USP <1058> 分析仪器的确认（转载中英文）

巴西木

【转载】USP <1058> 分析仪器的确认（转载中英文）  

非常感谢：Julia

<1058> ANALYTICAL INSTRUMENT QUALIFICATION

分析仪器的确认

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 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 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.

极其多种多样的实验室设备、仪器、计算机分析系统，从简单的氮吹仪到复杂的多功能技术（见仪器种类），被应用于制药工业，以取得数据来确保产品适合其预定用途。分析员的目标是持续地获得适合其意图的可靠和有效的数据。取决于具体的应用，使用者验证其方法、校准其仪器，并进行额外的仪器检查，例如系统适用性测试和中间质量控制检查样品的分析，以便帮助确保所获得的数据是可靠的。随着分析仪器的复杂性和自动化程度不断增加，使用者已经感受到了不断增加的确认其仪器的要求。

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 amount 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 AIQ’s place in the overall process of obtaining the reliable data from analytical instruments.

不同于验证和系统适用性工作，分析仪器的确认（AIQ）目前尚没有具体的指导方针或程序。关于仪器确认和验证程序，以及这些程序的执行者的角色和职责，存在着相互冲突的多种观点。由此导致，多种方法已经应用于仪器确认，而这些方法要求使用的资源数量各异并产生数量差距很大的文档。此通则为AIQ提供了科学的方法，并将AIQ视为产生可靠和一致的数据所必需的主要组成部分之一。注意，应用到确认过程的严格程度将由该仪器的复杂性和预定用途来决定。这个方法强调了AIQ在从分析仪器中获得可靠数据的全过程中的位置。

Validation versus Qualification    验证对确认

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.

在此通则中，验证一词用于生产工艺、分析方法、软件程序，而确认一词用于仪器。因此，“分析仪器的确认”（AIQ）一词用于确保仪器适用于其预定用途的过程。

COMPONENTS OF DATA QUALITY   数据质量的组成部分

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 checks samples. These quality components are described as below.

在产生可靠和一致的数据（质量数据）的过程中涉及了四个重要的组成部分。图1以层叠形式在质量三角形内展示了这些组成部分。每层相加构成了总体质量。分析仪器确认构成了产生质量数据的基础。作为质量数据产生的基础的其他组成部分为分析方法验证、系统适用性测试、质量控制检验样品。这些质量部分描述如下。

Analytical Instrument Qualification    分析仪器确认

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是证明某个仪器表现得适合其预定用途的文件证据的汇总。在分析中使用确认过的仪器确保了对所生成数据的有效性的信心。

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 <1225>.

分析方法验证是某个分析方法适合其预定用途的文件证据的汇总。使用确认过的分析仪器和验证过的方法确保了该方法将会产生质量可接受的测试数据的信心。关于药典方法的验证方法的额外指导原则可以在通则药典方法的验证<1225>中找到。

System Suitability Tests系统适用性测试

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 system’s performance is acceptable at the time of the test. USP general chapter Chromatography <621> presents a more detailed discussion of system suitability tests as related to chromatographic systems.

系统适用性测试证实该系统的表现将会符合此方法中设定的标准。这些测试与样品分析仪器进行，从而确保此系统的表现在测试的时候是可以接受的。USP通则色谱法<621>呈现了对于色谱系统的系统适用性测试的更加具体讨论。

Quality Control Check Samples    质量控制检验样品

Many analysts carry out their tests on instruments standardized using reference materials and/or calibration standards. Some analysts also require the inclusion of quality control check samples to provide an in-process or ongoing assurance 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 analysis.

许多分析员在以标准物质和/或校准标准品进行标准化的仪器上进行他们的测试。一些分析员还要求加入质量控制检验样品，以便对此测试的适当表现提供中间或持续的保证。在这个方面，在分析员进行该测试之前，AIQ和分析方法验证就对分析质量起到了作用。系统适用性测试和质量控制检查，则在样品分析马上开始之前或在其过程中，帮助确保分析结果的质量。

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 data ----- analytical method validation, system suitability tests, and quality control check samples ----- are not within the scope of this chapter.

