USP1058分析儀器的確認

1、分析儀器的確認(USP39-NF34 Page1055)INTRODUCTION'SA large variety of laboratory equipment, instruments, and computerized analytical systems, ranging from simple nitrogen evaporators to complex multiple-function technologies (see Instrument Categories ), are used in the pharmaceutical industry to acquire

2、 data to help ensure that products are suitable for their intended use. An analyst's objective is to consistently obtain reliable and valid data suitable for the intended purpose. Depending on the applications, users validate their procedures, calibrate their instruments, and perform additional

3、instrument checks, such as system suitability tests and analysis of in-process quality control check samples to help ensure that the acquired data are reliable. With the increasing sophistication and automation of analytical instruments, an increasing demand has been placed on users to qualify their

4、 instruments.各種各樣的實驗室設備、儀器、 計算機化分析系統(tǒng)，從簡單的氮吹儀到復雜的多功能技術(見Instrument Categories )，均被用于制藥行業(yè)，以獲得數(shù)據(jù)來確保產(chǎn)品達到預期用途。分析的目的是持續(xù)獲得符合預期目的的可靠的有效數(shù)據(jù)。基于實際應用，使用者進行工藝驗證、儀器校準，并進行額外的儀器檢核，如系統(tǒng)適用性試驗和中間質量控制分析檢查樣品，以確保所獲得數(shù)據(jù)的可靠性。隨著分析儀器的日益復雜化和自動化，對儀器確認的要求也在不斷增加。Unlike method validation and system suitability activities, analytical

5、 instrument qualification (AIQ) currently has no specific guidance or procedures. Competing opinions exist regarding instrument qualification and validation procedures and the roles and responsibilities of those who perform them. Consequently, various approaches have been used for instrument qualifi

6、cation, approaches that require varying amounts of resources and generate widely differing amounts of documentation. This chapter provides a scientific approach to AIQ and considers AIQ as one of the major components required for generating reliable and consistent data. Note that the amount of rigor

7、 applied to the qualification process will depend on the complexity and intended use of the instrumentation.This approach emphasizes AIQ's place in the overall process of obtaining reliable data from analytical instruments.不同于方法學驗證和系統(tǒng)適用性試驗，分析儀器確認（AIQ）目前并沒有明確的 指導和規(guī)程。關于儀器確認和驗證程序，以及執(zhí)行它們的角色和職責，存在著互

8、相矛盾的觀點。由此導致，已有多種方法應用于儀器確認，而這些方法需要使用 的資源數(shù)量各異并產(chǎn)生數(shù)量差異巨大的文件。本節(jié)為分析儀器確認（AIQ）提供了科學的方法，并將分析儀器確認（AIQ）作為產(chǎn)生可靠性和一致性數(shù)據(jù)的重要 組成部分。注意，精確應用于確認工序的程度取決于儀器的復雜程度和預期用途。這種方法強調(diào)了 AIQ從分析儀器中獲得可靠數(shù)據(jù)的全過程中的地位。Validation versus Qualification 驗證 vs 確認In this chapter, the term validation is used for manufacturing processes, analytica

9、l procedures, and software procedures and the term qualification is used for instruments. Thus, the phrase "analytical instrument qualification ” （AIQ） is used for the proce ss of ensuring that an instrument is suitable for its intended application.在本節(jié)中，驗證一詞用于生產(chǎn)工藝、分析方法及軟件程序中，而確認一詞則用于 儀器。因此，”分析儀

10、器的確認” （AIQ）用于確保儀器適用于預期用途的過程。COMPONENTS OF DATA QUALITY 質量的組成There are four critical components involved in the generation of reliable and consistent data （quality data）.Figure 1 shows these components as layered activities within a quality triangle. Each layer adds to the overall quality. Analytical

11、 instrument qualification forms the base for generating quality data. The other components essential for generating quality data are analytical method validation, system suitability tests, and quality control check samples. These quality components are described below.組成可靠和一致數(shù)據(jù)（質量數(shù)據(jù)）的有四個關鍵部分。圖1將這些部分

12、展示在質 量三角形的層級區(qū)域內(nèi)。每層相加構成了整體質量。分析儀器的確認是產(chǎn)生質量 數(shù)據(jù)的基礎。構成質量數(shù)據(jù)的其他部分為分析方法驗證、系統(tǒng)適用性試驗和質量 控制檢驗樣品。這些質量部分詳情如下。Figure 1. Components of data quality.圖1.質量數(shù)據(jù)的組成Analytical Instrument Qualification分析儀器的確認AIQ is the collection of documented evidence that an instrument performs suitably for its intended purpose. Use of a

13、 qualified instrument in analyses contributes to confidence in the validity of generated data.AIQ匯總了為確定儀器符合預期用途的文件證明。使用合格的分析儀器能提高生成數(shù)據(jù)的有效性。Analytical Method Validation 分析方法驗證Analytical method validation is the collection of documented evidence that an analytical procedure is suitable for its intended

14、 use. Use of a validated procedure with qualified analytical instruments provides confidence that the procedure will generate test data ofacceptablequality. Additional guidance on validation of compendial procedures may be found in the general information chapterValidation of CompendialProcedures &l

15、t;1225> .分析方法驗證匯總了分析過程適用于預期用途的文件證明。使用經(jīng)確認的分析儀器和驗證過的方法所產(chǎn)生的測試數(shù)據(jù)才可能符合規(guī)定。 關于藥典中驗證方法的額 外指導可參見通則1225藥典方法的驗證。System Suitability Tests 系統(tǒng)適用性試驗System suitability tests verify that the system will perform in accordance with the criteria set forth in the procedure. These tests are performed along with the sa

16、mple analyses to ensure that the system's performanceis acceptable at the time of the test. USPgeneral chapter Chromatography 621 presents a more detailed discussion of system suitability tests as related to chromatographic systems.系統(tǒng)適用性試驗用于證實該系統(tǒng)符合方法中設定的標準。這些試驗連同樣品分析 一起，確保系統(tǒng)的性能在測試時是適用的。 USP通則621

17、泡譜法呈現(xiàn)了對色譜 系統(tǒng)適用性試驗更詳細的討論。Quality Control Check Samples質量控制檢查樣品Many analysts carry out their tests on instruments standardized using reference materials and/or calibration standards. Some analyses also require the inclusion of quality control check samples to provide an in-process or ongoing assurance

18、 of the test's suitable performance. In this manner, AIQ and analytical method validation contribute to the quality of analysis before analysts conduct the tests. System suitability tests and quality control checks help ensure the quality of analytical results immediately before or during sample

19、 analysis.許多分析員用經(jīng)標準物質和/或校準標準品校準后的儀器進行測試。有些分析員 還要求添加質量控制檢查樣品來保證試驗過程中或持續(xù)的試驗適用性。通過這種方式，AIQ和分析方法驗證在測試前提高了分析的質量。系統(tǒng)適用性試驗和質量 控制檢查則在樣品分析前或過程中確保了分析結果的質量ANALYTICAL INSTRUMENT QUALIFICATION PROCESS分析儀器確認程序The following sections address in detail the AIQ process. The other three components of building quality i

20、nto analytical dataanalytical methodvalidation, system suitability tests, and quality control check samplesare not within the scope of this chapter.下面將詳述AIQ過程。組成分析數(shù)據(jù)質量的另三種成分，分析方法驗證、系統(tǒng)適用性試驗、質量控制檢查樣品，不在此范圍內(nèi)。Qualification Phases確認階段Instrument qualification is not a single continuous process, but instea

21、d results from several discrete activities. For convenience, these activities can be grouped into four phases: design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).儀器確認并非一個單獨連續(xù)的過程， 而是若干個獨立處理的結果。方便起見，這 些處理可分為四個階段：設計確認(DQ、安裝確認(I

22、Q)、運行確認(OQ、 性能確認(PQ 。SomeAIQ activities cover more than one qualification phase, and analysts potentially could perform them during more than one of the phases (see Table 1 ). However, in many instances there is need for specific order to the AIQ activities; for example, installation qualification m

23、ust occur first in order to initiate other qualification activities. The AIQ activities will be defined and documented.一些AIQ涵蓋多個確認階段，分析員傾向于進行多個階段的確認(見表 1)。然 而，在很多情況下，AIQ有特定順序要求；比如，必須先進行安裝確認才能開始 實施其它確認。AIQ將被定義并以文件形式記錄。Table 1. Timing, Applicability, and Activities for Each Phase of*Analytical Instrum

