近日，WHO發(fā)布了《 GOOD CHROMOTOGRAPHY PRACTICES優(yōu)良色譜規(guī)范》，該文件對(duì)色譜系統(tǒng)、驗(yàn)證確認(rèn)、訪問與權(quán)限、審計(jì)追蹤、時(shí)間日期功能、電子系統(tǒng)、溶劑、緩沖液、流動(dòng)相、色譜柱、樣品的管理、色譜方法、色譜峰和峰積分、數(shù)據(jù)管理等作了較為系統(tǒng)的要求，此外，還專門清潔驗(yàn)證的分析方法、數(shù)據(jù)管理作出規(guī)定。

該文件全文翻譯如下：

1.      INTRODUCTION AND SCOPE

介紹與范圍

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.

近年來色譜方法（如高壓液相色譜（HPLC）和氣相色譜（GC））的使用在QC實(shí)驗(yàn)室分析中已有顯著增加。

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，物料和產(chǎn)品鑒別、物料和產(chǎn)品中含量和有關(guān)物質(zhì)檢測(cè)，以及驗(yàn)證如工藝驗(yàn)證和清潔驗(yàn)證。

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).

由于通過色譜獲得的結(jié)果非常關(guān)鍵，生產(chǎn)商應(yīng)確保所獲取的數(shù)據(jù)的準(zhǔn)確性和可靠性。結(jié)果應(yīng)符合ALCOA+原則（即可追溯、清晰、同步、原始和準(zhǔn)確）。

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譜系統(tǒng)進(jìn)行樣品分析時(shí)需要考慮的優(yōu)良規(guī)范。在分析如原料、起始物料、中間體、中控物料和成品中應(yīng)使用這些原則。

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.

本指南中人原則適用于如含量檢測(cè)、有關(guān)物質(zhì)和雜質(zhì)檢測(cè)、工藝驗(yàn)證、清潔驗(yàn)證、清潔確認(rèn)和穩(wěn)定性測(cè)試中所用的所有類型色譜分析。

2.      GLOSSARY

術(shù)語解釋

3.      CHROMATOGRAPHIC SYSTEMS

色譜系統(tǒng)

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

生產(chǎn)商應(yīng)選擇、安裝和使用適合其既定用途的色譜系統(tǒng)。

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

供應(yīng)商確認(rèn)應(yīng)確保硬件和軟件適合其既定應(yīng)用程序，能提供售后服務(wù)。

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

購買方和供應(yīng)商之前應(yīng)有有效協(xié)議說明雙方職責(zé)。

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.

系統(tǒng)應(yīng)符合法規(guī)要求和GMP要求，包括但不僅限于，確保數(shù)據(jù)采集、處理和存貯符合國(guó)家法律和ALCOA+原則。

4.      QUALIFICATION AND VALIDATION

確認(rèn)與驗(yàn)證

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

色譜系統(tǒng)驗(yàn)證和確認(rèn)的范圍和程度應(yīng)根據(jù)風(fēng)險(xiǎn)管理原則確定。

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

驗(yàn)證和確認(rèn)方法及其執(zhí)行應(yīng)在批準(zhǔn)的文件如驗(yàn)證主計(jì)劃中闡明。

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).

確認(rèn)的所有階段均應(yīng)考慮包括如用戶需求手冊(cè)（URS）、設(shè)計(jì)確認(rèn)（DQ）、工廠接收測(cè)試（FAT）、用戶接收測(cè)試（SAT）、安裝確認(rèn)（IQ）、運(yùn)行確認(rèn)（OQ）和性能確認(rèn)（PQ）。（亦請(qǐng)參見計(jì)算機(jī)化系統(tǒng)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.

驗(yàn)證和確認(rèn)應(yīng)在方案中進(jìn)行說明，并記錄在報(bào)告中。報(bào)告中應(yīng)包括文件化證據(jù)，如截屏、打印輸出或其它作為驗(yàn)證和確認(rèn)的一部分所執(zhí)行檢測(cè)的源數(shù)據(jù)。

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

數(shù)據(jù)應(yīng)提供證據(jù)證明系統(tǒng)性能一致性，以及結(jié)果可靠準(zhǔn)確。

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.

參數(shù)（例如但不僅限于密碼控制、審計(jì)追蹤、訪問和權(quán)限）應(yīng)在驗(yàn)證和確認(rèn)時(shí)說明并核對(duì)。

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

色譜系統(tǒng)應(yīng)根據(jù)書面程序定期進(jìn)行校正。記錄應(yīng)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.

如發(fā)現(xiàn)任何校正參數(shù)超出校準(zhǔn)范圍或不符合既定限度，則應(yīng)進(jìn)行根本原因分析、影響性分析和風(fēng)險(xiǎn)評(píng)估。應(yīng)采取適當(dāng)?shù)腃APA。

5.      ACCESS AND PRIVILEGES 

訪問與權(quán)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.

應(yīng)有標(biāo)準(zhǔn)操作程序（SOP）規(guī)定色譜系統(tǒng)用戶組和用戶的創(chuàng)建與刪除，寫明為每個(gè)用戶所分配的權(quán)限。記錄應(yīng)保存。

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

應(yīng)維護(hù)一份用戶組和用戶最新清單。

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

每個(gè)組內(nèi)的用戶應(yīng)有適當(dāng)資質(zhì)可承擔(dān)指定的職責(zé)和權(quán)限。

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

用戶組、用戶及其權(quán)限的手工記錄應(yīng)與電子數(shù)據(jù)相一致。

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

用戶組或用戶所分配的權(quán)限應(yīng)提供依據(jù)，如需要。

6.      AUDIT TRAIL

審計(jì)追蹤

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

色譜系統(tǒng)應(yīng)有審計(jì)追蹤。

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

從軟件安裝開始即應(yīng)全面激活審計(jì)追蹤。

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

審計(jì)追蹤在色譜系統(tǒng)的生命周期中應(yīng)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.

審計(jì)追蹤應(yīng)根據(jù)SOP進(jìn)行審核。應(yīng)有證據(jù)證明對(duì)審計(jì)追蹤進(jìn)行了日常（每次色譜分析）和定期審核（按指定時(shí)間間隔隨機(jī)檢查）。

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

審計(jì)追蹤是元數(shù)據(jù)的一部分，應(yīng)作為所有色譜分析數(shù)據(jù)系列的一部分存貯。

7.      DATE AND TIME FUNCTIONS

日期與時(shí)間功能

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

色譜系統(tǒng)應(yīng)激活日期與時(shí)間功能。

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.

日期和時(shí)間應(yīng)鎖定，修改日期和時(shí)間的權(quán)限應(yīng)受控，包括時(shí)區(qū)。

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

色譜系統(tǒng)的所有動(dòng)作均應(yīng)可追蹤到日期和時(shí)間。

8.      ELECTRONIC SYSTEMS

電子系統(tǒng)

Note: This includes computerized systems

注：這也包括計(jì)算機(jī)化系統(tǒng)。

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

色譜系統(tǒng)所用電子系統(tǒng)應(yīng)適合其既定用途。

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

所有色譜系統(tǒng)應(yīng)盡可能連接到網(wǎng)絡(luò)。

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

單機(jī)系統(tǒng)應(yīng)進(jìn)行恰當(dāng)管理。應(yīng)進(jìn)行風(fēng)險(xiǎn)評(píng)估以確保有足夠的控制用以消除單機(jī)系統(tǒng)帶來的風(fēng)險(xiǎn)。其中包括但不僅限于訪問、權(quán)限、日期和時(shí)間功能、審計(jì)追蹤、備份和數(shù)據(jù)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.

應(yīng)考慮使用電子數(shù)據(jù)管理系統(tǒng)（EDMS）對(duì)數(shù)據(jù)進(jìn)行管理，包括數(shù)據(jù)采集、處理和存貯。EDMS應(yīng)適合其既定用途，確保所獲取和處理的數(shù)據(jù)的準(zhǔn)確性和可靠性。

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.

新的電子系統(tǒng)在投入使用應(yīng)遵守適當(dāng)?shù)某绦?。系統(tǒng)退役也應(yīng)遵守程序。記錄應(yīng)有保存。

9.      SOLVENTS, BUFFER SOLUTIONS AND MOBILE PHASES

溶劑、緩沖液和流動(dòng)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.