下面的章节具体解答了AIQ的过程。确保分析数据质量的其他3个组成部分，分析方法验证、系统适用性测试、质量控制检验样品，不在此通则的范围之内。

Qualification Phases   确认的阶段

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).

仪器确认不是一个单独的连续过程，而是源自若干独立活动的结果。为方便起见，这些活动可以被归为4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活动包括了超过一个确认阶段，并且分析员倾向于可以跨阶段进行这些活动（见表1）。但是，在很多情况下，AIQ活动有特定的顺序要求；例如，安装确认必须首先发生，以便启动其他确认活动。AIQ活动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*

Design Qualification	Installation Qualification		Operational Qualification		Performance Qualification
	Timing and Applicability
Prior to purchase of a new model of instrument	At installation of each instrument (new, old, or existing unqualified)		After installation or major repair of each instrument		Periodically at specified intervals for each instrument
	Activities
Assurance of manufacturer’s DQ	Description	← →	Fixed parameters		Preventive maintenance and repairs
Assurance of adequate support availability from manufacturer	Instrument delivery				Establish practices to address operation, calibration, maintenance, and change control
Instrument’s fitness for use in laboratory	Utilities/facility	← →	Environment
	Assembly and installation
	Network and data storage	← →	Secure data storage, backup, and archive
	Installation verification	← →	Instrument function tests	← →	Performance checks

*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.

表1. 分析仪器确认每个阶段的时间表、实用性、活动

设计确认	安装确认		运行确认		性能确认
	时间表和实用性
在购买新型仪器之前	在安装每个仪器时(新的、旧的、或一直未经确认的)		在每个仪器安装或大修之后		每个仪器在规定的间隔定期进行
	活动
确认制造商设计确认	描述	← →	固定参数		预防性保养和维修
确认制造商可以给与充分支持	仪器运送				设立相关规程，以解决操作、校准、维护、变更控制
仪器在实验室中使用的适用性	公用设施/设施	← →	环境
	组装与安装
	网络和数据储存	← →	安全的数据储存、备份、存档
	安装确认	← →	仪器功能测试	← →	性能测试

在每个阶段下的活动通常按照表中列出地进行。但是，在某些情况下，可以更加适合进行或合并某个特定活动于其他阶段。这样跨域超过一个确认阶段的活动用双箭头连接来显示。如果某个列出于特定阶段的活动进行于另外一个阶段，没有必要在列出该活动的阶段重复进行。进行该活动要比该活动在那个阶段进行重要许多。

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 the 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) instrument 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 manufacturer’s capability for support installation, services, and training. This determination might be aided by the user’s previous interaction with the manufacturer.

设计确认（DQ）是基于仪器预定用途，对仪器的功能与操作标准和提供商的选取标准做出规定的活动总汇，并以文件记录。设计确认（DQ）不仅可以由仪器开发者或制造商进行，也可以有使用者进行。制造商通常负责稳健设计和维护信息，描述该分析仪器如何制造（设计标准、功能要求等）在发给客户之前如何测试。虽然如此，使用者仍应该确保商用成品仪器适用于他们的预定用途，并且制造商已经采纳了能够保证仪器可靠的质量系统。使用者也应该确定制造商在辅助安装、服务、培训方面的能力。确定的过程可以借助使用者以前与制造商的互动交流。

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 previous 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）是对用于确定某个仪器按照设计和规定的方式运输并正确安装在选定的环境中，以及该环境适合于此仪器所必需的活动总汇，并以文件记录。IQ应用于某件仪器，其可以是新的或是二手的，或应用于任何已经在现场但是此前从未确认过的仪器。IQ的相关部分也会用于某个已经确认的设备，但是该设备经过运输至另外的一个场所或由于其他原因（例如，延长的存储）重新安装。通常与IQ相关的活动和文件如下。

Description----- Provide a description of the instrument or the collection of instrument components, including its manufacturer, model, serial number, software version, and location. Use of drawings and flow chart where appropriate.

