Instrument Qualification Instrumentation

KSC increases the failure rates of components from causes such as earthquake, fiic. flooding, tornado, erroneous maintenance or inis-sp>ecifying the operating cnvironmcni. [ nvironmental qualification (EQ) of equipment, specified by Regulatory Guide 1.97, as.surcs ihc operation of instruments in an accident environment. Similar qualification is required for a tiesi uu-basis earthquake. 

Installation qualification involves performing checks to ensure that the correct equipment or system has been installed and/or connected, including all necessary controls, monitors, instrumentation, or ancillary services. These checks should include verification that relevant operator manuals or instructions have been received from the supplier and that any applicable calibration steps have been identified. 

In a GLP-compliant laboratory, a data system must meet explicit requirements guaranteeing the validity, quality, and security of the collected data. Operational qualification (OQ) must be performed after any new devices are installed in the laboratory system and whenever service or repair are performed. The role of OQ is to demonstrate that the instrument functions according to the operational specifications in its current laboratory environment. If environmental conditions are highly variable, OQ should be checked at the extremes in addition to normal ambient conditions. Performance qualification (PQ) must be performed following any new installation and whenever the configuration of the system has been changed. PQ demonstrates that the instrument performs according to the specifications appropriate for its routine use. 

Validations fall into two types prospective and retrospective. In prospective validation (see flow chart in Figure 2) the validation is done in a sequential manner, involving installation qualification and operational qualification (IQ/OQ) of equipment (e.g., chromatography instrumentation or column hardware). Appropriate calibrations accompany the IQ/OQ. Process qualification, or PQ, involves formal review and approval of a PQ protocol, execution of this protocol, and issuance of a formal PQ report which includes data analysis and recommendations (i.e., approval/certification of the process). If the process is not approved, the report may recommend a redesign or redoing of the validation protocol and, in some cases, a return of the process to process development for further optimization. 

The texts are for those interested in the basics of analytical chemistry and instrumental techniques who wish to study in a more flexible way than traditional institute attendance or to augment such attendance. A series of these units may be used by those undertaking courses leading to BTEC (levels IV and V), Royal Society of Chemistry (Certificates of Applied Chemistry) or other qualifications. The level is thus that of Senior Technician. 

It is important that any method chosen is scientifically sound under the conditions it will be applied. It is also necessary to demonstrate that the equipment, which will be used, is suitable and its use will not influence the results adversely. This includes all types of equipment, e.g. does the volumetric glassware have a suitable tolerance and do the instruments have sufficient sensitivity over the entire range of measurement The process for demonstrating equipment capability is called equipment qualification and is dealt with in Chapter 5. The staff carrying out validation need to be both qualified and competent in the tasks that they need to carry out. 

All equipment has limitations, for example, the amount of a substance it can detect or the accuracy with which it can make a measurement. If you attempt to make the equipment perform beyond its capabilities, it does not matter how carefully the equipment is operated, it will not be possible to get meaningful results. In terms of a particular instrument, fitness for purpose is interpreted as having appropriate performance capability to do the work required. This applies to all equipment, large or small. For example, a stirrer needs to perform the intended task satisfactorily while remaining essentially inert. There is a formal process for assessing the suitability of equipment to perform a given task - this is called Equipment Qualification or Equipment Validation. This is dealt with in Section 5.6.3. 

Installation qualification is aimed primarily at new instruments. This is the stage when the checks are carried out to confirm that the instrument received is as specified and correctly installed in the selected environment. This includes both hardware and software. It may be convenient to use a check-list approach to this phase as that ensures everything is checked. This stage covers the installation up to and including its initial response to power, if that is relevant. In addition it may be appropriate to repeat aspects of IQ following relocation or upgrades of instruments. 

Operational qualification establishes that an instrument will function according to its specification in the selected environment. The role of OQ can be considered as demonstrating that an instrument s key operating parameters are within specification and there are no unacceptable differences between the parameters... 

It is always recommended that OQ is carried out after a service visit. Evidence of continued satisfactory performance during use (PQ) should be obtained from everyday method-related checks (e.g. system suitability testing, calibration and analytical quality control). It is advisable to set up thresholds outside of which the performance of an instrument is no longer acceptable. Each stage of the equipment qualification needs to be fully documented so that the evidence of performance at any given time can be checked. 