溶劑、緩沖液和流動(dòng)相制備、存貯和使用應(yīng)根據(jù)批準(zhǔn)的質(zhì)量標(biāo)準(zhǔn)、程序和藥典。應(yīng)在其經(jīng)過驗(yàn)證的有效期內(nèi)使用。

9.2.   Records for their preparation should be maintained.

配制記錄應(yīng)保存。

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

所用化學(xué)品、試劑和其它物料應(yīng)為適當(dāng)級(jí)別和質(zhì)量。

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

流動(dòng)相應(yīng)過濾除氣（必要時(shí)）。

10.   COLUMN MANAGEMENT

色譜柱管理

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

色譜所用柱子應(yīng)適合其既定用途。

10.2. Columns should be purchased from approved suppliers.

色譜柱應(yīng)從批準(zhǔn)的供應(yīng)商處采購。

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

收到色譜柱時(shí)應(yīng)驗(yàn)收，使用前應(yīng)檢查其是否適用性。

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

色譜柱、管和配件應(yīng)適當(dāng)，以確保系統(tǒng)性能達(dá)到預(yù)期。

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

背壓和流速應(yīng)適合所用色譜柱，并在標(biāo)準(zhǔn)和檢驗(yàn)方法中指定。

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

柱效應(yīng)適當(dāng)（理論塔板數(shù)）以確保良好的色譜效果。

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

色譜柱相關(guān)風(fēng)險(xiǎn)，如“手性柱”應(yīng)受控。

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

流速度、載量和背壓應(yīng)適當(dāng)，以確保獲得理想穩(wěn)定的保留時(shí)間。

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.

色譜柱的使用應(yīng)以可追蹤的方式記錄。其中包括例如唯一識(shí)別號(hào)、進(jìn)針數(shù)和沖洗。

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

色譜柱應(yīng)根據(jù)指定的程序清洗（清潔或沖洗），在程序中規(guī)定沖洗步驟和參數(shù)如順序和流速。

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

色譜柱存貯方式應(yīng)確保其不受損壞。

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、分析中柱溫控制和流動(dòng)相如有規(guī)定應(yīng)遵守。

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

只有在已制訂了適當(dāng)程序時(shí)，才可考慮清除色譜柱污染物和再生。

11.   SAMPLE MANAGEMENT

樣品管理

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

優(yōu)良色譜規(guī)范中應(yīng)將樣品管理（包括樣品接收和配制）作為重要事項(xiàng)考慮。

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.

化驗(yàn)室收到分析用樣品后應(yīng)錄入適當(dāng)記錄，確保樣品詳細(xì)信息和分析可追溯。

11.3. Samples should be stored under appropriate conditions.

樣品應(yīng)存貯在適當(dāng)條件下。

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.

樣品、空白和對(duì)照品應(yīng)根據(jù)批準(zhǔn)的標(biāo)準(zhǔn)或標(biāo)準(zhǔn)程序配制。配制記錄應(yīng)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、第二或工作對(duì)照品應(yīng)可通過保存的記錄追溯其采購、配制、存貯和使用情況。

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

色譜所用對(duì)照溶液應(yīng)在其經(jīng)驗(yàn)證的貨架期內(nèi)使用。

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

應(yīng)使用經(jīng)過驗(yàn)證或確認(rèn)（適用時(shí)）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.

應(yīng)規(guī)定樣品系列（樣品序列），對(duì)照液、樣品溶液和空白溶液進(jìn)樣瓶應(yīng)進(jìn)行核對(duì)以確保色譜系統(tǒng)進(jìn)樣序列正確。

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

如果分析可能有殘留或干擾，則應(yīng)采取適當(dāng)?shù)念A(yù)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.

不建議使用“試針”、“系統(tǒng)檢查進(jìn)針”或其它未規(guī)定作為樣品序列一部分的進(jìn)針。例外情形需要使用時(shí)，應(yīng)在批準(zhǔn)程序里清楚說明。只有對(duì)照溶液可以用于此目的。源數(shù)據(jù)的電子記錄應(yīng)與分析的樣品序列源數(shù)據(jù)一起保存和存貯。

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.