24、ent Qualification -表1.分析儀器確認每一階段的時間表、適用性和活動DesignQualification設計確認InstallationQualification安裝確認OperationalQualificati on運行確認PerformanceQualification性能確認Timing and Applicability時間表和適用性Prior to purchase of a new model of instrument購買儀器之前At installation ofeach instrument(new, old, orexistingunqualified

25、)安裝儀器時(新的、舊 的或一直未經(jīng)確認的)Afterinstallationor major repair of eachinstrument安裝完成后或大修之后Periodically at specified intervals for each instrument 儀器在規(guī)定間隔內(nèi)定期進行Activities 活動Assurance of manufacturer'sDQ保證制造商設計確認Description描述Fixedparameters固定參數(shù)Preventive maintenance and repairs 預防性維護Assurance ofadequate su

26、pportavailabilityfrommanufacturerInstrument delivery儀器運送Establish practices to address operation, calibration, maintenance, and change controlDesignQualification設計確認InstallationQualification安裝確認OperationalQualificati on運行確認PerformanceQualification性能確認保證制造商給予充分支持建立相關規(guī)程用以處理操作、校準、維護及變更控制Instrument'

27、sfitness for usein laboratory儀器在實驗室使用的適用性Utilities/facility公用設施/設備Environment 環(huán)境Assembly andinstallation 組裝與安裝Network and datastorage網(wǎng)絡和數(shù)據(jù)儲存Secure data storage, backup, and archive安全數(shù)據(jù)儲存、備 份與存檔Installationverification安裝確認Instrumentfunction tests儀器性能測試Performance checks性能檢查*_Activities under each pha

28、se are usually performed as given in the table. However, insome cases, it may be more appropriate to perform or combine a given activity with anotherphase. Such activities spanning more than one qualification phase are shown as connectedby double arrows. If an activity listed under a given phase is

29、performed under anotherphase, it is not necessary to repeat the activity under the phase where the activity isDesignQualification設計確認InstallationQualification安裝確認OperationalQualification運行確認PerformanceQualification性能確認listed. Performing the activity is far more important than the phase under which t

30、he activity is performed.每個階段的活動通常按表中所列進行。但在某些情況下，某個活動可能更適合采用另一階段或 者與之結合來進行確認。這些活動橫跨不只一個階段，如表中雙箭頭所示。如果某個列于給定階段 下的活動在另一階段中完成，那么就沒有必要在列出該活動的階段重復進行。完成該項活動比該活 動處于哪個階段重要得多。DESIGN QUALIFICATIO般計確認Design qualification (DQ) is the documented collection of activities that define the functional and operationa

31、l specifications of the instrument and criteria for selection of the vendor, based on the intended purpose of the instrument. Design qualification (DQ) may be performed not only by the instrument developer or manufacturer but also may be performed by the user. The manufacturer is generally responsib

32、le for robust design and maintaining information describing how the analytical instrument is manufactured (design specifications, functional requirements, etc.) and tested before shipment to users. Nonetheless, the user should ensure that commercial off-the-shelf (COTS) instruments are suitable for

33、their intended application and that the manufacturer has adopted a quality system that provides for reliable equipment. Users should also determine the manufacturer's capability for support installation, services, and training. This determination might be aided by the user's previousinteract

34、ion with the manufacturer.設計確認 （ DQ） 是基于儀器的預定用途，對儀器的功能與操作規(guī)程和供應商的選擇標準作出規(guī)定，并以文件記錄。設計確認（DQ不僅可以由儀器開發(fā)者和制造商進行， 也可由使用者進行。制造商通常負責穩(wěn)健設計和維護信息描述分析儀器如何制造（設計規(guī)范、功能要求等），及發(fā)貨前的測試。盡管如此，使用者仍應確保商用成品儀器適用于其預期用途，并且制造商已經(jīng)采納了能提供可靠儀器的質量系統(tǒng)。使用者還應確定制造商有支持安裝、服務、培訓的能力。這個決定可以借助使用者之前與制造商之間的交流完成。INSTALLATION QUALIFICATIO畋裝確認Installati

35、on qualification （IQ） is the documented collection of activities necessary to establish that an instrument is delivered as designed and specified, and is properly installed in the selected environment, and that this environment is suitable for the instrument.IQ applies to an instrument that is new o

