Pure and Applied Chemistry

Abstract: A metrological background for investigating out-of-specification (OOS) test results of chemical composition is discussed. When an OOS test result is identified, it is important to determine its root causes and to avoid reoccurrence of such results. An investigation of the causes based on metrological concepts is proposed. It includes assessment of validation data of the measurement process and its metrological traceability chains, evaluation of measurement uncertainty, and related producer’s and consumer’s risks. This approach allows distinguishing between OOS test results that indicate an actual change in chemical composition of an analyzed object, and OOS test results that are metrologically related with a certain confidence probability, i.e., caused by measurement problems, while the analyzed object still meets the specification requirements at the time of testing. Practical examples illustrating applications of the described approach in environ-mental and food analysis, as well in drug analysis and stability study of drug products, are described. Acceptance limits, warning and action lines for the test results, and corresponding producer’s and consumer’s risks are discussed.