描述-----提供该仪器或者仪器组成部分汇总的描述，包括其制造商、型号、编号、软件版本、放置位置。适当情况下使用图纸和流程图。

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----- 确保该仪器、软件、手册、供给品，以及其他仪器附件按照订单中规定的方式抵达，并且他们没有损坏。对于二手或已有的仪器，手册和记录文件必须得到。

Utilities/Facility/Environment----Verify that the installation site satisfactorily meets manufacturer-specified environmental requirements.

公用设施/设施/环境-----证实安装区域令人满意地达到了制造商规定的环境要求。

Assembly and installation---- Assembly 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，并进行任何预诊断和测试。组装和安装可以由其制造商、供应商、专业工程师、或有资质的内部员工来进行。对于确定仪器的验收，制造商确定的安装测试和指导提供了具有价值的基本参考。在组装和安装过程中观察到的任何异常事件均需以文件记录。但是，购自制造商或供应商的安装包需要根据用户的具体标准进行补充。

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.

网络和数据储存----- 一些分析系统要求使用者在安装场所提供网络连接和数据存储能力。当需要时，将仪器连接到网络，并检查其功能。

Installation Verification---- Perform the initial diagnostics and testing of the instrument after installation.

安装认证---- 在安装之后，进行该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 consist of these test parameters.

在成功的IQ之后，此仪器就可以进行OQ测试了。操作确认（OQ）是证实某个仪器将会在选定的环境中按照其操作规范运行所必需的活动总汇，并以文件记录。在OQ阶段的测试活动包含了这些测试参数。

Fixed Parameter---- These tests measure the instrument’s non-changing parameter 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 user’s 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---- 这些测试测量该仪器的不变参数，例如长度、高度、重量、输入电压、可接受压力、载荷等。如果由制造商提供的这些参数的规格令用户满意，可以放弃测试要求。但是，如果用户需要确认这些参数，可以在使用者的场地进行测试。固定参数在仪器的寿命周期内不会变化，并且因此不需重测。【注意：这些测试还可以在IQ阶段（见表1）进行；如果这样，固定参数作为OQ测试的一部分，无需重测。】

Secure Data Storage, Backup, and Archiving---- When applicable, test secure data handling such as storage, backup, audit trails, and archiving at the user’s site according to written procedures.

安全数据存储、备份、存档---- 当可行的时候，根据书面程序，在用户的场所测试安全数据处理工作，例如存储、备份、审计追踪、存档等。

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 user’s environment.

仪器功能测试---- 使用者要求的仪器功能应该被测试，以确认该仪器能够按照制造商所预期地操作。制造商提供的信息有助于识别这些参数的规范，并帮助设计用于评估这些识别出来的参数的测试。使用者，或者他们的有资质的设计师，应该进行这些测试，以便证实该仪器在使用者的环境中达到了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.

某个仪器经历的OQ测试的程度取决于其预定用途。因此，在此通则中没有为任何仪器或用途提供任何具体的OQ测试。

Routine analytical tests do not constitute 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 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.

日常分析检测不构成OQ测试。OQ测试是特别设计，用于确认在用户环境中该仪器根据其规范的运行情况，并且定且重复该测试可能没有必要。但是，当仪器经历大修或改装时，相关的OQ和/或PQ测试应该重复，以便确认该仪器是否继续令人满意地运转。如果某个仪器移到另一个位置，应该进行一项评估，以确定什么OQ测试应该被重复（如果确实有的话）。

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, when involve the entire system, are also acceptable.

OQ测试可以为模块式或整体式。系统中的单个组成部分的模块式测试可以方便这样的组成部分的交换，而无需重新确认。设计整个系统的整体式测试也是可以接受的。

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 instrument’s continued suitability for its intended use is demonstrated through performance qualification. The PQ phase may include the following parameters.

