A two one-sided parametric tolerance interval test for control of delivered dose uniformity--part 2--effect of changing parameters.

This article examines the effects of changing parameters in the test which was proposed by the FDA at the October 2005 Advisory Committee meeting for confirming delivered dose uniformity in orally inhaled and nasal drug products. This article is an extension of the characterization study presented in an accompanying article (Part 1). The goal of this study is to understand how parameters of the test affect the test performance.

A two one-sided parametric tolerance interval test for control of delivered dose uniformity. Part 1--characterization of FDA proposed test.

The FDA proposed a parametric tolerance interval (PTI) test at the October 2005 Advisory Committee meeting as a replacement of the attribute (counting) test for delivered dose uniformity (DDU), published in the 1998 draft guidance for metered dose inhalers (MDIs) and dry powder inhalers (DPIs) and the 2002 final guidance for inhalation sprays and intranasal products. This article (first in a series of three) focuses on the test named by the FDA "87.5% coverage.

A two one-sided parametric tolerance interval test for control of delivered dose uniformity--part 3--investigation of robustness to deviations from normality.

The robustness of the parametric tolerance interval test, which was proposed by the Food and Drug Administration for control of delivered dose uniformity in orally inhaled and nasal drug products, is investigated in this article using different scenarios for deviations from a univariate normal distribution. The studied scenarios span a wide range of conditions, the purpose of which is to provide an understanding of how the test performs depending on the nature and degree of the deviation from normality. Operating characteristic curves were generated to compare the performance of the test for different types of distributions (normal and non-normal) having the same proportion of doses in the tails (on one or both sides) outside the target interval.