to records maintained for their purchase, preparation, storage and use.

所用官方、第二或工作对照品应可通过保存的记录追溯其采购、配制、存贮和使用情况。

11.6. Standard solutions prepared for use in chromatography should be used within their validated shelf life.

色谱所用对照溶液应在其经验证的货架期内使用。

11.7. Validated or verified (as applicable) analytical methods should be used.

应使用经过验证或确认（适用时）的分析方法。

11.8. The sample set (sample sequence) should be defined and vials with standard solution(s), sample solution and blank solution should be verified to ensure the correct sequence of injections in the chromatographic system.

应规定样品系列（样品序列），对照液、样品溶液和空白溶液进样瓶应进行核对以确保色谱系统进样序列正确。

11.9. Where carry-over or interference in analysis is relevant, suitable precautions should be taken.

如果分析可能有残留或干扰，则应采取适当的预防措施。

11.10. The use of “trial injections”, “system check injections” or other injections that are not specified as part of as ample set, is not recommended. In exceptional cases where these are employed, this should be clearly described in an authorized procedure. Only standard solutions may be used for this purpose. The electronic record of source data should be saved and stored together with the source data of the sample set for analysis.

不建议使用“试针”、“系统检查进针”或其它未规定作为样品序列一部分的进针。例外情形需要使用时，应在批准程序里清楚说明。只有对照溶液可以用于此目的。源数据的电子记录应与分析的样品序列源数据一起保存和存贮。

11.11. System suitability (SST) should be partof the sample set. The SST should be performed as described in the respective pharmacopoeia monograph or validated in-house specification and standard test procedure. SST should meet the predetermined acceptance criteria.

系统适用性（SST）应作为样品序列的一部分。应按相应药典各论或经验证的内控标准和标准检验方法执行SST。SST应符合预订的可接受标准。

11.12. Standard solution injections (bracketing standards) should be consider and included in the sample set, at defined intervals. The frequency of inclusion in a sample set should be justified.  Acceptance criteria should be set and monitored.

应考虑按指定间隔进样对照溶液（分组标准），并将其包括在样品系列中。在样品序列中进样对照溶液的频次应合理，应设置可接受标准并监测。

11.13. Acceptance criteria should be set for SST, bracketing standards, deviation from relative retention, and any other aspect that may be deemed necessary for the chromatographic analysis. This includes acceptability of peak shapes.

应设定SST、分组标准、保留时间偏差以及其它色谱分析可能必须的方面的可接受标准。其中包括峰形可接受度。

11.14. Where blank interferences are detected, these should be within limits.

如果发现有空白干扰，干扰应在限度范围内。

12.   CHROMATOGRAPHIC METHODS (ACQUISITION AND PROCESSING) 色谱方法（采集和处理）

12.1. Chromatographic methods selected should be appropriate for their intended use.

所选择的色谱方法应适合其用途。

12.2. Non-pharmacopoeia methods should be developed, validated and detailed on standard procedures.  These should be followed by qualified, experienced personnel.

非药典方法应根据标准程序开发、验证和详细说明。这些工作应由有资质有经验的人员按要求进行。

12.3. Where possible, methods should be created and saved by appointed personnel, in the chromatographic system. Methods selected for analysis should not be modified unless approved for the intended purpose by authorized personnel.

方法应尽可能由指定人员创建和保存在色谱系统中。分析所选择的方法不应进行修订，如需修订应由授权人员根据其意向目的进行批准。

12.4. Results acquired should be processed through validated methods. Where methods for acquisition and processing are different, selected methods should be traceable and reflected in the audit trail.

所采集的结果应使用经过验证的方法进行处理。如果采集方法和处理方法不同，所选方法应可追溯，并反映在审计追踪里。

12.5. Methods should be proven to remain in a validated state throughout the life cycle of the method.

应证明方法在其生命周期中始终保持经验证的状态。

13.   CHROMATOGRAPHICP EAKS 色谱峰

13.1. Chromatographic analysis should meet ALCOA+ principles.

色谱分析应符合ALCOA+原则。

13.2. Factors considered during method validation should include

方法验证中考虑的因素应包括：

•       recovery experiments;

•       回收率实验

•       slope sensitivity;

•       斜率灵敏度

•       peak width;

•       峰宽

•       bunching factor;

•       集束因子

•       area reject;

•       最小峰面积（忽略阈值）

•       noise threshold; and

•       噪声阈值

•       area threshold.

