USP1058分析仪器的确认.doc

ANALYTICAL INSTRUMENT QUALIFICATION分析仪器的确认(USP39-NF34 Page1055)INTRODUCTION 介绍A 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 data to help ensure that products are suitable for their intended use. An analysts 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 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 instruments.各种各样的实验室设备、仪器、计算机化分析系统，从简单的氮吹仪到复杂的多功能技术（见Instrument Categories），均被用于制药行业，以获得数据来确保产品达到预期用途。分析的目的是持续获得符合预期目的的可靠的有效数据。基于实际应用，使用者进行工艺验证、仪器校准，并进行额外的仪器检核，如系统适用性试验和中间质量控制分析检查样品，以确保所获得数据的可靠性。随着分析仪器的日益复杂化和自动化，对仪器确认的要求也在不断增加。Unlike method validation and system suitability activities, analytical 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 qualification, 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 applied to the qualification process will depend on the complexity and intended use of the instrumentation. This approach emphasizes AIQs place in the overall process of obtaining reliable data from analytical instruments.不同于方法学验证和系统适用性试验，分析仪器确认（AIQ）目前并没有明确的指导和规程。关于仪器确认和验证程序，以及执行它们的角色和职责，存在着互相矛盾的观点。由此导致，已有多种方法应用于仪器确认，而这些方法需要使用的资源数量各异并产生数量差异巨大的文件。本节为分析仪器确认（AIQ）提供了科学的方法，并将分析仪器确认（AIQ）作为产生可靠性和一致性数据的重要组成部分。注意，精确应用于确认工序的程度取决于仪器的复杂程度和预期用途。这种方法强调了AIQ从分析仪器中获得可靠数据的全过程中的地位。Validation versus Qualification 验证vs确认In this chapter, the term validation is used for manufacturing processes, analytical procedures, and software procedures and the term qualification is used for instruments. Thus, the phrase “analytical instrument qualification” (AIQ) is used for the process of ensuring that an instrument is suitable for its intended application.在本节中，验证一词用于生产工艺、分析方法及软件程序中，而确认一词则用于仪器。因此，“分析仪器的确认”（AIQ）用于确保仪器适用于预期用途的过程。COMPONENTS OF DATA QUALITY 数据质量的组成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 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. 组成可靠和一致数据（质量数据）的有四个关键部分。图1将这些部分展示在质量三角形的层级区域内。每层相加构成了整体质量。分析仪器的确认是产生质量数据的基础。构成质量数据的其他部分为分析方法验证、系统适用性试验和质量控制检验样品。这些质量部分详情如下。Figure 1. Components of data quality.图1.质量数据的组成Analytical Instrument Qualification 分析仪器的确认AIQ is the collection of documented evidence that an instrument performs suitably for its intended purpose. Use of a qualified instrument in analyses contributes to confidence in the validity of generated data.AIQ汇总了为确定仪器符合预期用途的文件证明。使用合格的分析仪器能提高生成数据的有效性。Analytical Method Validation 分析方法验证Analytical method validation is the collection of documented evidence that an analytical procedure is suitable for its intended use. Use of a validated procedure with qualified analytical instruments provides confidence that the procedure will generate test data of acceptable quality. Additional guidance on validation of compendial procedures may be found in the general information chapter Validation of Compendial Procedures . 分析方法验证汇总了分析过程适用于预期用途的文件证明。使用经确认的分析仪器和验证过的方法所产生的测试数据才可能符合规定。关于药典中验证方法的额外指导可参见通则药典方法的验证。System Suitability Tests 系统适用性试验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 sample analyses to ensure that the systems performance is acceptable at the time of the test. USP general chapter Chromatography presents a more detailed discussion of system suitability tests as related to chromatographic systems.系统适用性试验用于证实该系统符合方法中设定的标准。这些试验连同样品分析一起，确保系统的性能在测试时是适用的。USP通则色谱法呈现了对色谱系统适用性试验更详细的讨论。Quality Control Check Samples 质量控制检查样品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 of the tests 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 analysis.许多分析员用经标准物质和/或校准标准品校准后的仪器进行测试。有些分析员还要求添加质量控制检查样品来保证试验过程中或持续的试验适用性。通过这种方式，AIQ和分析方法验证在测试前提高了分析的质量。系统适用性试验和质量控制检查则在样品分析前或过程中确保了分析结果的质量ANALYTICAL INSTRUMENT QUALIFICATION PROCESS分析仪器确认程序The following sections address in detail the AIQ process. The other three components of building quality into analytical dataanalytical method validation, system suitability tests, and quality control check samplesare not within the scope of this chapter.下面将详述AIQ过程。组成分析数据质量的另三种成分，分析方法验证、系统适用性试验、质量控制检查样品，不在此范围内。Qualification Phases 确认阶段Instrument qualification is not a single continuous process, but instead 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).仪器确认并非一个单独连续的过程，而是若干个独立处理的结果。方便起见，这些处理可分为四个阶段：设计确认（DQ）、安装确认（IQ）、运行确认（OQ）、性能确认（PQ）。Some AIQ 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 must occur first in order to initiate other qualification activities. The AIQ activities will be defined and documented. 