IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report)

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.

Validation of a chromatographic method to routine analysis of trans-resveratrol and quercetin in red wines

“…In this way, it is possible to identify possible laboratory errors related to the standard curve. The control chart data can be used as research aid, in case of results from areas outside the specification, as indicated by the FDA (2006) and Kuselman et al (2012).…”

IUPAC/CITAC Guide: Classification, modeling and quantification of human errors in a chemical analytical laboratory (IUPAC Technical Report)

“…When f HE exceeds 68 %, u HE increases with f HE dramatically. In the theoretical case of f HE = 100 %, formulas (12) and (14) tend to infinity. However, such a contribution of human error to uncertainty is not realistic, inasmuch as the error becomes apparent: it will be identified and treated.…”

“…An important group of atypical results is out-of-specification test results that fall outside the established specifications in the pharmaceutical industry, or do not comply with regulatory, legislative, or specification limits in other industries and fields, e.g. environmental and food analysis [11,12]. Such results may also not meet the established/agreed requirements for a non-regulated product under chemical analysis.…”

Human Errors and Out-of- Specification Test Results

“…An investigation of the causes based on metrological concepts is proposed in the corresponding IUPAC/CITAC (Cooperation on International Traceability in Analytical Chemistry) Guide 2012. 2 This approach allows distinguishing between OOS test results, which indicate an actual change in chemical composition of an analyzed object, and OOS test results, which are metrologically related with a certain confidence probability (i.e., caused by measurement uncertainty and other metrological problems). However, it is known that human activity is never free from errors: about 70 percent of incidents and accidents are caused by human errors.…”