近日，EDQM-OMCL發(fā)布《紫外 - 可見分光光度計確認指南》，包含Level III定期及有動機的儀器檢查、紫外 - 可見分光光度計的建議及相關典型接受限、Level IV在用儀器檢查、一般注意事項、光譜狹縫寬度（如適用）、波長精度、基線噪聲、光度漂移等內(nèi)容。文件將于9月1日生效。

 

 

 

ANNEX 3 OF THE OMCL NETWORK GUIDELINE “QUALIFICATION OF EQUIPMENT”

OMCL設備確認指南附錄3

QUALIFICATION OF UV - VISIBLE SPECTROPHOTOMETERS
紫外-可見分光光度計的確認

 

Note: Mandatory requirements in this annex are defined using the terms “shall” or “must”. The use of “should” indicates a recommendation. For these parts of the text other appropriately justified approaches are acceptable. The term “can” indicates a possibility or an example with non - binding character.
注：本附件中的強制性要求使用 “應” 或 “必須” 等詞來定義。“宜” 的使用表示一種建議。對于文本的這些部分，其他有適當理由的方法是可接受的。“可” 一詞表示一種可能性或一個不具約束力的示例。

 

Table of Contents
目錄

Introduction
簡介

Level III. Periodic and motivated instrument checks
三級：定期及有動機的儀器檢查

Recommendations for UV - visible spectrophotometers and related typical acceptance limits
紫外 - 可見分光光度計的建議及相關典型接受限

Level IV. In - use instrument checks
四級：使用中儀器檢查

Recommendations for UV - visible spectrophotometers and related typical acceptance limits
紫外 - 可見分光光度計的建議及相關典型接受限

Level III. Periodic and motivated instrument checks
三級：定期及有動機的儀器檢查

General Considerations

一般注意事項

Spectral Slit Width (if applicable)

光譜狹縫寬度（如適用）

Wavelength Precision (for mechanically set wavelengths)

波長精度（對于機械設定波長）

Baseline Noise

基線噪聲

Photometric Drift

光度漂移

Level IV. In - use instrument checks
四級：使用中儀器檢查

 

Introduction

簡介

 

The present document is the 3rd Annex of the core document “Qualification of Equipment”, and it shall be used in combination with it when planning, performing and documenting the UV - Visible spectrophotometer qualification process.
本文件是核心文件 “設備確認” 的第 3 個附件，在規(guī)劃、執(zhí)行和記錄紫外 - 可見分光光度計確認過程時，應與該核心文件結(jié)合使用。

 

The core document contains the Introduction and general forms for Level I (Selection of instruments and suppliers) and II (Installation and release for use) of qualification, which are common to all types of instruments.
核心文件包含一級（儀器和供應商的選擇）和二級（安裝和投入使用）確認的簡介和通用表格，這些適用于所有類型的儀器。

 

The present Annex 3 contains the Introduction and requirements for UV - Visible spectrophotometers. Level III (Periodic and motivated instrument calibration/checks) and IV (In - use instrument checks) qualifications must be carried out being ISO/IEC 17025 requirement.
本附件 3 包含紫外 - 可見分光光度計的簡介和要求。三級（定期及有動機的儀器校準 / 檢查）和四級（使用中儀器檢查）確認必須按照 ISO/IEC 17025 要求進行。

 

Requirements (if applicable) corresponding typical acceptance limits given in bold should be applied; however other appropriately justified approaches are acceptable.
應采用（如適用）以粗體給出的相應典型接受限；然而，其他有適當理由的方法也是可接受的。

 

Exemplary procedures provided in this document have non - binding character. They can be helpful to carry out the required qualification. Nevertheless, it is left to the professional judgement and background experience of each OMCL to decide on the most relevant procedures to be undertaken in order to give evidence that their UV-Visible spectrophotometers are working properly and aresuitable for their intended use.

