Measurement Uncertainty and Conformity Assessment Applied to Drug and Medicine Analyses - A Review.

Analytical results are often used in scientific research, industrial and clinical applications to support decision making. Despite all efforts to ensure the reliability of analytical results (including method validation, internal quality control, use of certified reference materials, proficiency tests, and ISO 17025 accreditation), there will always be an uncertainty associated with the measured value. The measurement uncertainty expresses the quality of the analytical result and allows the comparability between analytical results or between the measured value and the specification limit(s). This work discusses the importance of measurement uncertainty, including the steps involved in the measurement uncertainty evaluation, the bottom-up and top-down approaches used in measurement uncertainty calculation, the measurement uncertainty evaluation in drug and medicine analyses, and the application of measurement uncertainty in conformity assessment for quality control, stability studies, and pharmaceutical equivalence.

Application of Measurement Uncertainty on Conformity Assessment in Pharmaceutical Drug Products.

BACKGROUND: Conformity assessment in pharmaceutical drug products usually are based on analytical results. An analytical result always is associated with an uncertainty which must be considered in a compliance assessment. OBJECTIVE: The objective of the present project aims to estimate the measurement uncertainty associated with the results of average weight, assay, uniformity of content, and dissolution testing in ranitidine tablets manufactured by two different companies (X and Y). METHODS: The uncertainty was evaluated using the Monte Carlo method. The particular and total risks of false acceptance decisions (consumers' risks) were also estimated by the Monte Carlo method. RESULTS: The results for ranitidine tablets manufactured by company X were (359.2 ± 2.7) mg of average weight, (108.6 ± 1.6)% of assay, (11.4 ± 2.8) of acceptance value for uniformity of content, and (89.4 ± 1.3)% for dissolution testing. The results for company Y were (312.5 ± 0.9) mg, (107.0 ± 1.4)%, (7.2 ± 1.7), and (93.6 ± 1.3)%, respectively. A 95% confidence level was adopted. According to results obtained from the Monte Carlo simulations, the results of average weight, assay of ranitidine, and uniformity of content are significantly correlated due to shared analytical steps. The correlation between values significantly affected the risk of false decisions. CONCLUSIONS: Consumers' risks were estimated for both ranitidine tablets and their results ensure compliance for ranitidine tablets manufactured by companies X and Y. HIGHLIGHTS: The use of measurement uncertainty is an important issue regarding the conformity/non-conformity assessment of pharmaceutical products.