The application of biological product analytical methodologies to support the development of biologic dry powder inhalation products

Karen Western, Nick Childerhouse, Sandy Munro, Sara Sefton

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 fine particle mass). One of the biggest challenges is ensuring that biologic potency and purity is maintained during the various manufacturing processes and afterwards, throughout the product shelf life and during drug delivery through the DPI. The application of a content assay method during development of a spray dried cytokine powder product identified that stabilising excipients were required in the feedstock to protect the cytokine from shear forces during spray drying. Development of a powder matrix for an immunomodulatory peptide required use of a purity (size exclusion chromatography (SEC)) method to detect degradation because a measure of activity alone by enzyme-linked immunosorbent assay (ELISA) would not have differentiated between different the stabilising properties of the powder matrices. A further case study for an immunomodulatory protein demonstrated how two different purity methods (SEC and non-reducing sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)) may be required to detect aggregation. The final case study demonstrated how, during development pharmaceutics type studies to assess the DPI delivery system, the use of methods to both quantify biologic deposits on the device and assess the stability of these deposits using a biologic product analytical method to determine purity, provided information on formulation and delivery device optimisation. These investigations demonstrate how orthogonal biological product analytical methods have aided formulation/product development, manufacturing feasibility and product stability for potential biologic DPI products.

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