一些AIQ涵盖多个确认阶段，分析员倾向于进行多个阶段的确认（见表1）。然而，在很多情况下，AIQ有特定顺序要求；比如，必须先进行安装确认才能开始实施其它确认。AIQ将被定义并以文件形式记录。Table 1. Timing, Applicability, and Activities for Each Phase of Analytical Instrument Qualification*表1.分析仪器确认每一阶段的时间表、适用性和活动Design Qualification设计确认Installation Qualification安装确认Operational Qualification运行确认Performance Qualification性能确认Timing and Applicability时间表和适用性Prior to purchase of a new model of instrument购买仪器之前At installation of each instrument (new, old, or existing unqualified)安装仪器时（新的、旧的或一直未经确认的）After installation or major repair of each instrument安装完成后或大修之后Periodically at specified intervals for each instrument仪器在规定间隔内定期进行Activities活动Assurance of manufacturers DQ保证制造商设计确认Description描述Fixed parameters固定参数Preventive maintenance and repairs预防性维护Assurance of adequate support availability from manufacturer保证制造商给予充分支持Instrument delivery仪器运送Establish practices to address operation, calibration, maintenance, and change control建立相关规程用以处理操作、校准、维护及变更控制Instruments fitness for use in laboratory仪器在实验室使用的适用性Utilities/facility 公用设施/设备Environment环境Assembly and installation组装与安装Network and data storage网络和数据储存Secure data storage, backup, and archive安全数据储存、备份与存档Installation verification安装确认Instrument function tests仪器性能测试Performance checks性能检查* Activities under each phase are usually performed as given in the table. However, in some cases, it may be more appropriate to perform or combine a given activity with another phase. Such activities spanning more than one qualification phase are shown as connected by double arrows. If an activity listed under a given phase is performed under another phase, it is not necessary to repeat the activity under the phase where the activity is listed. Performing the activity is far more important than the phase under which the activity is performed.* 每个阶段的活动通常按表中所列进行。但在某些情况下，某个活动可能更适合采用另一阶段或者与之结合来进行确认。这些活动横跨不只一个阶段，如表中双箭头所示。如果某个列于给定阶段下的活动在另一阶段中完成，那么就没有必要在列出该活动的阶段重复进行。完成该项活动比该活动处于哪个阶段重要得多。DESIGN QUALIFICATION 设计确认Design qualification (DQ) is the documented collection of activities that define the functional and operational 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 responsible 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 their intended application and that the manufacturer has adopted a quality system that provides for reliable equipment. Users should also determine the manufacturers capability for support installation, services, and training. This determination might be aided by the users previous interaction with the manufacturer.设计确认（DQ）是基于仪器的预定用途，对仪器的功能与操作规程和供应商的选择标准作出规定，并以文件记录。设计确认（DQ）不仅可以由仪器开发者和制造商进行，也可由使用者进行。制造商通常负责稳健设计和维护信息描述分析仪器如何制造（设计规范、功能要求等），及发货前的测试。尽管如此，使用者仍应确保商用成品仪器适用于其预期用途，并且制造商已经采纳了能提供可靠仪器的质量系统。使用者还应确定制造商有支持安装、服务、培训的能力。这个决定可以借助使用者之前与制造商之间的交流完成。INSTALLATION QUALIFICATION 安装确认Installation 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 or 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 documentation typically associated with IQ are as follows.安装确认（IQ）是用于确定仪器是否按照设计和指定的方式运输并正确安装在选定的环境中，以及该环境对此仪器的适用性，并以文件记录。IQ可用于新的或二手的仪器，也可用于已在现场但未经确认过的仪器。IQ的相关部分也可用于某个已经确认但又运送至另一场所的仪器，或因其他原因（如长期储存）需重新安装的仪器。相关的典型活动和文件如下：Description Provide a description of the instrument or the collection of instrument components, including its manufacturer, model, serial number, software version, and location. Use drawings and flow charts where appropriate. 描述提供该仪器或仪器组成部分的描述，包括其制造商、型号、编号、软件版本和位置。适当情况下可使用图纸和流程图。Instrument Delivery Ensure that the instrument, software, manuals, supplies, and any other instrument accessories 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. 仪器运输确保仪器、软件、手册、物料和其他仪器附件按照采购单中规定的方式到达，并且未经损坏。对于二手或已有仪器，需要获得手册和记录文件。Utilities/Facility/Environment Verify that the installation site satisfactorily meets manufacturer-specified environmental requirements. 公用设备/设施/环境确认安装场所符合制造商规定环境的要求。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 engineers, 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 manufacturer or the vendor may, however, need to be supplemented with user-specific criteria. 组装和安装组装和安装仪器，并进行预诊断和测试。组装和安装可由制造商、供应商、专业工程师或经授权的内部人员来进行。制造商建立的仪器测试和指导为确定仪器的验收提供了有价值的基本参考。在组装和安装过程中任何异常事件均需记录。但是，从制造商或供应商处购买的安装包需要根据用户的特定标准进行增补。Network and Data Storage Some analytical systems require users to provide network connections and data storage capabilities at the installation site. When required, connect the instrument to the network, and check its functionality. 