•       峰面积阈值

13.3. Peaks should be reviewed for acceptability according to policies and procedures, including recommendations and requirements from national regulatory authorities, pharmacopoeia and analytical validation.

应根据原则和程序，包括国家药监机构、药典和分析验证的建议和要求对峰的可接受度进行检查。

13.4. Where more than one column has to be used in complex analysis, the procedure and instructions should be clear in order to ensure that no errors are made during analysis.

如果在复杂分析中使用了不止一支色谱柱，程序和指令应清楚以确保在分析中不会出错。

13.5. Procedures should include the recommendations and considerations for good chromatography practices as described in this guideline, with specific reference to policies, acceptance limits (as appropriate) and ALCOA+.

程序应包括本指南中所述的优良色谱规范建议和考量，以及对原则、可接受标准（适当时）和ALCOA+的具体参考。

14.   PEAK INTEGRATION 峰积分

14.1. Peak areas  in  analytical chromatograms  should  be accurately  and  consistently integrated in a scientifically sound manner.

分析色谱中的峰面积积分应准确一致、科学合理。

14.2. Where possible, HPLC and GC instruments should be interfaced with computerised chromatographic data capturing and processing systems which are capable of performing the integration process automatically.

如果可能，HPLC和GC仪器应与能自动进行积分处理的计算机化色谱数据采集和处理系统设置接口。

14.3. The same integration parameters shouldbe applied to all peaks in a sample set or sample sequence unless otherwise scientifically justifiable.

除另有科学论证外，同一样品序列或样品序列中的所有峰均应使用相同的积分参数。

14.4. Personnel should select appropriate values for the parameters (such as, slope sensitivity, noise threshold, peak width, area threshold and bunching factor and skim ratio) which are used by the processing software to define the respective chromatographic peaks.

应选择适当的参数值（如斜率灵敏度、噪声阈值、峰宽、峰面积阈值和集束因子及撇去比率）在处理软件中定义相应的色谱峰。

14.5. To facilitate the accurate integration of chromatographic peaks, it is necessary that all of the peaks are fully separated. If quantitative data must be obtained from unseparated peaks, the laboratory should have clear policies as to how such peaks should be integrated. This should include a description as to when it is acceptable to use different functions for integrating unresolved peaks, such as:

为便于对色谱峰进行准确积分，有必要将所有峰完全分离。如果必须从未分开的峰中获得定量数据，则实验室应制订明确的方针说明如何对这些峰进行积分。其中应包括阐明何时可使用不同函数对未分离的峰进行积分，如：

•       tangential skim;

•       切线撇去

•       exponential skim;

•       指数撇去

•       exponential curve fitting;

•       指数曲线设置

•       straight line skim;

•       直线撇去

•       front peak skim;

•       前伸峰撇去

•       rear peak skim;

•       拖尾峰撇去

•       peak valley ratio; and

•       峰谷比

•       valley height ratio.

•       峰高比

14.6. Validated methods, specified chromatographic conditions and good chromatography practices should facilitate obtaining symmetrical peaks. Where fronting, tailing, split peaks or other types of peaks are observed, these should be investigated, the root cause identified and appropriate CAPA taken.

经过验证的方法、具体的色谱条件和优良色谱规范有助于获得对称峰。如果发现有前伸峰、拖尾峰、分裂峰或其它类型的峰，应进行调查，找出根本原因并采取适当的CAPA。

14.7. Where manual integration has to be done, authorized procedures should be followed. Records should be maintained which include the authorization and justification for manual integration.

如果必须进行手动积分，则应遵守经过批准的程序。应保存记录，其中包括手动积分的批准和理由。

14.8. Using a procedure to integrate peak height or area by manually setting the baseline using chromatographic software should only be allowed in exceptional cases. Only a selected number of users should be granted privileges to do so. Records and justification should be given when this procedure is followed.

只有例外情形下，才可使用程序在利用色谱软件进行手动基线设置后对峰高或峰面积积分。

14.9. Where smoothing is applied, the typeof “filter” used and extent of smoothing should be justified.

如果做了平滑处理，所用“筛选”类型和平滑处理的程度应进行论证。

15.   CLEANING VALIDATION 清洁验证

Note. For recommendations relating to cleaning validation, see Annex 4, Supplementary Guidelines on Good Manufacturing Practices: Validation (WHO Technical Report Series, No. 937, 2006, Appendix 3).