36、r was pre-owned, or to any instrument that exists on site but has not been previously qualified.Relevant parts of IQ would also apply to a qualified instrument that has been transported to another location or is being reinstalled for other reasons, such as prolonged storage. The activities and docum

37、entation typically associated with IQ are as follows.安裝確認 （ IQ） 是用于確定儀器是否按照設計和指定的方式運輸并正確安裝在選定的環(huán)境中，以及該環(huán)境對此儀器的適用性，并以文件記錄。IQ 可用于新的或二手的儀器，也可用于已在現(xiàn)場但未經(jīng)確認過的儀器。IQ 的相關部分也可用于某個已經(jīng)確認但又運送至另一場所的儀器，或因其他原因（如長期儲存）需重新安裝的儀器。相關的典型活動和文件如下：Description Provide a description of the instrument or the collectionof instrument

38、 components, including its manufacturer, model, serial number, software version, and location.Use drawings and flow charts whereappropriate.描述提供該儀器或儀器組成部分的描述，包括其制造商、型號、編號、軟件版 本和位置。適當情況下可使用圖紙和流程圖。 Instrument Delivery Ensure that the instrument, software, manuals, supplies, and any other instrument ac

39、cessories arrive as specified in the purchase order and that they are undamaged. For a pre-owned or existing instrument, manuals and documentation should be obtained.儀器運輸確保儀器、軟件、 手冊、 物料和其他儀器附件按照采購單中規(guī)定的方式到達，并且未經(jīng)損壞。對于二手或已有儀器，需要獲得手冊和記錄文件。 Utilities/Facility/Environment Verify that the installation site

40、 satisfactorily meets manufacturer-specified environmental requirements. 公用設備 /設施 /環(huán)境確認安裝場所符合制造商規(guī)定環(huán)境的要求。Assembly and Installation Assemble and install the instrument, and perform any preliminary diagnostics and testing. Assembly and installation may be done by the manufacturer, vendor, specialized e

41、ngineers, or qualified in-house personnel. Manufacturer-established installation tests and guides provide a valuable baseline reference for determining instrument acceptance. Any abnormal event observed during assembly and installation merits documenting. Installation packages purchased from the man

42、ufacturer or the vendor may, however, need to be supplemented with user-specific criteria.組裝和安裝組裝和安裝儀器，并進行預診斷和測試。組裝和安裝可由制造商、供應商、 專業(yè)工程師或經(jīng)授權的內(nèi)部人員來進行。制造商建立的儀器測試和指導為確定儀器的驗收提供了有價值的基本參考。在組裝和安裝過程中任何異常事件均需記錄。但是， 從制造商或供應商處購買的安裝包需要根據(jù)用戶的特定標準進行增補。Network and Data Storage Some analytical systems require users to

43、 provide network connections and data storage capabilities at theinstallation site. Whenrequired, connect the instrument to the network,and check its functionality.網(wǎng)絡和數(shù)據(jù)保存一一些分析系統(tǒng)要求使用者在安裝場所提供聯(lián)網(wǎng)和數(shù)據(jù)儲存功 能。需要時對儀器連網(wǎng)，并檢查其功能。Installation Verification Perform the initial diagnostics and testing of the instru

44、ment after installation.安裝確認一安裝后進行儀器的初始診斷和測試。OPERATIONAL QUALIFICATION 行確認After a successful IQ, the instrument is ready for OQesting. Operational qualification (OQ) is the documented collection of activities necessary to demonstrate that an instrument will function according to its operational spec

45、ification in the selected environment. Testing activities in the OQ phase may consist of these test parameters.IQ成功后，儀器即可進行OQ1認。運彳T確認(OQ是證實儀器具有在選定環(huán)境 中按照其操作規(guī)范運行的功能。OQt段的測試包含了這些測試參數(shù)。Fixed Parameters These tests measure the instrument's nonchanging parameters such as length, height, weight, voltage

46、 inputs, acceptable pressures, and loads. If the manufacturer-supplied specifications for these parameters satisfy the user, the test requirements may be waived.However, if the user wants to confirm the parameters, testing can be performed at the user's site. Fixed parameters do not change over