The computerized systems, both hardware and software, that form part of the GLP study should comply with the requirements of the principles of GLP. This relates to the development, validation, operation and maintenance of the system. Validation means that tests have been carried out to demonstrate that the system is fit for its intended purpose. Like any other validation, this will be the use of objective evidence to confirm that the pre-set requirements for the system have been met. There will be a number of different types of computer system, ranging from personal computers and programmable analytical instruments to a laboratory information management system (LIMS). The extent of validation depends on the impact the system has on product quality, safety and record integrity. A risk-based approach can be used to assess the extent of validation required, focusing effort on critical areas. A computerized analytical system in a QC laboratory requires full validation (equipment qualification) with clear boundaries set on its range of operation because this has a high... 

As with any analytical instrumentation, processes that involve both operation qualification and performance qualification are implemented during manufacture of the instrumentation for /tPLC described in this chapter to ensure that the instrument will perform according to specifications. 

During operation qualification, all components of the instrument are tested individually along with integral parts of the overall instrumentation. In this section, results of some of the most common performance parameters are presented with a brief description of the methods used for evaluation. 

Thus, while a well-maintained instrument is important for any chemical/physical measurement, in NIR, without a concurrent standard for comparison, it is critical that the instrument be continuously calibrated and maintained. Since the major manufacturers of equipment have worked with the pharmaceutical industry, this has been formalized into what is called IQ/OQ/PQ, or Instrument Qualification, Operational Qualification, and Performance Qualification. The first is routinely performed (at first) by the manufacturer in the lab/process location, the second in situ by the user with help from the manufacturer, and the third is product/use dependent. These formal tests apply to all instruments in any industry. 

To ensure that equipment is fit for its intended purpose, there is a series of qualifying steps that the analyst or vendor should apply to analytical instrumentation (3,4). Equipment can be evaluated through a series of tests or procedures designed to determine if the system meets an established set of specifications governing the accepted operating parameters. The successful completion of such tests justifies that the system operates and performs as expected. There are four components of instrument qualification design, installation, operational, and performance. 

C. During operational qualification the analyst or vendor would assess if the equipment works as specified, generating appropriately documented data. The procedures will verify that the instrument s individual operational units are functioning within a given range or tolerance, reproducibly. For the dissolution apparatus, the water bath temperature and spindle assembly and shaft rpm speed would be obvious operational parameters. 

Burgess C, Jones DG, McDowall RD. Equipment qualification for demonstrating the fitness for purpose of analytical instrumentation. Analyst 1998 123 1879-1886. 

Instrument qualifications are the tests that are performed after the equipment is installed for use in a laboratory. Instrument qualifications include installation qualification, operational qualification, and performance qualification. These tests verify that the equipment is installed, operates, and performs according to the manufacturer s specifications. Each of these types of qualifications is defined in more detail in the following sections. 

For the purposes of instrument qualification, the PQ involves testing the equipment for overall system functionality. For dissolution equipment, these tests verify that the equipment can perform the entire dissolution process. A sample method should be observed to run properly. This can include running actual chemistry and analyzing the data results. 

When designing instrument qualifications for automated dissolution systems, some key considerations are determining the functions to validate, cost, testing using equipment... 

Equipment manufacturers are faced with the challenge of qualifying all the functionality of complex equipment at the customer s lab while keeping the costs at a reasonable level. There is an expectation that the cost to qualify laboratory instrumentation be only a small fraction of the cost of the equipment itself. However, there are costs associated with both developing the qualification protocols and executing the qualification protocols. 

It is often the case that laboratories combine the use of equipment from more than one manufacturer into systems that need to be qualified. Each individual device must be qualified for the functionality of that device. Sometimes one manufacturer will sell and qualify other manufacturers devices that connect to their equipment. In this case, one company is responsible for the instrument qualifications of the entire integrated system. It is usually required that each manufacturer qualify its own device, and that following the qualification of the individual devices, the manufacturer that supplies the interface must then qualify the interfaces between the devices. 

While there are many different formats that can be used for instrument qualifications, there is a minimum amount of information that needs to be provided as part of the testing. 

Instrument qualifications should be executed on a scheduled basis that can be determined with the help of manufacturer s recommendations. Automated dissolution systems that are used regularly are typically re-qualified every six months to one year. Re-qualification is also recommended for other reasons including moving equipment or replacing parts. Below is a typical system re-qualification policy. 

The manufacturer often creates an instrument qualification plan and provides installation, operational, and performance qualifications to be executed in the customer s laboratory. The company using the equipment must determine if the manufacturer supplied instrument qualifications is comprehensive enough to be sure that the equipment is installed, operating, and performing correctly. If they feel it is not, they may choose to perform more tests themselves. 

There are four general steps to ensure this control and consequently to guarantee the data quality [32] quality control checks (QC), system suitability tests (SSTs), analytical methods validation (AMV), and analytical instrument qualification (AIQ) (see Figure 5). 

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