性能确认（PQ）是证实某个仪器持续地按照由用户定义的规范运行，并适合其预定用途的活动总汇，并以文件记录。在IQ和OQ已经执行之后，该仪器对其预定用途的持续适用性通过性能确认来证实。此PQ阶段可以包括下列参数。

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 instrument’s 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，以确认具有满足其预定用途的表现。PQ测试通常基于仪器常见的现场用途并且可以包含分析已知组分或标准物。该测试应该具备良好的科学基础并反映该仪器的一般用途。与供试样品同步进行的一些系统适用性测试或者质量控制检查可以用于证实该仪器正在适当地运行。PQ测试可以模拟在OQ中进行的那些测试，但是如果需要，其结果的质量标准可以设定得不同。尽管如此，使用者对于PQ测试的标准应该证实仪器在其用途上的无故障运行。如同OQ测试一样，PQ测试可以为模块式或整体式。

Testing frequently depends on the ruggedness of the instrument and the criticality of the tests performed. Testing may be unscheduled---- for example, each time the instrument is used. It may be also scheduled for regular intervals. Experience with the instrument can influence this decision. It may be useful to repeat the same PQ tests each time the instrument is used so that a history of the instrument’s performance can be compiled. Alternatively, the instrument may be incorporated into an integrated support system to assure that it remains continually qualified. Some system suitability tests or quality control checks that are performed concurrently with the test samples also imply that the instrument is performing suitably.

测试的频率取决于该仪器的耐用性和利用其所做检验的重要性。测试可以是不定时的---- 例如该仪器每次使用的时候。它也可以在相同间隔下定时进行。使用该仪器的体验可以影响这个决定。最好每次使用仪器时重复同样PQ测试，以便能够汇编该仪器表现的历史数据。两个方法中的另外一个是，该仪器可以整合到一个整体辅助系统，以便确保其持续保持已确认的状态。与供试样品同步进行的一些系统适用性测试或质量控制检查也会说明该仪器正在适当地运行。

Preventive Maintenance and Repairs---- When an instrument fails to meet PQ test specifications, it requires maintenance or repair. A periodic preventive maintenance may also be recommended for many instruments. The relevant PQ test(s) should be repeated after the needed maintenance or repair to ensure that the instrument remains qualified.

预防性维护和修理----当某个仪器未能达到PQ测试标准，则该仪器需要维护或修理。还建议对许多仪器进行定期预防性维护。在需要的维护或修理之后，应该重复相关的一个或多个PQ测试，以确保该仪器保持合格状态。

Practices for Operation, Calibration, Maintenance, and Change Control---- Establish practices to maintain and calibrate the instrument. Each maintenance and calibration activity should be documented.

运行、校准、维护、变更控制的操作规范---- 建立维护和校准仪器的操作规范。每次维护和校准活动均应以文件记录。

ROLES AND RESPONSIBILITIES角色与职责

Users  使用者

Users are ultimately responsible for instrument operations and data quality. The user’s group encompasses analyst, their supervisor, instrument specialists, and organization management. Users should be adequately trained in the instrument’s use, and their training records should be maintained as required by the regulations.

使用者最终负责仪器的操作和数据质量。使用者团队包括分析员、其监督者、仪器专家、机构管理层。使用者应该就仪器使用接受充分的培训，并且他们的培训记录应该按照法规要求进行存档。

Users should also be responsible for qualifying their instruments because their training and expertise in the use of instruments make them the best-qualified group to design the instrument test(s) and specification(s) necessary for successful AIQ. Consultants, equipment manufacturer or vendors, validation specialists, and quality assurance (QA) personnel can advise and assist as needed, but the final responsibility for qualifying instruments lies with the users. The users must also maintain the instrument in a qualified state by routinely performing PQ.