本文件中提供的示例程序不具約束力。它們可能有助于進行所需的確認。然而，由每個 OMCL 根據(jù)專業(yè)判斷和背景經(jīng)驗來決定采用最相關的程序，以證明其紫外 - 可見分光光度計工作正常且適合其預期用途。

 

If the qualification of equipment is done by the manufacturer or an external service - provider, it is the responsibility of the OMC L to make sure that this is in line with the requirements set out in this guideline.
如果設備的確認是由制造商或外部服務提供商完成的，那么 OMCL 有責任確保其符合本指南中規(guī)定的要求。

 

Level III. Periodic and motivated instrument checks
三級 定期及有動機的儀器檢查

 

recommendations for UV - visible spectrometers and related typical acceptance limits
對紫外 - 可見分光光度計的建議及相關典型接受限度

EDQM發(fā)布《紫外-可見分光光度計確認指南》

following the instructions given in Ph. Eur. Chapter 2.2.25. "Control of equipment performance"
遵循《歐洲藥典》第 2.2.25 章 “設備性能控制” 中給出的說明

 

Level IV. In - use instrument checks
四級 使用中儀器的檢查

 

Recommendations for UV - visible spectrophotometers and related typical acceptance limits
紫外 - 可見分光光度計的建議以及相關典型的可接受限度

EDQM發(fā)布《紫外-可見分光光度計確認指南》

 

following the instructions given in Ph. Eur. Chapter 2.2.25. "Control of cuvettes"
按照歐洲藥典第 2.2.25 章 “比色皿的控制” 中給出的說明操作

 

Level III. Periodic and motivated instrument checks
第三級：定期及有動機的儀器檢查

 

This section contains practical examples of tests and their associated acceptance limits for several parameters related to the performance of a UV - visible spectrophotometer. These examples can be considered as the OPCs as possible approaches to perform the Level III of the equipment qualification process: "Periodic and motivated instrument checks".
本節(jié)包含了與紫外 - 可見分光光度計性能相關的幾個參數(shù)的測試實例及其相關的合格限。這些實例可被視為執(zhí)行設備確認過程第三級 “定期及有動機的儀器檢查” 的可能方法（即操作規(guī)范條件）。

 

1.General Considerations

一般注意事項

 

Measurements made by comparing samples against external standards should be made under conditions during which temperature is held constant. This is particularly relevant where the carrier solvent is organic and measurements may be distorted by expansion or evaporation of the solvent.
通過將樣品與外部標準進行比較而進行的測量應在溫度保持恒定的條件下進行。這在載液為有機溶劑且測量可能因溶劑的膨脹或蒸發(fā)而失真的情況下尤為重要。

It is recommended to perform the qualification within the spectral range corresponding to the region of analytical interest.

建議在與分析感興趣區(qū)域相對應的光譜范圍內(nèi)進行確認。

Ensure that the spectrophotometer has stabilised, according to the manufacturer's recommendations, before starting the qualification tests.

根據(jù)制造商的建議，在開始確認測試之前，確保分光光度計已穩(wěn)定。

When references are made to the European Pharmacopoeia, e.g. reagents R, then reagent quality shall comply with the Ph. Eur. specifications.

當引用《歐洲藥典》時，例如試劑 R，那么試劑質(zhì)量應符合《歐洲藥典》的規(guī)范。

When using commercial filters as alternative to the proposed tests, a set of filters covering the entire range of interest should be used. They should be calibrated with traceability to national/international standards, preferably through a national metrology laboratory or NIST.

當使用商業(yè)濾光片替代建議的測試時，應使用一組覆蓋整個感興趣范圍的濾光片。它們應可溯源至國家 / 國際標準進行校準，最好通過國家計量實驗室或美國國家標準與技術(shù)研究院（NIST）進行。

 

2.Spectral Slit Width (if applicable)

光譜狹縫寬度（如適用）

 

When using an instrument on which the slit - width is variable at the selected wavelength, the slit width must be small compared with the half - width of the absorption band but it must be as large as possible to obtain a high value of Ia. Therefore, a slit - width is chosen such that further reduction does not result in a change in absorbance reading.
當使用在選定波長下狹縫寬度可變的儀器時，狹縫寬度必須與吸收帶的半寬度相比很小，但又必須盡可能大以獲得高的 Ia 值。因此，選擇的狹縫寬度應使得進一步減小不會導致吸光度讀數(shù)的變化。

 

Method and Limits
方法和限度

 

1.Switch the system on and start the Scan module.

