On-line TOC analysis
Jonathan Yourkin, global pharmaceutical product manager GE Analytical Instruments (Boulder, CO)
When comparing TOC data from similar samples analyzed by on-line and laboratory TOC instruments, observed variation can be attributed to two major sources: the sampling process used to introduce the sample to the measuring device and the inherent analytical capabilities of the analytical method. Given the ubiquitous presence of organics in the environment, grab-sample collection of TOC samples is subject to numerous error sources. With the on-line method, sampling-process variability is minimized or eliminated because the analyzer is physically integrated within the process-water stream for continuous quality-assurance monitoring. In addition, this evaluation quantifies sampling-process variation at TOC concentrations produced by the pharmaceutical water system, which are typically an order of magnitude lower than the TOC standard concentrations used to validate the analytical method. Sampling process variation is generally much more pronounced at these lower TOC concentrations.
Equivalency testing. Equivalency testing demonstrates the sameness of two measurement systems based upon the analytical results the methods produce. This type of testing differs from instrument-validation testing, which typically assesses various attributes using standards of known concentration. Validation protocols are not designed to identify differences in the test-sample data quality. Therefore, it is possible to validate two methods with the same protocols using the same criteria, yet have the methods yield nonequivalent analytical results under actual conditions of use. It is particularly important in on-line TOC implementations to augment validation protocols with equivalency testing. The fundamental hypothesis supporting the justification for measurment-system equivalency testing is that, given the sameness of on-line and laboratory analytical methods, any lack of equivalency observed between the two data sets can be attributed to aspects of the measurement system rather than the core analytical method.
This type of analysis is typically performed using a Gage Repeatability and Reproducibility (Gage R&R) study to quantify measurement-system variation relative to variation of the process as a whole. The Gage R&R addresses several components affecting variability, including the gauge (the instrument), the operator, and the sample itself. Ordinarily, a full-scale Gage R&R would be used to assess variability contributed by all components. This example uses a simplified Gage R&R approach based on the degree of sameness of the analytical methods and the unique differences in the operational or environmental conditions associated with laboratory and on-line measurements. By pairing the on-line and laboratory data collection, process water variability remains common between the two systems. In addition, the inherent accuracy of the instruments remains common, based on like-for-like methods that have been validated appropriately.