(778c) Quality By Design Approaches for Dry Powder Inhalation Products: A Regulatory Perspective

FDA has advocated companies to implement Quality by Design (QbD) into product lifecycles, with particular emphasis during product development. The goal of this presentation is to discuss the benefit and advantage the QbD approach brings to the design and manufacture of orally inhaled drug product, specifically the dry powder inhaler (DPI) variety. Since DPI is also a combination product, its successful development requires thorough understanding of the complex interaction between the powder formulation and the delivery device. We will illustrate how the QbD paradigm can aid in this process through case studies, including device-metered (reservoir) DPI and pre-metered (blister) DPI. We will start by identifying some key Quality Target Product Profile as well as Critical Quality Attributes (CQA). Through risk assessment and experimentation during development, Critical Material Attributes and Critical Process Parameters can be linked to the CQAs, thus allowing the design and implementation of an adequate control strategy, and reducing the need of intensive in-process testing. This is critical for DPI manufacturing since the standard assessment methods (Aerodynamic Particle Size Distribution and Delivered Dose Content Uniformity) have low testing efficiency. We will conclude with a discussion of regulatory submission expectations with respect to in-process control strategy based on commonly seen deficiencies in New Drug Applications and Abbreviated New Drug Applications.