<1058> ANALYTICAL INSTRUMENT QUALIFICATION

1 594 1057 Biotechnology-Derived Articles / General InformationUSP 35fluorescence of an individual specimen is read only onceincreasing sophistication and automation of ANALYTICAL instru-because irradiation decreases the fluorescent intensity.]ments, an increasing demand has been placed on users toqualify their The relationship of fluorescence to proteinUnlike method validation and system suitability activities,concentration is linear. Using the linear regression method, ANALYTICAL INSTRUMENT QUALIFICATION (AIQ) currently has noplot the fluorescent intensities of the solutions from thespecific guidance or procedures. Competing opinions existStandard Solutions versus the protein concentrations, andregarding INSTRUMENT QUALIFICATION and validation proceduresdetermine the standard curve best fitting the plotted the roles and responsibilities of those who performFrom the standard curve so obtained and the fluorescentthem.

2 Consequently, various approaches have been used forintensity of the Test Solution, determine the concentration ofinstrument QUALIFICATION , approaches that require varyingprotein in the test of resources and generate widely differing amountsof documentation. This chapter provides a scientific ap-Method 7proach to AIQ and considers AIQ as one of the major com-ponents required for generating reliable and consistent method is based on nitrogen analysis as a means ofNote that the amount of rigor applied to the qualificationprotein determination. Interference caused by the presenceprocess will depend on the complexity and intended use ofof other nitrogen-containing substances in the test specimenthe instrumentation. This approach emphasizes AIQ s placecan affect the determination of protein by this method. Ni-in the overall process of obtaining reliable data from analyti-trogen analysis techniques destroy the protein under testcal are not limited to protein presentation in an versus QualificationProcedure 1 Determine the nitrogen content of theprotein under test as directed under Nitrogen DeterminationIn this chapter, the term validation is used for manufac- 461.

3 Commercial instrumentation is available for theturing processes, ANALYTICAL procedures, and software proce-Kjeldahl nitrogen and the term QUALIFICATION is used for 2 Commercial instrumentation is availableThus, the phrase ANALYTICAL INSTRUMENT QUALIFICATION (AIQ)for nitrogen analysis. Most nitrogen analysis instruments useis used for the process of ensuring that an INSTRUMENT ispyrolysis ( , combustion of the sample in oxygen at tem-suitable for its intended approaching 1000 ), which produces nitric oxide(NO) and similar oxides of nitrogen (NOx) from the nitrogenpresent in the test protein. Some instruments convert theCOMPONENTS OF DATA QUALITY nitric oxides to nitrogen gas, which is quantified with athermal conductivity detector. Other instruments mix nitricThere are four critical components involved in the genera-oxide (NO) with ozone (O3) to produce excited nitrogention of reliable and consistent data (quality data).

4 Figure 1dioxide (NO2), which emits light when it decays and can beshows these components as layered activities within a qual-quantified with a chemiluminescence detector. A protein ref-ity triangle. Each layer adds to the overall quality. Analyticalerence material or reference standard that is relatively pureinstrument QUALIFICATION forms the base for generating qual-and is similar in composition to the test proteins is used toity data. The other components essential for generatingoptimize the injection and pyrolysis parameters and to eval-quality data are ANALYTICAL method validation, system suita-uate consistency in the tests, and quality control check samples. These qualitycomponents are described The protein concentration is calculated bydividing the nitrogen content of the sample by the knownnitrogen content of the protein.

5 The known nitrogen con-tent of the protein can be determined from the chemicalcomposition of the protein or by comparison with the nitro-gen content of the USP Reference Standard or referencematerial. 1058 ANALYTICAL INSTRUMENTQUALIFICATIONINTRODUCTIONA large variety of laboratory equipment, instruments, andFigure 1. Components of data ANALYTICAL systems, ranging from simple nitro-gen evaporators to complex multiple-function technologies(see INSTRUMENT Categories), are used in the pharmaceuticalindustry to acquire data to help ensure that products areAnalytical INSTRUMENT Qualificationsuitable for their intended use. An analyst s objective is toconsistently obtain reliable and valid data suitable for theAIQ is the collection of documented evidence that an in-intended purpose. Depending on the applications, users val-strument performs suitably for its intended purpose.

