Qualification instruments

Ensuring that the instrument to be used performs correctly is the first step in developing an instrumental methodology. The European Pharmacopoeia and the guidelines of the Pharmaceutical Analytical Sciences Group (PASG) recommend that NIR instruments be qualified as per the manufacturer s instructions, which should include at least the following  

Checking for wavelength repeatability by using one or more suitable standards (e.g. polystyrene or rare-earth oxides). The repeatability of measurements should be consistent with the spectrophotometer specification. 

Checking for photometric linearity by the use of a set of transmittance or reflectance standards (e.g. Spectralon, carbon black mixtures). 

Checking for the absence of photometric noise by using a suitable reflectance standard (e.g. white reflective ceramic tiles or reflective thermoplastic resins, such as Teflon). The reflectance standard should be scanned in accordance with the recommendations of the spectrophotometer s manufacturer and peak-to-peak photometric noise calculated over a specified wavelength region. The amount of photometric noise should be consistent with the spectrophotometer specification.  

The instrument qualification process tests the functioning of each component of the instrument individually, compares the results against preset manufacturer s specifica- 

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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. 

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... 

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). 

These components, rigorously interconnected, enable analytical chemists to produce accurate and reproducible data when unknown samples are analysed. Especially the two basal compartments are of crucial importance analytical methods validation and analytical instrument qualification. 

Calibration, in current Good Manufacturing Practices (GMP) terminology, refers to instrument qualification or performance verification... 

Calibration, in current Good Manufacturing Practices (cGMP) terminology, refers to instrument qualification or performance verification of the HPLC. Note that neither any internal instrumental adjustment nor detector response curve for quantitation is intended here as in the common usage of the terminology. In most pharmaceutical laboratories. 

As with any data generation or data-handling system, appropriate validation (instrument qualification (IQ)/operational qualification (OQ)/performance qualification (PQ)) is required to demonstrate that the system is accurately and reliably performing in accordance with the user-functional requirements. 

For the pharmaceutical scientist, understanding the theory and application of the equipment is usually not sufficient there is the matter of compliance. The qualification of CE is similar to that of other instruments. Installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) apply in much the same way as high-performance liquid chromatography (HPEC). This chapter details the different parts of the modern CE instrument, equipment-related issues and troubleshooting, instrument qualification, and the future of the CE instrument. 

Instrument qualification or validation refers to the process of demonstrating an instrument s suitability for its intended use. The first step is to write protocols to cover the four main qualification elements design qualification, installation qualification, operational qualification, and performance qualification. Another qualification element, re-qualification, can be written as a separate protocol or included as part of the PQ protocol. These protocols must be performed in sequence. If the protocol meets its acceptance criteria, then the next protocol in the sequence can be executed. 

The computer system attached to the instrument provides instrument control, data acquisition, data processing, and reporting. According to the draft Analytical Instrument Qualification chapter of the United States Pharmacopoeia (USP) <1058> The manufacturer should perform design qualification, validate the software and provide users with a summary of the validation. At the user site, holistic qualification that involves the entire instrument and software system is more efficient than modular validation of the software alone. Therefore the user qualifies the instrument control, data acquisition and processing software by qualifying the instrument. ... 

This statement suggests that provided the manufacturer has performed and adequately documented the functions mentioned in the Analytical Instrument Qualification chapter no further qualification activities that are specific to the software is required by the user of the instrument. 

Analytical Instrument Qualification, Pharmacopeial Forum 32(6), November 2006. 

This chapter deals with the validation of capillary electrophoresis (CE) methods. It describes the various validation characteristics, namely accuracy, precision, specificity, detection limit, quantitation limit, linearity, and range in accordance with the official guidelines. Practical aspects related to the calculation of these parameters and factors affecting them in CE analysis have also been described. Validation requirements have been described according to the goal of the method. The chapter contains numerous tables and diagrams to illustrate these ideas. It also covers other related aspects such as instrument qualification, revalidation, and method transfer. 

Similar to method validation, it is important to be able to demonstrate that analytical instrumentation is fit for its intended purpose and that it is calibrated and maintained in an appropriate state of readiness. The verification of instrument qualification (see Chapter 8)... 

TABLE 9 Important Aspects of Instrument Qualification/Validation and System Suitability (Cf. References I, 2, and 20)... 

The terms instrument qualification and instrument validation are sometimes used indiscriminately. In this chapter, the term qualification refers to the site preparation and the testing employed to demonstrate that the instrument is properly installed in a suitable environment and the performance meets the predetermined specifications for its intended use. Qualification is a part of the whole validation life cycle. Validation refers to the process to provide assurance that the instrument is suitable for the intended application throughout the lifetime of the instrument. Installation qualification (IQ), operation qualification (OQ), and performance qualification (PQ) are performed to provide evidence that the user requirement specifications (URSs), functional requirement specifications (FRSs), and design qualification (DQs) have been met. The sequence of requirements setting and qualification events as well as the relationships between IQ, OQ, PQ and URS, FRS, and DQ are generally illustrated by the V diagram shown in Figure 2. Installation qualification demonstrates the fulfillment of the DQ. Similarly, OQ demonstrates the fulfillment of the functional requirements and PQ demonstrates the fulfillment of the user requirements. 

U.S. Pharmacopoeia (USP) (2006), general chapter (1058), Analytical instrument qualification, USP, Rockville, MD. 

The information in this chapter applies specifically to the first element sample preparation. The sample preparation steps are usually the most tedious and labor-intensive part of an analysis. By automating the sample preparation, a significant improvement in efficiency can be achieved. It is important to make sure that (1) suitable instrument qualification has been concluded successfully before initiation of automated sample preparation validation [2], (2) the operational reliability of the automated workstation is acceptable, (3) the analyte measurement procedure has been optimized (e.g., LC run conditions), and (4) appropriate training in use of the instrument has been provided to the operator(s). The equipment used to perform automated sample preparation can be purchased as off-the-shelf units that are precustomized, or it can be built by the laboratory in conjunction with a vendor (custom-designed system). Off-the-shelf workstations for fully automated dissolution testing, automated assay, and content uniformity testing are available from a variety of suppliers, such as Zymark (www.zymark.com) and Sotax (www.sotax.com). These workstations are very well represented in the pharmaceutical industry and are all based on the same functional requirements and basic principles. 

The instrument qualification and calibration records are among the most frequently requested items in regulatory inspections. It is vital for the pharmaceutical, biotechnology, environmental, food, cosmetic, and chemical laboratories to maintain a rigorous instrument qualification and performance... 

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