開啟系統(tǒng)并啟動掃描模塊。

2.Select SETUP and set the following parameters:

選擇 “設置” 并設置以下參數(shù)：

 

X Mode = Nanometers

X 模式 = 納米

Start wavelength = 650.0 nm

起始波長 = 650.0 納米

Stop wavelength = 660.0 nm

終止波長 = 660.0 納米

Scan mode = Single

掃描模式 = 單次

Scan rate = 100 nm/min

掃描速率 = 100 納米 / 分鐘

Gain = (100) see 4 below

增益 = （100）見下面第 4 點

 

3.Select Options tab and set the following parameters:

選擇 “選項” 選項卡并設置以下參數(shù)：

 

SWB = 4 nm

狹縫寬度帶寬 = 4 納米

Scan mode = Single front

掃描模式 = 單次前向

Lamps on = Deuterium

燈開啟 = 氘燈

Source change = 700.0 nm

光源切換 = 700.0 納米

 

4.Start a scan and examine the trace for a spectral peak around 656.1 nm. If no peak is seen or it is less than 50 % T, increase the gain.

開始掃描并檢查在 656.1 納米附近的光譜峰的軌跡。如果看不到峰或其小于 50% 透光度（T），則增加增益。

 

5.Measure the width of the peak (in nanometres) at half the height of the peak.
測量峰高一半處的峰寬（單位：納米）。

 

This represents the spectral bandwidth and should be within ± 10% of that selected via the computer.
這代表光譜帶寬，其值應在通過計算機選擇的值的 ±10% 范圍內(nèi)。

 

6.Check the calibration at a slit width of 0.2 nm.
在狹縫寬度為 0.2 納米時檢查校準情況。

 

If the measured slits are too small then, for a selected width, the instrument will have more photometric noise than normal.
如果測量的狹縫過小，那么對于選定的寬度，儀器將產(chǎn)生比正常情況更多的光度噪聲。

 

If the slit width is unacceptable, then reset the slit calibration.
如果狹縫寬度不可接受，則重置狹縫校準。

EDQM發(fā)布《紫外-可見分光光度計確認指南》

Effect of spectral slit width on absorbance fluctuation (performed with pure solvents).
光譜狹縫寬度對吸光度波動的影響（使用純?nèi)軇┻M行）。

EDQM發(fā)布《紫外-可見分光光度計確認指南》

 

3.Wavelength Precision (for mechanically set wavelengths)

3. 波長精度（針對機械設定波長）

 

Materials:
材料：

 

For this test, the same materials of the previous test can be used: Holmium perchlorate solution R prepared, for example, with a 40 g/L solution of holmium oxide R in a solution of perchloric acid R containing 141 g/L of HClO4 (Ph. Eur. Chapter 4.1.1. "Reagents", ref. 1043101).
對于此測試，可以使用與之前測試相同的材料：例如，將氧化鈥 R 的 40 g/L 溶液在含有 141 g/L 高氯酸（HClO4）的高氯酸 R 溶液中制備的高氯酸鈥溶液 R（歐洲藥典第 4.1.1 章 “試劑”，參考文獻 1043101）。

 

If available, the built - in mercury lamp of the instrument may be used for this test. Alternatively, suitable commercial certified filters may be used1.
如果有儀器內(nèi)置的汞燈，可用于此測試。或者，也可使用合適的商業(yè)認證濾光片 1。

 

Method:
方法：

 

Carry out 6 measurements of the absorbance maxima.
對吸光度最大值進行 6 次測量。

 

Limits:
限度：

 

Repeatability: the relative standard deviation of the absorbance maxima should satisfy the manufacturer's specifications.
重復性：吸光度最大值的相對標準偏差應符合制造商的規(guī)格要求。

 

The difference between the 6 individual absorbance maxima values should comply with the manufacturer's specifications (e.g. < 0.5 nm).
6 個單獨的吸光度最大值之間的差值應符合制造商的規(guī)格要求（例如 < 0.5 nm）。

 

4.Baseline Noise

基線噪聲

 

For this test, 2 alternative methods are proposed.
對于此測試，提出了兩種替代方法。

 