使用者还应该负责确认仪器，因为他们在仪器使用方面接受的培训和专业知识，使得他们成为在设计成功的AIQ所必需的仪器测试和质量标准方面最具资质的团队。顾问、设备制造商或提供商、验证专家、质量保证（QA）人员可以在需要时建议并协助，但是确认仪器的最终责任落在使用者身上。使用者还必须通过进行日常PQ，来使该仪器保持在合格的状态。

Quality Unit质量部门

The role of the Quality Unit in AIQ remains the same as for any other regulated activity. Quality personnel are responsible for assuring that the AIQ process meets compliance requirements, that processes are being followed, and that the intended use of the equipment is supported by valid and documented data.

质量部门在AIQ中的角色与在任何其他监管活动中相同。质量员工负责确保AIQ程序达到符合性要求，程序被遵照执行，并且仪器的预定用途被有效的且以文件记录的数据所支持。

Manufacturers制造商

Manufacturers and developers are responsible for DQ when designing the instrument. They are also responsible for validation of relevant processes used in manufacturing and assembly of the instrument. Manufacturers should test the assembled instruments before shipping them to users.

制造商和开发商负责在设计该仪器时的DQ。他们还要负责对执照和组装该仪器中所用的相关工艺进行验证。在发货给用户之前，制造商应该测试组装好的仪器。

Finally, it is desirable that manufacturers and vendors should notify all known users about hardware defects discovered after a product’s release; offer user training, service, repair, and installation support; and invite user audits as necessary.

最终，最好制造商和供应商应该通知所有已知用户，关于某个产品放行之后发现的硬件缺陷；提供用户培训、服务、修理、安装支持；并在需要时邀请用户进行审计。

SOFTWARE VALIDATION   软件验证

Software used for analytical work can be classified into three categories: firmware; instrument control, data acquisition, and processing software; and stand-alone software. Although software validation is not the primary focus of this chapter, the following sections describe in which cases this activity is under the scope of the analytical instrument qualification.

用于分析工作的软件可以分为三类：固件；仪器控制、数据获取、处理软甲；和独立软件。尽管软件验证不是此通则的主要关注点，下面的部分仍然描述了在什么情况下这些活动处于分析仪器确认的范畴内。

Firmware  固件

Computerized analytical instruments contain integrated chips with low-level software (firmware). Such instruments will not function without properly operating firmware, and users generally cannot alter firmware design or function. Firmware is therefore considered a component of the instrument itself. Indeed, the qualification of hardware is not possible without operating it via its firmware. Thus, when the hardware (that is, the analytical instrument) is qualified at the user’s site, the integrated firmware is also essentially qualified. No separate on-site qualification of the firmware is needed. Whenever possible, the firmware version should be recorded as part of the IQ activities. Any changes made to firmware versions should be tracked through change control of the instrument (see Change Control, below)

计算机化的分析仪器包含带低层次软件（固件）的整合芯片。不正确操作固件，这样的仪器将无法运行，并且使用者通常不能改变固件的设计或功能。固件因此被认为该仪器的一个组成部分。实际上，不通过其固件操作该仪器，硬件的确认就没有可能。因此，当硬件（即分析仪器）在使用者的场所确认时，整合的固件实质上也就确认了。单独的固件现场确认是不需要的。只要可能，无论何时，固件的版本应当被记录为IQ活动的一部分。对固件版本的任何变更都应该通过该仪器的变更控制程序进行追踪（见下面的变更控制）

Instrument Control, Data Acquisition, and Processing Software

仪器控制、数据获取、和处理软件

Software for instrument control, data acquisition, and processing for many of today’s computerized instruments is loaded on a computer connected to the instrument. Operation of the instrument is then controlled via the software, leaving fewer operating controls on the instrument. Also, the software is needed for data acquisition and post-acquisition calculations. Thus, both hardware and software, their functions inextricably intertwined, are critical to providing analytical results.

