Analytical methods system suitability test

Validation of a chromatographic system is required by numerous quality assurance systems. For this purpose hardware, firmware, software and the analytical method used for analysis should be validated. Moreover, the chromatographic system needs to be tested against documented performance specifications for a given analytical method (system suitability test). Besides the prerequisites of a chromatographic separation, such as tailing factor, column... 

The procedure known as system suitability test consists in testing an instrumental analytical system against documented performance specifications for a given analytical method. System suitability tests are based on the concept that the equipment, electronics, analytical operations and samples constitute an integral system that can be evaluated as a whole. These tests are used to make sure that the resolution and reproducibility of the system are adequate for... 

System suitability allows the determination of system performance by analysis of a defined solution prior to running the analytical batch. System suitability should test the entire analytical system, chromatographic performance as well as the sensitivity of the mass spectrometer for the compounds of interest. Some LC-MS SOPs reference analytical methods as the source of operating details for a given analysis. This works particularly well for quantitative analysis, where analytical methods include critical details on instrument parameters and special calibrations that might be required for a particular analyte. Thus, system suitability testing provides the daily [3] checking of the system. 

In Phase III, the final dosage formulation has been established and the pivotal clinical trials are being conducted. Degradation products have been identified, so the method selectivity should be reevaluated to ensure that all degradants can be detected and quantitated. The analytical methods are completely validated, and appropriate for routine quality assurance and control purposes. The type and frequency of system suitable testing (SST) should be determined, and an excellent publication on SST for chromatography systems is available [47],... 

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. 

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). 

System suitability test characteristics and limits are recommended as a component of any analytical method. This ensures that both methodology and instrumentation are performing within expectations prior to the analysis of test samples. The test characteristics are inferred from robustness studies and evaluated during the validation experiments. 

System suitability tests are an integral part of analytical methods. They determine the suitability and effectiveness of the operating system. Analytical confidence in the obtained... 

The system suitability tests are performed to verify that the analytical system meets predefined acceptance criteria at the time of performance. System suitability parameters should be established based on the type of method being considered and before the validation of the method actually starts. A common method of system suitability will request bracketing reference injections, with measurable quantitative acceptance criteria, such a migration time and/or a range on the main peak area. The peak of interest can be the major peak but it can also be a secondary peak, which may give more control over the sample preparation (e.g., the HMW peaks in non-reduced CE-SDS or incomplete reduced in the case of reduced CE-SDS LIE). 

Fit the purpose calibration. It is common sense to check instrument performance each day, and GLP requirements simply formalize the performance and documentation of these checks. On the other hand, it is also important to use the right test (full calibration, verification, system suitability test, or instrument and method validation) to verify the performance and to avoid needlessly lengthy procedures. As already discussed (see Sections 13.2.3 and 13.3.1), it is not always necessary to perform a MS full calibration every day. For example, if a particular MS is used only to record complete full-scan mass spectra, a daily calibration or verification of the calibration of the m/z ratio scale is required. However, in the case where a MS is coupled with an LC and utilized primarily for the analysis of one or more analytes in the selected ion monitoring (SIM) mode, it does not always require a daily verification of the calibration. In this specific case it is quite common in LC-MS and LC-MS/MS applications to test only the following performance parameters (a) sensitivity, (b) system precision,... 

During method validation the parameters, acceptance limits, and frequency of ongoing system suitability tests or quality control checks should be defined. Criteria should be defined to indicate when the method and system are out of statistical control. The goal is to optimize these experiments in such a way that with a minimum number of control analyses the method and the complete analytical system will provide long-term results that will meet the objectives defined in the scope of the method. 

Suggested Analytical Method Use this section to present a complete description of the analytical method sufficiently detailed to enable persons skilled in the art to replicate it. Include all important operational parameters and specific instructions such as reagent preparation, systems suitability tests performance, description of blanks used, precautions, and explicit formulas for calculating test results. 

Therefore, a system suitability test with a known set of probes such as MIX 1 could be used as an internal test to provide further conhdence in regard to the batch-to-batch reproducibility of the packing material and/or to observe if the bonded phase has been compromised. This could also be used to probe the lot-to-lot reproducibility of new types of stationary phases that are available on the market. Once this simple and fast system suitability test is performed with MIX 1 and acceptable results are obtained using a set of defined acceptance criteria, the analysts may commence with his/her analytical method and run the specihc system suitability test stated in the method for their particular target pharmaceutical analyte. 

Phase 3. Analytical system suitability testing, which combines instmment, computer, and method. When the equipment and a particular method have been selected and validated, the equipment for that method goes through an SST prior to, and within, sample analyses, or practically on a day-to-day basis. 

Method validation should not be confused with system suitability tests. System suitability testing verified the suitability if an analytical system at the time the test is performed. 

Validation requires analytical method instructions comprising a system suitability test in order to verify identical starting conditions. Part or full revalidation may be considered if system suitability tests, or the results of quality control sample analysis, are out of pre-set acceptance criteria and the source of the error cannot be tracked back to instrumental factors or anything else. 

Careful consideration should be given in determining the necessity to include, and subsequently select criteria, for any required system suitability test which demonstrates the analytical technology will operate within the bovmdaries to provide valid analytical results. This may either include the use of reference materials or standards, as described above, which evaluate performance at the time of analysis. For nonchromatographic methods, this might include determining the accuracy of a wavelength determination, or an assessment of the reproducibility of the response to a test material. 

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