Multivariate Modelling to Support Control Strategy Definition of Ellipta™ Combination Inhaled Products
Michelle Dawson1, Sandeep Sharma & Simeone Zomer
1GlaxoSmithKline R&D, Park Road, Ware, Herts, SG12 0DP, UK
Summary
The ELLIPTA™ dry powder inhaler, developed for the delivery of once daily therapies for the treatment of asthma and COPD, can hold one or two blister strips. The ability to accommodate two strips within the inhaler facilitates flexibility in formulation in that individual formulations can be developed in separate blister strips that can be combined flexibly to achieve different combination products.
The development of the Control Strategy for the Aerodynamic Particle Size Distribution (APSD) of the emitted dose has been supported by multivariate modelling to comprehensively assess the variability in APSD undersize cuts (i.e. deposition stages from the Next Generation Impactor) and their potential relationship to material attributes and process parameters investigated and/or routinely recorded during development activities.
This paper describes how multivariate modelling was adopted to underpin definition of the Control Strategy for a drug product formulation used in different products. First, Principal Components Analysis was used to determine typical patterns of variation in APSD undersize cuts, and demonstrate that the same drug substance within the two products exhibited highly comparable patterns. Secondly, Multivariate Regression was used to examine the correlations of a number of material attributes and process parameters with Fine Particle Mass (FPMass) and other grouped stages within the APSD profile. Results showed highly comparable outcomes across the two products, where the strongest correlations to FPMass were identified for two classes of independently assigned Critical Quality Attributes. Periodic multivariate modelling helped direct ongoing development and provided confirmation on the adoption of the same Control Strategy for a common drug substance component in different products.