在今日许多计算机化的仪器中用于仪器控制、数据获取、处理的软件是安装在连接到仪器的电脑上。然后通过该软件操作仪器，在仪器上没有留下什么操作控制。该软件还用于数据获取和获取后的计算。因此，不论软件还是硬件，它们的功能已经纠缠在一起无法分开，对于提供分析结果均非常关键。

The manufacturer should perform DQ, validate this software, and provide users with a summary of validation. At the user site, holistic qualification, which involves the entire instrument and software system, is more efficient than modular validation of the software alone. Thus, the user qualifies the instrument control, data acquisition, and processing software by qualifying the instrument according to the AIQ process.

制造商应该执行DQ，验证此软件，并且为使用者提供一份验证总结。在使用者的场所，整体验证，其涉及整个仪器和软件系统，比软件单独的模块验证更有效率。因此，使用者通过根据AIQ程序确认该仪器的方法，来确认仪器控制、数据获取、和处理软件。

Stand-Alone Software   独立软件

An authoritative guide for validating stand-alone software, such as LIMS, is available.[1] The validation process is administered by the software developer, who also specifies the development model appropriate for the software. Validation takes place in a series of activities planned and executed through various stages of the development cycle.

现在有了用于验证独立软件（例如LIMS）的权威指导方针。验证程序有软件研发者管理，其还详细规定了适合该软件的研发模型。验证发生在通过研发周期的多个阶段来计划与执行的一系列活动中。

CHANG CONTROL变更控制

Changes to instruments, including software, become inevitable as manufacturers add new features and correct known defects. However, implementing all such changes may not always benefit users. Users should therefore adopt changes they deem useful or necessary and should also assess the effects of changes to determine what, if any, requalification is required. The change control process enables them to do this.

当制造商增加新功能并更正已知缺陷，对仪器的变更，包括软件，成为无可避免的事情。但是，落实所有这些变更可能不会总是令使用者获益。因此，使用者应该采纳他们认为有用或必须的变更，并且还应该评价变更的效果，以确定是否需要以及需要什么样的再确认。变更控制程序令他们可以做这些工作。

Change control may follow the DQ/IQ/OQ/PQ classification process. For DQ, evaluate the changed parameters, and determine whether need for the change warrants implementing it. If implementation of the change is needed, install the changes to the system during IQ. Evaluate which of the existing OQ and PQ tests need revision, deletion, or addition, as a result of the installed change. Where the change calls for additions, deletions, or revisions to the OQ or PQ tests, follow the procedure outlined below.

更控制可以遵照DQ/IQ/OQ/PQ分级程序。对于DQ，评价变更的参数，并确定对变更的需要是否能使执行该变更有正当理由。如果该变更的执行是需要的，在IQ过程中对系统执行该变更。评价现存的OQ和PQ测试中那些需要修改、删除、或增加，作为已执行变更的结果。当变更要求对OQ或PQ测试进行增加、删除、或更改时，遵照下面列出的程序。

Operational Qualification---- Revise OQ tests as necessitated by the change. Perform the relevant tests affected by the change. This ensures the instrument’s effective operation after the change is installed.

行确认---- 按照变更所要求的，更改OQ测试。执行受到变更影响的相关测试。这确保了在变更执行之后仪器的有效运行。

Performance Qualification---- Revise PQ tests as necessitated by the change. Perform the PQ testing after installation of the change if similar testing is not already performed during OQ. In the future, perform the revised PQ testing.

能确认---- 按照变更所要求的，更改PQ测试。在变更执行之后，进行PQ测试，如果类似的测试没有在OQ中执行过。在将来，执行更改过的PQ测试。

For changes to firmware and to software for instrument control, data acquisition, and processing, change control is performed through DQ/IQ/OQ/PQ of the affected instrument. Change control for stand-alone software requires user-site testing of the changed functionality.

关于对固件和用于仪器控制、数据获取、和处理的软件的变更，通过对受影响仪器的DQ/IQ/OQ/PQ来进行变更控制。独立软件的变更控制需要被变更功能的使用场所测试。

AIQ DOCUMENTATION  AIQ   记录文件

Documents obtained during instrument qualification should be retained in an accessible manner. Where multiple instruments of one kind exist, documents common to all instruments and documents specific to an instrument may be stored separately. During change control, additional documents may supplement those obtained during the qualification process, and both sets of documents should be retained and maintained in a suitable manner that allows for appropriate protection and access.