网络和数据保存一些分析系统要求使用者在安装场所提供联网和数据储存功能。需要时对仪器连网，并检查其功能。Installation Verification Perform the initial diagnostics and testing of the instrument after installation. 安装确认安装后进行仪器的初始诊断和测试。OPERATIONAL QUALIFICATION 运行确认After a successful IQ, the instrument is ready for OQ testing. Operational qualification (OQ) is the documented collection of activities necessary to demonstrate that an instrument will function according to its operational specification in the selected environment. Testing activities in the OQ phase may consist of these test parameters.IQ成功后，仪器即可进行OQ确认。运行确认（OQ）是证实仪器具有在选定环境中按照其操作规范运行的功能。OQ阶段的测试包含了这些测试参数。Fixed Parameters These tests measure the instruments nonchanging parameters such as length, height, weight, voltage 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 users site. Fixed parameters do not change over the life of the instrument, and therefore never need redetermination. NOTE These tests could also be performed during the IQ phase (see Table 1); if so, fixed parameters need not be redetermined as part of OQ testing. 固定参数这些测试测量仪器的不变参数，如长度、高度、重量、输入电压、可接受压力和负荷。如果制造商提供的这些参数规格符合用户要求，就可以免除测试。但用户如果需要确认这些参数，可以在用户的场地进行测试。固定参数在仪器寿命周期内保持不变，因此无需重测。注：这些测试也可在IQ阶段进行（见表1）；如此一来，固定参数就无需在OQ测试部分重测。Secure Data Storage, Backup, and Archiving When applicable, test secure data handling such as storage, backup, audit trails, and archiving at the users site according to written procedures. 安全数据储存、备份和归档当适用时，可根据书面程序在用户场所进行测试安全数据的处理，如保存、备份、审计追踪和归档。Instrument Function Tests Instrument functions required by the user should be tested to verify that the instrument operates as intended by the manufacturer. Manufacturer-supplied information is useful in identifying specifications for these parameters and in designing tests to 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 users environment. 仪器功能测试根据用户需要对仪器功能进行测试，确认仪器能够按制造商的预期运行。制造商提供的信息有助于识别这些参数的规格和设计被识别参数的评估测试。使用者或授权的指定人员应进行这些测试，以确定在使用环境中这些仪器满足制造商或使用者的标准。The extent of OQ testing that an instrument undergoes depends on its intended applications. Therefore, no specific OQ tests for any instrument or application are offered in this chapter.仪器OQ测试的范围取决于其预期的用途。因此，在此通则中没有为任何仪器或用途提供具体的OQ测试。Routine analytical tests do not constitute OQ testing. OQ tests are specifically designed to verify the instruments operation according to specifications in the users environment, and repeating the testing at regular intervals may not be required. However, when the instrument undergoes major repairs or modifications, relevant OQ and/or PQ tests should be repeated to verify whether the instrument continues to operate satisfactorily. If an instrument is moved to another location, an assessment should be made of what, if any, OQ test should be repeated.日常分析测试并不包含OQ测试。OQ测试是特定设计的，用于确认仪器在用户环境中根据规程的运行情况，并且无需重复测试。然而，当仪器进行大修或变动时，相关的OQ和/或PQ测试需要重复进行，以确认仪器仍然能很好地运行。如果仪器移到另一位置，则需要评估哪些OQ测试需重复进行（如果有的话）。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.OQ测试可以模块化或整体化。系统的单独部分的模块测试可以方便这样的部分进行交换而无需重新确认。包含全部系统的整体测试也可以接受。PERFORMANCE QUALIFICATION 性能确认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 appropriate for the intended use. After IQ and OQ have been performed, the instruments continued suitability for its intended use is demonstrated through performance qualification. The PQ phase may include the following parameters.性能确认（PQ）用于证实仪器始终按照使用者的规范运行，并符合预期用途。IQ和OQ完成之后，通过PQ确认来证实仪器对其预期用途的持续适用性。PQ阶段包括以下参数。Performance Checks Set up a test or series of tests to verify the acceptable performance of the instrument for its intended use. PQ tests are usually based on the instruments typical on-site applications and may consist of analyzing known components or standards. The tests should be based on good science and reflect the general intended use of the instrument. Some system 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 their results may be set differently if required. Nevertheless, user specifications for PQ tests should demonstrate trouble-free instrument operation for the intended applications. As is the case with OQ testing, PQ tests may be modular or holistic. 性能检查设立一个或一系列测试来确认仪器具有满足其预期用途的性能。PQ测试通常基于仪器典型的现场应用，并且可以包含分析已知组分或标准物。测试应具备良好的科学基础并反应该仪器的一般预期用途。与试样同时进行的一些系统适用性测试或质量控制检查可用于证明仪器可适当地运行。PQ与OQ测试可能相同，但其结果的标准设定根据需要可以不同。尽管如此，用户标准的PQ测试应确定仪器在预期用途上的无故障运行。同OQ测试一样，PQ测试也可模块化或整体化。Testing frequency depe