Summary

The development of a biologic as a dry powder inhaler (DPI) product presents additional challenges to those already typically anticipated for a small molecule DPI (e.g. consistent and stable emitted dose (ED) and Aerodynamic Particle Size Distribution of the Emitted Dose (APSDED) [1, 2]. In addition to these requirements, one of the biggest challenges is ensuring that biologic potency and integrity is maintained during drug delivery through the DPI. An immunomodulatory peptide has been formulated into a DPI which is intended for multiple-use with prefilled unit-dose blisters. Patient simulation studies have demonstrated consistent aerosol performance (ED and APSDED) when multiple doses are delivered through the DPI over consecutive days. A build-up of device deposition and device associated protein aggregates was observed as dose number increased. This is considered a potential risk to consistent drug delivery of consecutive doses as there is potential for deposited formulation to dislodge and entrain in the airflow of subsequent doses. It is also a risk for patient safety where inhalation of protein aggregates could illicit an immune response in patients. Whilst a degree of inhaler deposition was evident, the aerosol performance of the formulation remained consistent over consecutive delivered doses. This demonstrates that the therapeutic target dose is not impacted by multiple use of the inhaler. Furthermore, protein aggregates deposited on the inhaler were not detected within subsequent delivered doses. Developing methodology to track this is pivotal for patient safety and therapeutic efficacy of the immunomodulatory peptide when delivered through a multiple-use DPI.