TEST 1
測試 1

 

Method:
方法：

Make 61 absorbance measurements with an integration time of 1 second at a wavelength of 500 nm, with no sample in the sample chamber, and calculate the mean.
在 500 納米波長下，積分時間為 1 秒，在樣品室中無樣品的情況下進行 61 次吸光度測量，并計算平均值。

 

Limits:
限度：

Mean ± 0.002 Absorbance units
平均值 ± 0.002 吸光度單位

 

TEST 2
測試 2

 

Method:
方法：

Record the absorbance for 60 seconds at 200, 300 and 400 nm with a highly pure, synthetic Quartz block¹. The measurement is made against air.
使用高純度合成石英塊在 200、300 和 400 納米處記錄 60 秒的吸光度。測量以空氣為參比。

 

Note: If commercial filters are used, the wavelengths and the exact absorption values with the corresponding tolerance limits will depend on the type of filters.
注意：如果使用商用濾光片，波長以及確切的吸收值和相應的容差限度將取決于濾光片的類型。

 

Example of limits:
限度示例：

EDQM發(fā)布《紫外-可見分光光度計確認指南》

 

Photometric Drift
光度漂移

 

Photometric drift should be checked at both the visible and UV region, at appropriate wavelengths. The limits are in accordance with the user's requirements (as defined in Level I) and with manufacturer's specifications.
光度漂移應在可見光和紫外光區(qū)域的適當波長下進行檢查。其限度應符合用戶要求（如一級所定義）和制造商的規(guī)格。

 

For this test, 2 alternative examples are proposed.
對于此測試，提出了兩個替代示例。

 

TEST 1
測試 1

 

Method:
方法：

 

As routine test, the drift is measured at 250 nm over a period of 2 hours by using the Time Scan mode of the instrument, with no sample in the sample chamber.
作為常規(guī)測試，在樣品室無樣品的情況下，使用儀器的時間掃描模式在 250 納米波長下測量 2 小時內(nèi)的漂移。

 

Limits: ± 0.001 Absorbance units/h
限度：±0.001 吸光度單位 / 小時

 

Note: In certain cases, for example when several samples are measured over a long period of time (or when using auto sampler), the drift can also be determined at the wavelength reported in the analytical method, under the same operational conditions, before testing samples.
注意：在某些情況下，例如在長時間測量多個樣品時（或使用自動進樣器時），也可以在測試樣品之前，在相同操作條件下，在分析方法中報告的波長處測定漂移。

 

TEST 2
測試 2

 

Method.
方法

 

Record the baseline for 60 minutes at 500 nm and compare the absorbance with the initial value.
在 500 納米處記錄 60 分鐘基線，并將吸光度與初始值進行比較。

 

Limits: ± 0.002 Absorbance units/h
限度：±0.002 吸光度單位 / 小時

 

Level IV. In - use instrument checks
IV 級 使用中儀器檢查

 

This Annex contains practical examples of tests and their associated acceptance limits for several parameters related to the performance of an UV - Visible spectrophotometer. These examples can be considered by the OMCLs as possible approaches to perform the Level IV of the equipment qualification process: “In - use instrument checks”.
本附錄包含了與紫外 - 可見分光光度計性能相關的幾個參數(shù)的測試實例及其相關的可接受限度。這些實例可被官方藥品控制實驗室（OMCLs）視為執(zhí)行設備確認過程 IV 級 “使用中儀器檢查” 的可行方法。

 

SYSTEM SUITABILITY TEST OF THE METHOD
方法的系統(tǒng)適用性測試

 

REPEATABILITY (for quantitative analysis)

重復性（用于定量分析）

RESOLUTION (for both qualitative and quantitative analysis)

分辨率（用于定性和定量分析）

 

Method:
方法：

 

This test should be performed according to Ph. Eur., the MAH dossier or a suitably validated in - house method.
此測試應根據(jù)《歐洲藥典》、上市許可持有人（MAH）檔案或經(jīng)過適當驗證的內(nèi)部方法進行。

 

 

 

 

 

本文由廣州佳譽醫(yī)療器械有限公司/佛山浩揚醫(yī)療器械有限公司聯(lián)合編輯