系統(tǒng)適用性（SST）應(yīng)作為樣品序列的一部分。應(yīng)按相應(yīng)藥典各論或經(jīng)驗(yàn)證的內(nèi)控標(biāo)準(zhǔn)和標(biāo)準(zhǔn)檢驗(yàn)方法執(zhí)行SST。SST應(yīng)符合預(yù)訂的可接受標(biāo)準(zhǔn)。

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.

應(yīng)考慮按指定間隔進(jìn)樣對(duì)照溶液（分組標(biāo)準(zhǔn)），并將其包括在樣品系列中。在樣品序列中進(jìn)樣對(duì)照溶液的頻次應(yīng)合理，應(yīng)設(shè)置可接受標(biāo)準(zhǔn)并監(jiān)測(cè)。

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.

應(yīng)設(shè)定SST、分組標(biāo)準(zhǔn)、保留時(shí)間偏差以及其它色譜分析可能必須的方面的可接受標(biāo)準(zhǔn)。其中包括峰形可接受度。

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

如果發(fā)現(xiàn)有空白干擾，干擾應(yīng)在限度范圍內(nèi)。

12.   CHROMATOGRAPHIC METHODS (ACQUISITION AND PROCESSING) 

色譜方法（采集和處理）

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

所選擇的色譜方法應(yīng)適合其用途。

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

非藥典方法應(yīng)根據(jù)標(biāo)準(zhǔn)程序開發(fā)、驗(yàn)證和詳細(xì)說明。這些工作應(yīng)由有資質(zhì)有經(jīng)驗(yàn)的人員按要求進(jìn)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.

方法應(yīng)盡可能由指定人員創(chuàng)建和保存在色譜系統(tǒng)中。分析所選擇的方法不應(yīng)進(jìn)行修訂，如需修訂應(yīng)由授權(quán)人員根據(jù)其意向目的進(jìn)行批準(zhǔn)。

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.

所采集的結(jié)果應(yīng)使用經(jīng)過驗(yàn)證的方法進(jìn)行處理。如果采集方法和處理方法不同，所選方法應(yīng)可追溯，并反映在審計(jì)追蹤里。

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

應(yīng)證明方法在其生命周期中始終保持已驗(yàn)證狀態(tài)。

13.   CHROMATOGRAPHICP EAKS 

色譜峰

13.1. Chromatographic analysis should meet ALCOA+ principles.

色譜分析應(yīng)符合ALCOA+原則。

13.2. Factors considered during method validation should include

方法驗(yàn)證中考慮的因素應(yīng)包括：

·       recovery experiments;

·       回收率實(shí)驗(yàn)

·       slope sensitivity;

·       斜率靈敏度

·       peak width;

·       峰寬

·       bunching factor;

·       集束因子

·       area reject;

·       最小峰面積（忽略閾值）

·       noise threshold; and

·       噪聲閾值

·       area threshold.

·       峰面積閾值

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.

應(yīng)根據(jù)原則和程序，包括國(guó)家藥監(jiān)機(jī)構(gòu)、藥典和分析驗(yàn)證的建議和要求對(duì)峰的可接受度進(jìn)行檢查。

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.

如果在復(fù)雜的色譜分析中使用了不止一支色譜柱，其程序和指令應(yīng)清楚以確保在分析中不會(huì)出錯(cuò)。

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+.

程序應(yīng)包括本指南中所述的優(yōu)良色譜規(guī)范建議和考量，以及對(duì)原則、可接受標(biāo)準(zhǔn)（適當(dāng)時(shí)）和ALCOA+的具體參考。

14.   PEAK INTEGRATION

峰積分

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

分析色譜中的峰面積積分應(yīng)準(zhǔn)確一致、科學(xué)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儀器應(yīng)與能自動(dòng)進(jìn)行積分處理的計(jì)算機(jī)化色譜數(shù)據(jù)采集和處理系統(tǒng)設(shè)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.

除另有科學(xué)論證外，同一樣品序列或樣品序列中的所有峰均應(yīng)使用相同的積分參數(shù)。

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.