注：关于清洁验证的建议参见附录4“GMP补充指南：验证”（WHO第937号技术报告，2006，附录3）。

15.1. Where possible, specific methods should be developed, validated and then used in cleaning validation and cleaning verification.

应尽可能开发、验证具有专属性的方法，然后用于清洁验证和清洁确认中。

15.2. Chromatographic methods selected should be specific and appropriate to detect the presence of the substance to be analysed.

所选色谱方法应具有专属性，适合于检出分析对象。

15.3. Data and results should be managed in accordance with these guidelines and other relevant guidelines relating to cleaning validation, chromatography and applicable chapters in pharmacopoeia.

数据和结果应根据本指南和其它与清洁验证、色谱和药典适用章节中相关指南进行管理。

15.4. Data and results should be retained for appropriate times to enable inspection thereof.

数据和结果应保存适当时长以备相应检查。

16.   DATA MANAGEMENT 数据管理

16.1. Chromatographic data acquired should be attributable, legible, original and accurate.

所获取的色谱数据应可追溯、清晰、原始和准确。

16.2. Procedures should be followed for the processing of data and reporting of results.

数据处理和结果报告应按程序执行。

16.3. Data should be backed up according to procedures and records maintained as proof thereof. Special care should betaken to ensure frequent back up of data from stand-alone systems to prevent loss of data.

数据应根据程序备份，记录应保存作为证据。应特别注意确保单机系统数据备份要频繁，以防止数据遗失。

16.4. Data should be safely stored, including control over access to data. Backed-up data should be randomly selected for restoration and verification, at defined intervals.

数据应安全存贮，包括对数据访问进行控制。备份数据应按指定时间间隔随机抽取进行恢复和验证。

16.5. Where appropriate, hard copies of data (including metadata) and results should be retained as part of the analytical report reflecting analysis performed.

适当时，数据（包括元数据）和结果纸质副本应保存作为反映已执行分析的分析报告的一部分。

Note:  See other guidelines addressing  computerized systems,  data  integrity and  good documentation practices.

注：参见其它计算机化系统、数据完整性和优良文件规范的指南。

16.6. Procedures should be in place to allow for recovery of chromatographic data in case of disasters such as instrument failure, viruses, hardware or software failure and power failure.

应有程序规定在灾难（如仪器故障、病毒、硬件或软件故障和断电）发生时可恢复色谱数据。

16.7. Complete data should be retained for appropriate periods of time to allow for data verification, registration or other reasons.

完整数据应保存适当时长，期间可进行数据核查、注册或其它理由。

Acronyms 术语

ALCOA	attributable, legible,  contemporaneous, originalandaccurate	可追溯性、清晰、同步、原始和准确
CAPA	corrective and preventiveaction	纠正与预防措施
DQ	design qualification	设计确认
EDMS	Electronic Data Management Systems	电子数据管理系统
FAT	factoryacceptance test	工厂接收测试
GC	gaschromatography	气相色谱
HPLC	High PressureLiquid Chromatography	高压液相色谱
IQ	installation qualification	安装确认
OQ	operational qualification	运行确认
PQ	performance qualification	性能确认
SAT	site acceptance test	用户接收测试
SOP	standard operatingprocedure	标准操作规程
SST	system suitability	系统适用性
URS	user requirement  specifications	用户需求手册

Further reading 延伸阅读

•  The International Pharmacopoeia,http://apps.who.int/phint/2018/index.html

• 国际药典

• European Pharmacopoeia,https://www.edqm.eu/en/european-pharmacopoeia-ph-eur-9th-  edition

• 欧洲药典

• United States Pharmacopoeia,http://www.usp.org/

• 美国药典USP

• Appendix 5: Validation of ComputerizedSystems Annex 3 (Technical Report Series No. XX, Annex 3, 2019)

• 附录5：计算机化系统验证附录3（第XX号技术报告，附录3，2019）

• Guidance on Good Data and Record ManagementPractices (WHO Technical Report Series No. 996, 2016, Annex 5)

• 优良数据和记录管理规范指南（WHO第996号技术报告，2016，附录5）

***