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Scientific and Regulatory Considerations on Particle Characterization and Specification Setting for Dry Powder Inhalers

Sun Z.

RDD Europe 2017. Volume 1, 2017: 175-176.

Abstract:

Dry powder inhaler (DPI) technology is a leading approach in pulmonary drug delivery for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and respiratory infections. Inter-particle interactions and aerosol properties have a significant impact on DPI performance, so particle engineering provides an effective approach for development and optimization of particulate formulations to ensure efficient drug delivery, as well as optimal therapeutic outcomes. The control of “engineered” particles in DPIs has become one of the critical aspects in their development and quality control due to the large influence of particle characteristics (e.g., size, shape, density, surface roughness, surface area, etc.) on performance and/or quality. However, we currently lack an in-depth understanding of the relationship between particle characteristics and DPI product performance, and adequate quantitative relationships are not (yet) established. To be useful, any particle characterization tool for “engineered” particles is required to measure relevant parameters with sufficient accuracy, precision, sensitivity, and resolution. Therefore, how to justifiably select suitable characterization methods and establish appropriate specifications for key particle characteristics of pharmaceutical powders remains a challenge, not only for formulation and process development scientists in industry, but also for drug product reviewers ultimately responsible for product approval at the FDA. 

This presentation will overview various particle engineering techniques applicable to the manufacture of DPIs, and focus on scientific and regulatory considerations associated with the characterization and control of “engineered” particles for DPIs. It will also include a discussion of regulatory submission expectations with regard to characterization and control of critical particle characteristics of pharmaceutical powders for DPIs based on commonly seen deficiencies in new drug applications (NDAs) and abbreviated new drug applications (ANDAs). The objective of this presentation is to illustrate how to use a risk assessment approach as advocated by the quality by design (QbD) paradigm for developing particle characterization methods as well as establishing particle specifications for key dry powder properties of DPIs to ensure reproducible commercial manufacturing for consistent product quality.