6 Use ofidate their procedures, calibrate their instruments, and per-a qualified INSTRUMENT in analyses contributes to confidenceform additional INSTRUMENT checks, such as system suitabilityin the validity of generated and analysis of in-process quality control check samplesto help ensure that the acquired data are reliable. With theOfficial from May 1, 2012 Copyright (c) 2011 The United States Pharmacopeial Convention. All rights from by nEwp0rt1 on Fri Dec 02 23:41:47 EST 2011 USP 35 General Information / 1058 ANALYTICAL INSTRUMENT Qualification595 Table 1. Timing, Applicability, and Activities for Each Phase of ANALYTICAL INSTRUMENT QUALIFICATION *OperationalPerformanceDesi gn QualificationInstallation QualificationQualificationQualificationT iming and ApplicabilityPrior to purchase of a newAt installation of each instrumentAfter installation orPeriodically at specified intervalsmodel of INSTRUMENT (new, old, or existingmajor repair offor each instrumentunqualified)

7 Each instrumentActivitiesAssurance of manufacturer sDescriptionFixed parametersPreventive maintenance andDQrepairsAssurance of adequate supportInstrument deliveryEstablish practices to addressavailability from manufactureroperation, calibration,maintenance, and change controlUtilities/facilityEnvironmentInst rument s fitness for use inlaboratoryAssembly and installationNetwork and data storageSecure datastorage, backup,and archiveInstallation verificationInstrument functionPerformance checkstests* Activities under each phase are usually performed as given in the table. However, in some cases, it may be more appropriate to perform orcombine a given activity with another phase. Such activities spanning more than one QUALIFICATION phase are shown as connected by doublearrows. If an activity listed under a given phase is performed under another phase, it is not necessary to repeat the activity under the phase wherethe activity is listed.

8 Performing the activity is far more important than the phase under which the activity is Method ValidationQualification PhasesAnalytical method validation is the collection of docu- INSTRUMENT QUALIFICATION is not a single continuous pro-mented evidence that an ANALYTICAL procedure is suitable forcess, but instead results from several discrete activities. Forits intended use. Use of a validated procedure with qualifiedconvenience, these activities can be grouped into fouranalytical instruments provides confidence that the proce-phases: design QUALIFICATION (DQ), installation qualificationdure will generate test data of acceptable quality. Additional(IQ), operational QUALIFICATION (OQ), and performance quali-guidance on validation of compendial procedures may befication (PQ).found in the general information chapter Validation of Com-Some AIQ activities cover more than one qualificationpendial Procedures 1225.

9 Phase, and analysts potentially could perform them duringmore than one of the phases (see Table 1). However, inmany instances there is need for specific order to the AIQS ystem Suitability Testsactivities; for example, installation QUALIFICATION must occurfirst in order to initiate other QUALIFICATION activities. The AIQS ystem suitability tests verify that the system will performactivities will be defined and documented. in accordance with the criteria set forth in the tests are performed along with the sample analyses toensure that the system s performance is acceptable at theDESIGN QUALIFICATION time of the test. USP general chapter Chromatography 621 presents a more detailed discussion of system suitability testsDesign QUALIFICATION (DQ) is the documented collection ofas related to chromatographic that define the functional and operational specifica-tions of the INSTRUMENT and criteria for selection of the ven-dor, based on the intended purpose of the INSTRUMENT .

10 De-Quality Control Check Samplessign QUALIFICATION (DQ) may be performed not only by theinstrument developer or manufacturer but also may be per-Many analysts carry out their tests on instruments stan-formed by the user. The manufacturer is generally responsi-dardized using reference materials and/or calibration stan-ble for robust design and maintaining information describ-dards. Some analyses also require the inclusion of qualitying how the ANALYTICAL INSTRUMENT is manufactured (designcontrol check samples to provide an in-process or ongoingspecifications, functional requirements, etc.) and testedassurance of the test s suitable performance. In this manner,before shipment to users. Nonetheless, the user should en-AIQ and ANALYTICAL method validation contribute to the qual-sure that commercial off-the-shelf (COTS) instruments areity of analysis before analysts conduct the tests.