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Assurance of manufacturers DQ Assurance of adequate support availability from manufacturer Instruments fitness for use in laboratory
Preventive maintenance and repairs Establish practices to address operation, calibration, maintenance, and change control
Secure data storage, backup, and archive Installation verification Instrument function Performance checks tests * 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.
Environment
tests, and quality control check samplesare not within the scope of this chapter.
Qualification Phases
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). 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.
DESIGN QUALIFICATION
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.
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. DescriptionProvide 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. Instrument DeliveryEnsure 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. Utilities/Facility/EnvironmentVerify that the installation site satisfactorily meets manufacturer-specified environmental requirements. Assembly and InstallationAssemble 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 userspecific criteria. Network and Data StorageSome 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. Installation VerificationPerform the initial diagnostics and testing of the instrument after installation.
INSTALLATION QUALIFICATION
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
OPERATIONAL QUALIFICATION
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
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in the selected environment. Testing activities in the OQ phase may consist of these test parameters. Fixed ParametersThese 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. [NOTEThese 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.] Secure Data Storage, Backup, and ArchivingWhen applicable, test secure data handling such as storage, backup, audit trails, and archiving at the users site according to written procedures. Instrument Function TestsInstrument 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. 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. 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. 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.
PERFORMANCE QUALIFICATION
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. Performance ChecksSet 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. Testing frequency depends on the ruggedness of the instrument and the criticality of the tests performed. Testing may be unscheduledfor example, each time the instru-
Quality Unit
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.
Manufacturers
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. Finally, it is desirable that manufacturers and vendors should notify all known users about hardware defects discovered after a products release; offer user training, service, repair, and installation support; and invite user audits as necessary.
SOFTWARE VALIDATION
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
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Firmware
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 users 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).
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. Operational QualificationRevise OQ tests as necessitated by the change. Perform the relevant tests affected by the change. This ensures the instruments effective operation after the change is installed. Performance QualificationRevise 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. 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 changed functionality.
AIQ DOCUMENTATION
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.
INSTRUMENT CATEGORIES
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. 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.
Stand-Alone Software
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.
CHANGE CONTROL
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. 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
General Principles 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.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085281. htm (accessed December 2012.
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Group A
Group A includes standard equipment with no measurement capability or usual requirement for calibration, where the manufacturers 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.
Group B
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 manufacturers specification of functionality and operational limits. Conformance of Group B instruments or equipment to user requirements is deter-
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mined 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 viscometers. Examples of equipment in this group are muffle furnaces, ovens, refrigerator-freezers, water baths, pumps, and dilutors.
Group C
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: