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Much improvement has taken place in evaluating sources of variability in the measures of delivered dose uniformity (DDU) and aerodynamic particle size distribution (APSD). Methods described in the United States Pharmacopeia (USP) and European Pharmacopoeia (Pharm. Eur.) now include dimensions and diagrams for all components critical to their robustness. However, we show that there are sources of bias in the standard methods for DDU. A future article will address APSD. Inhalation April 2023 21 Exploring the robustness of the pharmacopeial methods for testing dry powder inhalers (DPIs); Part 1: Delivered dose uniformity (DDU) Uncovering the potential for systematic bias in the pharmacopeial test protocol Daryl L. Roberts, PhD a and Jolyon P. Mitchell, PhD b a Applied Particle Principles, LLC b Jolyon Mitchell Inhaler Consulting Services Inc. Introduction Much improvement has taken place during the past 20 years on the subject of evaluating sources of vari- ability in the resulting measures of delivered dose uniformity (DDU) and aerodynamic particle size distribution (APSD). e methods described in the United States Pharmacopeia (USP) [1] and Euro- pean Pharmacopoeia (Pharm. Eur.) [2] now include dimensions and diagrams for all components that are critical to their robustness. e question of bias has not, however, been carefully addressed in the same way. Bias is, in its simplest form, a systematic error, conveying information about the accuracy of the measurement being made. Bias is demonstrated by a shift in the mean value from the true value of the sought metric if more than one replicate mea- surement is made. In contrast, variability is the ran- dom error that is always associated with replicate measurements made with real-world instruments that themselves have random uncertainty. Vari- ability is often expressed by the standard deviation about the mean measurement value from a series of replicate measurements. Control of the volumetric flow rate into sampling apparatuses for the performance testing of all types of passive dry powder inhalers (DPIs) is critical, as this measure influences the kinetics associated with mass transfer of the active pharmaceutical ingredi- ent(s) (API(s)) from the inhaler to the measurement apparatus [3]. For example, a lower actual flow rate than the expected value from the measurement will affect the imparted energy-time profile to the powder, thereby resulting in slower aerosol generation, pow- der dispersion and transfer [4]. However, and per- haps surprisingly, volumetric flow rate is a dependent variable in the standard pharmacopeial protocols. Given this situation, it is incumbent for stakehold- ers to be aware of sources of potential bias to have complete confidence in this important inhaler per- formance measure. In this article, we show that there are sources of bias in the standard methods for DDU, and in a future article in Inhalation, our aim will be to extend the analysis to the measurement of APSD. Defining the problem e test for delivered dose uniformity (DDU) of a passive DPI has three discrete stages: a. drawing air through the device at a rate sufficient to impart a pressure drop of nominally 4 kPa across the device, b. removing the device and measuring the flow rate to enable the calculation of the test run time required to draw two liters of air through the device, and c. reattaching the device and dispensing the dose by drawing air through the device for the specified run time.