Comparison of pharmacopeial statistical methods applied in microbiological assay for antibiotics potency determination using parallel lines and three-dose level

Abstract

Pharmaceutical equivalence studies, useful for checking the interchangeability of generic medicines and their respective innovator medicines, have been carried out in Brazil since 1999, as a consequence of the establishment of the generic medicine policy. For medicines containing antibiotics, microbiological assays are often the most appropriate method. However, the statistical methods applied in these assays are not widely known due to the difficult access to official codes and/or little knowledge of the statistical tools of analysis. Thus, the aim of this work was to compare the statistical methods for determining the potency of antibiotics through the cylinder-plate method using parallel lines and a three-dose level model, as described in the Brazilian Pharmacopeia (4th edition, 1988), British Pharmacopoeia 2011, European Pharmacopoeia (7th edition), The International Pharmacopoeia (4th edition), and United States Pharmacopeia (34th edition). The assay is illustrated with the antibiotic ofloxacin, and details on orthogonal coefficients, normality test, homogeneity of variance test, and detection of outliers are discussed. The calculations obtained by statistical analyses from different pharmacopeias lead to the same final interpretation. In practice, with the availability of alternative pharmacopeial methods, the analyst can choose the most appropriate statistical calculation to be used.