應(yīng)選擇適當(dāng)?shù)膮?shù)值（如斜率靈敏度、噪聲閾值、峰寬、峰面積閾值和集束因子及撇去比率）在處理軟件中定義相應(yīng)的色譜峰。

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:

為便于對(duì)色譜峰進(jìn)行準(zhǔn)確積分，有必要將所有峰完全分離。如果必須從未分開的峰中獲得定量數(shù)據(jù)，則實(shí)驗(yàn)室應(yīng)制訂明確的方針說明如何對(duì)這些峰進(jìn)行積分。其中應(yīng)包括闡明何時(shí)可使用不同函數(shù)對(duì)未分離的峰進(jìn)行積分，如：

·       tangential skim;

·       切線撇去

·       exponential skim;

·       指數(shù)撇去

·       exponential curve fitting;

·       指數(shù)曲線設(shè)置

·       straight line skim;

·       直線撇去

·       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.

經(jīng)過驗(yàn)證的方法、具體的色譜條件和優(yōu)良色譜規(guī)范有助于獲得對(duì)稱峰。如果發(fā)現(xiàn)有前伸峰、拖尾峰、分裂峰或其它類型的峰，應(yīng)進(jìn)行調(diào)查，找出根本原因并采取適當(dāng)?shù)腃APA。

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.

如果必須進(jìn)行手動(dòng)積分，則應(yīng)遵守經(jīng)過批準(zhǔn)的程序。應(yīng)保存記錄，其中包括手動(dòng)積分的批準(zhǔn)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譜軟件進(jìn)行手動(dòng)基線設(shè)置后對(duì)峰高或峰面積積分。

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

如果做了平滑處理，所用“篩選”類型和平滑處理的程度應(yīng)進(jìn)行論證。

15.   CLEANING VALIDATION 

清潔驗(yàn)證

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：關(guān)于清潔驗(yàn)證的建議參見附錄4“GMP補(bǔ)充指南：驗(yàn)證”（WHO第937號(hào)技術(shù)報(bào)告，2006，附錄3）。

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

應(yīng)盡可能開發(fā)、驗(yàn)證具有專屬性的方法，然后用于清潔驗(yàn)證和清潔確認(rèn)中。

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

所選色譜方法應(yīng)具有專屬性，適合于檢出分析對(duì)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.

數(shù)據(jù)和結(jié)果應(yīng)根據(jù)本指南和其它與清潔驗(yàn)證、色譜和藥典適用章節(jié)中相關(guān)指南進(jìn)行管理。

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

數(shù)據(jù)和結(jié)果應(yīng)保存適當(dāng)時(shí)長(zhǎng)以備相應(yīng)檢查。

16.   DATA MANAGEMENT

數(shù)據(jù)管理

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

所獲取的色譜數(shù)據(jù)應(yīng)可追溯、清晰、原始和準(zhǔn)確。

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

數(shù)據(jù)處理和結(jié)果報(bào)告應(yīng)按程序執(zhí)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.

數(shù)據(jù)應(yīng)根據(jù)程序備份，記錄應(yīng)保存作為證據(jù)。應(yīng)特別注意確保單機(jī)系統(tǒng)數(shù)據(jù)備份要頻繁，以防止數(shù)據(jù)遺失。

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.

數(shù)據(jù)應(yīng)安全存貯，包括對(duì)數(shù)據(jù)訪問進(jìn)行控制。備份數(shù)據(jù)應(yīng)按指定時(shí)間間隔隨機(jī)抽取進(jìn)行恢復(fù)和驗(yàn)證。

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

適當(dāng)時(shí)，數(shù)據(jù)（包括元數(shù)據(jù)）和結(jié)果紙質(zhì)副本應(yīng)保存作為反映已執(zhí)行分析的分析報(bào)告的一部分。

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

注：參見其它計(jì)算機(jī)化系統(tǒng)、數(shù)據(jù)完整性和優(yōu)良文件規(guī)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.

應(yīng)有程序規(guī)定在災(zāi)難（如儀器故障、病毒、硬件或軟件故障和斷電）發(fā)生時(shí)可恢復(fù)色譜數(shù)據(jù)。

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

完整數(shù)據(jù)應(yīng)保存適當(dāng)時(shí)長(zhǎng)，期間可進(jìn)行數(shù)據(jù)核查、注冊(cè)或其它理由。