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.