System suitability laboratory instrument

Imagine that you are working with one of the forensic science analytical testing companies and have just undertaken a piece of work at the request of the crown prosecution service. You have analysed a brown powder and found it to contain 70% of the controlled drug diamorphine (heroin). The counsel for the defence has requested that the sample be analysed by an independent laboratory of its choosing. The sample is reanalysed and there is a dispute in relation to the result because the defence analyst finds only 10% of the controlled drug diamorphine. You attend court and are asked to justify your results. Your lab has a rigorous quality assurance system that includes method validation, system suitability, and instrument qualification the defence lab does not. Your result is accepted as the correct value. 

In the first phase, the performance of the instrumentation used for the method is demonstrated. Based on the analysis of standards, results from the participating laboratory should meet the system suitability requirements of the method. Successful completion of this phase will qualify the analyst, his or her equipment, and the laboratory for the trial. Failure in the first phase does not usually cause a method to fail the trial. However, it can slow the process. When a procedure fails during the first phase of a trial, the sponsor may need to write a cautionary note in the SOP discussing recommended or inadequate types of instruments. To correct the problem, the participating laboratory analyst can substitute equipment that gives adequate performance alternatively, the sponsor must find a different laboratory to participate in the trial. 

It is being recognized increasingly that regulation can have a positive impact on laboratory productivity.36 System suitability testing has been proposed as superior to and supplemental to calibration in the UV-VIS detector.37 Large variations in both response factor and in relative response factors were observed on different instruments. Even on the same instrument, UV-VIS spectra can be extremely dependent on solution conditions, as was observed in a separation of hypericin, the antidepressant extract of St. John s wort.38... 

Good Laboratory Practice (GLP) The system provides a comprehensive feature set to aid customers in meeting GLP requirements. This includes features such as certificate-of-software validation, user-access levels, instrument and sequence logbooks, system-suitability software for aU supported HP instruments, standard GLP reports, and a GLP save option that encrypts and saves data and methods together. 

There is usually no problem of access to basic laboratory instruments and associated glassware, however, the only means of handling large numbers of tests is to apply some form of automation. An added advantage is that it improves the analytical precision and reproducibility. The most suitable technique has been based on the segmented continuous-flow principle invented by Skeggs (1957), and which was first marketed as the Technicon AutoAnalyzer. The system consists of a number of modules powered from a stabilized 110 V supply, and a typical layout is shown in Fig. 1.1. 

The fundamental purpose of laboratory instrument validation is to provide assurances that the instrument is suitable for its intended use. The assurance is supported by documented evidence that the system consistently performs according to predetermined specifications for its intended applications. 

The validation of an analytical procedure produces performance parameters of a well-behaved and well-conditioned system/instrument (including defined variations) which are more or less snapshots of the combination procedure/system. In order to routinely confirm the suitability of the integrated measurement instrumentation used with a given procedure, system suitability test parameters should be defined on the basis of the validation results and robustness studies. Larger variations under routine conditions or multiple laboratories should also be taken into consideration. 

The final step in the development of a method is to establish the requirements for speed versus the necessary specificity. In short, a method may perform better in terms of specificity if a broad spectral region is used in a comprehensive che-mometric model, but the duration of data acquisition may not be suitable for the application. The opposite is also true, where a single- or dual-wavelength measurement may meet the ideal speed target, but fail in terms of specificity. Various instrumental platforms are available on the market, and it is imperative that a balance between these parameters be achieved for a method to ever reach deployment. For laboratory-based methods, specificity is often much more important than speed, reinforcing the need for a hyperspectral imaging system, if the instrument is to be used for quality control, then speed should be considered in the development of the method. It is important to bear in mind that speed and specificity are not mutually exclusive indeed, they can often both be achieved if the method is properly targeted to the question at hand. 

The USP definition of robustness equals that of the ICH (3) The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. A robustness test is the experimental setup used to evaluate method robustness. It quantifies the insensitivity of the results for a method transfer to another laboratory or instrument. The ICH guidelines also state that One consequence of the evaluation of robustness should be that a series of system suitability parameters (eg., resolution tests) is established to ensure that the validity of the analytical procedure is maintained whenever used (3). 

Method transfer between instruments and laboratories may require some revalidation in CE due to differences in the construction of the instruments, especially the detector and injection systems. Therefore, it is preferable to specify an injection volume that is independent of a specific instrument. To assess the performance of a method in routine analysis system suitability tests comparable to HPLC such as selectivity, resolution, or system precision are recommended. Peak symmetry is not considered as the injection of high concentration often leads to peak distortion in CE. 

Each laboratory should have a quality assurance program which should be well understood and used by individuals as well as by laboratory organizations to prevent, detect, and correct problems. The purpose is to ensure that the results have a high probability of being of acceptable quality. Ongoing activities may include preventative instrument maintenance, performance verification and calibration, system suitability testing, analysis of blanks and quality control samples, and ensuring system security. A plan should be set up to... 

The fluids which are used in the hydraulic fracturing process can be quite complex. Laboratory research and development on these fluids require many hours of rheology testing to discover suitable compositions and systems. To speed this process, an automated stimulation fluid rheology laboratory was constructed. In this paper, we describe the types of instruments which are used in this laboratory, the computer system, and how t.vr cal experiments are set up, run, and results stored and analyzed. In the accompanying paper (Part II), the focus is on the automation of one of the more complex Instruments in this laboratory. 

In addition, a system for making sure staff are appropriately qualified and trained for the work that they are doing must be in place. This will enable an auditor to see clearly the demonstrated competence of the staff and how this has been checked. The requirements for all major items of equipment must be listed, to ensure that the equipment in use is suitable for the task, is in working condition and, where necessary, is calibrated. For all of the instrumentation there needs to be a documented schedule for maintenance. Measurements must be traceable, that is, the laboratory must be able to show how the calibration of measurement instruments is traceable to National or International Standards. Where this presents practical problems, as in some chemical measurements for example, interlaboratory comparison and the use of reference materials (and preferably Certified Reference Materials) will be required. 

Automation has been applied for a number of years in process control instrumentation, but the major impetus to introduce automatic devices into laboratories stems from three sources (1) the introduction of the continuous-flow principles as outlined by Skeggs [1] (2) the general demand for clinical chemical measurements, which represents a ready and sizeable market for instrument companies, and, more importantly, (3) the abihty to handle large volumes of data and package them in a form suitable for presentation to analysts and customers, through the use of mini- and micro computer systems hnked to a control computer. 

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. 

Different capillary columns are available for organic acid separation and analysis. In our laboratory, the gas chromatography column in all GC-MS applications is crosslinked 5% phenyl (poly)methyl silicone, 25 m internal diameter 0.20 mm stationary phase film thickness 0.33 pm (Agilent HP-5, DB-5, or equivalent). Several instrument configurations are commercially available, which allow for positive identification of compounds by their mass spectra obtained in the electron impact ionization mode. A commercially available bench-top GC-MS system with autosampler (Agilent 6890/5973, or equivalent) is suitable. Software for data analysis is available and recommended. The use of a computer library of mass spectra for comparison and visualization of the printed spectra is required for definitive identification and interpretation of each patient specimen. 

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