Leontiev D. Development of a system of pharmaceutical reference standards in Ukraine

The dissertation is devoted to developing and implementing a system of reference standards (RS) into the Ukrainian pharmaceutical industry. To evaluate the total uncertainty (expanded), a linear model based on the summarizing of squares of confidence intervals of partial components of the uncertainty has been proposed. The principle of insignificance was formulated for reliability 95 %: a partial component of the uncertainty should not exceed 0,32 of the total uncertainty. Requirements for the maximum acceptable uncertainty of results of the analysis for major pharmaceuticals tests have been substantiated. It is proven that the maximum acceptable uncertainty of the RS certified value should not exceed 0,32 of the maximum acceptable uncertainty of results of the analysis. The requirement that partial uncertainty should not exceed 0,32 of the RS maximum acceptable uncertainty was suggested to an all partial uncertainty components for primary and secondary RS (the establishment of the certified value, homogeneity, stability). A system of working RS was developed and implemented at 14 laboratories of Ukrainian drug manufacturers. The proposed principles were applied to test samples for the proficiency testing program. The system of pharmacopoeial reference standards of the State Pharmacopoeia of Ukraine (PhRS SPhU) was established. The nomenclature of the PhRS SPhU exceeds 600 titles.