在仪器确认过程中得到的文件应该以方便使用的方式进行保存。当一种仪器存在多个时，所有仪器通用的文件和具体对应某个仪器的文件可以分开存放。在变更控制过程中，额外的文件补充到那些在确认过程中所得到的文件中，并且此两套文件应该以适当的方式来保存和维护，以便允许适当的保护和使用。

INSTRUMENT CATEGORIES   仪器种类

Modern laboratories typically include a suite of instruments and equipment varying from simple nitrogen evaporators to complex automated instruments. Therefore, applying a single set of principles to qualifying such dissimilar instruments would be scientifically inappropriate. Users are most capable of establishing the level of qualification needed for an instrument. On the basis of the level needed, it is convenient to categorize instruments into three groups: A, B, and C, as defined below. Examples of instruments in each group are provided. Note that the list of instruments provided here is for illustration only and is not meant to be exhaustive. It does not provide the exact category for an instrument at a user site. That category should be determined by users for their specific instruments or applications.

现代实验室通常包括一套仪器和设备，差异从氮吹仪到复杂的自动仪器。因此，应用单一的一套原则来确认这样不同的仪器将是不科学的。使用者最有能力确立某个仪器所需要的确认程度。基于所需的程度，可以方便地将仪器分为三类：A、B、C，具体定义如下。每类仪器均提供了样板。注意，在此提供的仪器清单仅仅用于举例说明，并不意味着全部仪器。其并未提供在用户场所的某个仪器的准确类别。该类别应该由用户根据他们具体的仪器或用途来确定。

The exact grouping of an instrument must be determined by users for their specific requirements. Depending on individual user requirements, the same instrument may appropriately fall into one group for one user and another group for another user. Therefore, a careful selection of groups by users is highly encouraged.

某个仪器的准确分组必须通过使用者对其的具体要求来确定。取决于具体的用户需求，同样的仪器可以适当地在一个用户处归为一类，而在另一个用户处归为另外一类。因此，强烈鼓励由用户对分类进行仔细选择。

Group A  A类

Group A includes standard equipment with no measurement capability or usual requirement for calibration, where the manufacturer’s specification of basic functionality is accepted as user requirements. Conformance of Group A equipment with user requirements may be verified and documented through visual observation of its operation. Examples of equipment in this group are nitrogen evaporators, magnetic stirrers, vortex mixers, and centrifuges.

类包括没有测量能力或通常的校准要求的标准设备，其中制造商对基本功能的标准被接受为用户需求。A类设备与用户需求的符合性可以通过肉眼观察其操作来确认，并以文件记录。此类设备的样板是氮吹仪、磁力搅拌器、漩涡混合器、和离心机。

Group B   B类

Group B includes standard equipment and instruments providing measured values as well as equipment controlling physical parameters (such as temperature, pressure, or flow) that need calibration, where the user requirements are typically the same as the manufacturer’s specification of functionality and operational limits. Conformance of Group B instruments or equipment to user requirements is determined according to the standard operating procedures for the instrument or equipment, and documented during IQ and OQ. Examples of instruments in this group are balances, melting point apparatus, light microscopes, pH meters, variable pipets, refractometers, thermometers, titrators, and viscosimeters. Examples of equipment in this group are muffle furnaces, ovens, refrigerator-freezers, water baths, pumps, and dilutors.

