Evaluating Two PTI Test Procedures for Control of Delivered Dose Uniformity for Aerosol Products

Abstract

IPAC-RS developed a two-sided PTI test procedure in 2001 in response to the FDA draft guidance tests (FDA/CDER 1998; FDA/CDER 1999) for delivered dose uniformity for aerosol products. Subsequently, FDA proposed a two one-sided PTI test procedure (2005) to replace the original guidance test. The latter procedure was recently characterized and evaluated by Novick et al. (2009). The two procedures control product quality using different algorithms. In this article we evaluate the performance of these two procedures by simulations for different scenarios of parameter settings (mean, standard deviation, and sample size). Operating characteristic curves and contour plots for acceptance (or rejection) regions are generated to describe the consumer risk and the producer risk under each scenario. We apply the two procedures to batches produced under realistic simulated production situations and to mixtures of normally distributed DDU (delivered dose uniformity) data from simulated multidose products to illustrate the utility of these methods and assess their performance for control of delivered dose uniformity. Under the same parameter setting, the FDA two one-sided PTI procedure is consistently more conservative than the IPAC-RS two-sided PTI procedure. However, when dealing with products with low quality or products with contamination, the FDA PTI test exhibits a more desirable performance characteristic than the IPAC-RS PTI test. We found that the performance of the FDA two one-sided PTI test can be markedly improved by using the exact K value of the tolerance factor used in the construction of its PTI test.

Keywords:

• Consumer risk
• Contour plot
• Operating characteristic curve
• Parametric tolerance interval
• Producer risk

Acknowledgments

The authors thank Dr. Jayne Zimmerman for valuable discussions regarding industry perspectives on many issues discussed in this article. They also thank the Editor, the Associate Editor, and two anonymous referees for their critical comments and constructive suggestions that improved the earlier version.