47、the life of the instrument, and therefore never need redetermination. NOTEThese tests could also be performed during the IQ phase (seeTable 1 );if so, fixed parameters need not be redetermined as part of OQtesting. 固定參數(shù)一這些測試測量儀器的不變參數(shù)，如長度、高度、重量、輸入電壓、可 接受壓力和負荷。如果制造商提供的這些參數(shù)規(guī)格符合用戶要求，就可以免除測 試。但用戶如果需要確認這些

48、參數(shù)，可以在用戶的場地進行測試。固定參數(shù)在儀器壽命周期內(nèi)保持不變，因此無需重測。注：這些測試也可在IQ階段進行（見 表1）;如此一來，固定參數(shù)就無需在OQM試部分重測。Secure Data Storage, Backup, and Archiving Whenapplicable, test secure data handling such as storage, backup, audit trails, and archiving at the user's site according to written procedures.安全數(shù)據(jù)儲存、備份和歸檔當適用時，可根據(jù)書面程

49、序在用戶場所進行測試安全數(shù)據(jù)的處理，如保存、備份、審計追蹤和歸檔。Instrument Function Tests Instrument functions required by the user should be tested to verify that the instrument operates as intended bythe manufacturer. Manufacturer-supplied information is useful in identifying specifications for these parameters and in designing

50、 teststo evaluate the identified parameters. Users, or their qualified designees, should perform these tests to verify that the instrument meets manufacturer or user specifications in the user's environment.儀器功能測試根據(jù)用戶需要對儀器功能進行測試，確認儀器能夠按制造商的預期運行。 制造商提供的信息有助于識別這些參數(shù)的規(guī)格和設計被識別參數(shù)的評估測試。 使用者或授權的指定人員應進行這

51、些測試，以確定在使用環(huán)境中這些儀器滿足制造商或使用者的標準。The extent of OQ testing that an instrument undergoes depends on its intended applications. Therefore, no specific OQtests for any instrument or application are offered in this chapter.儀器OQW試的范圍取決于其預期的用途。因此，在此通則中沒有為任何儀器或 用途提供具體的OQM試。Routine analytical tests do not const

52、itute OQ testing. OQ tests are specifically designed to verify the instrument's operation according to specifications in the user's environment, and repeating the testing at regular intervals may not be required. However, when theinstrumentundergoes major repairs or modifications, relevant O

53、Q and/or PQ testsshould be repeated to verify whether the instrument continues to operatesatisfactorily. If an instrument is moved to another location, an assessment should be made of what, if any, OQ test should be repeated.日常分析測試并不包含OQMtOQW試是特定設計的，用于確認儀器在用戶環(huán)境中根據(jù)規(guī)程的運行情況，并且無需重復測試。然而， 當儀器進行大修或變動時，相關的

54、OCff口/或PQ測試需要重復進行，以確認儀器仍然能很好地運行。如果儀 器移到另一位置，則需要評估哪些 OQM試需重復進行（如果有的話）。OQ tests can be modular or holistic. Modular testing of individual components of a system may facilitate interchanging of such components without requalification. Holistic tests, which involve the entire system, are also acceptable

55、.OQ測試可以模塊化或整體化。系統(tǒng)的單獨部分的模塊測試可以方便這樣的部分 進行交換而無需重新確認。包含全部系統(tǒng)的整體測試也可以接受。PERFORMANCE QUALIFICATION確認Performance qualification （PQ） is the documented collection of activities necessary to demonstrate that an instrument consistently performs according to the specifications defined by the user, and is appropr

56、iate for the intended use. After IQ and OQhave been performed, the instrument's continued suitability for its intended use is demonstrated through performance qualification. The PQ phase may include the following parameters.性能確認（PQ用于證實儀器始終按照使用者的規(guī)范運行，并符合預期用途。IQ和OQ完成之后，通過PQ確認來證實儀器對其預期用途的持續(xù)適用性。PQ階段

57、 包括以下參數(shù)。Performance Checks Set up a test or series of tests to verify the acceptable performance of the instrument for its intended use. PQ testsare usually based on the instrument's typical on-site applications and may consist of analyzing known components or standards. The tests should be base

58、d on good science and reflect the general intended use of the instrument. Somesystem suitability tests or quality control checks that are performed concurrently with the test samples can be used to demonstrate that the instrument is performing suitably. PQ tests may resemble those performed during OQ, but the specifications for theirresults may be set differe