B类包括提供测量所得数值的标准设备和仪器，以及控制需要校准的物理参数（例如温度、压力、或流动）的设备，其中用户需求通常与制造商的功能标准和操作限度相同。B类仪器或设备对用户需求的符合性是按照该仪器或设备的标准操作程序来测定的，并在IQ和OQ中以文件记录。此类仪器的样板是天平、熔点仪、光学显微镜、酸度计、可变量移液器、折光仪、温度计、滴定仪、黏度计。此类设备的样板是马弗炉、烘箱、冰箱-冰柜、水浴锅、泵、稀释仪。

Group C   C类

Group C includes instruments and computerized analytical systems, where user requirements for functionality, operational, and performance limits are specific for the analytical application. Conformance of Group C instruments to user requirements is determined by specific function tests and performance tests. Installing these instruments can be a complicated undertaking and may require the assistance of specialists. A full qualification process, as outlined in this document, should apply to these instruments. Examples of instruments in this group include the following:

C类包括仪器和计算机化系统，其中对功能、操作、性能限度的用户需求针对特定的分析用途。C类仪器对用户需求的符合性通过具体的功能测试和性能测试来测定。安装这些仪器可以是一项负责的任务，并可能要求专家的协助。应该将在此文件中所描述的完全确认程序应用于这些仪器。此类仪器的样本包括下面这些：

l         atomic absorption spectrometers原子吸收光谱仪

l         differential scanning calorimeters差示扫描量热仪

l         dissolution apparatus溶出度仪

l         electron microscopes电子显微镜

l         flame absorption spectrometers火焰吸收光谱仪

l         high-pressure liquid chromatographs高压液相色谱仪

l         mass spectrometers质谱仪

l         microplate readers酶标仪

l         thermal gravimetric analyzers热重分析仪

l         X-ray fluorescence spectrometers  X射线荧光光谱仪

l         X-ray powder diffractometers   X射线粉末衍射仪

l         densitometers密度计

l         diode-array detectors二极管阵列检测器

l         elemental analyzers元素分析仪

l         gas chromatographs气相色谱仪

l         IR spectrometers红外光谱仪

l         near-IR spectrometers近红外光谱仪

l         Raman spectrometers拉曼光谱仪

l         UV/Vis spectrometers紫外/可见光光谱仪

l         inductively coupled plasma-emission spectrometers电感耦合等离子发射光谱仪

---

[1] General Principle of Software Validation: Final Guidance for Industry and FDA Staff, U.S Department of Health and Human Services, Food and Drug Administration, Rockville, MD, January 11, 2002.http://www.fda.org/cdrh/comp/guidance/938.html (accessed September 2004)软件验证的基本准则：行业与FDA员工的最终指导方针，美国卫生与人类服务部，食品与药品管理局，Rockville，MD，2002年1月11日，网址：http://www.fda.org/cdrh/comp/guidance/938.html （2004年9月登录）

Whats

楼主辛苦了！

阿旺

学习学习了，谢谢

Whats

{:soso_e113:}

石火刀刀

谢谢楼主的分享。

ivywen920

谢谢楼主，楼主可否整个可下载学习的，这样有点长奥

syhorchid

谢谢分享

咕咕

巴主英文突飞猛进啊

清风化雨

谢谢分享....

冰城

打个包好了，内容好多哦

龙之塬

谢谢楼主分享！

小小

学习了

waynes

楼主辛苦了！

cgc717

其中有几点值得商榷：
1、关于B类“Group B includes standard equipment and instruments providing measured values as well as equipment controlling physical parameters (such as temperature, pressure, or flow) that need calibration, where the user requirements are typically the same as the manufacturer’s specification of functionality and operational limits. ”B类包括提供测量所得数值的标准设备和仪器，以及控制需要校准的物理参数（例如温度、压力、或流动）的设备，其中用户需求通常与制造商的功能标准和操作限度相同。
是指物理参数要校准，还是指仪器要校准？
2、C类中的一段话“Installing these instruments can be a complicated undertaking and may require the assistance of specialists”安装这些仪器可以是一项负责的任务，并可能要求专家的协助。
是不是应该译成“安装这些仪器可认为是一项复杂的任务，可能需要专家的协助”

snow200289

学习了，谢谢

wmxwh

谢谢楼主的分享。

执行者

法规整理的不错。

华南疫苗李

感谢分享，楼主辛苦了！

huyun_520_88

谢谢啦法规整理的不错