Analytical method development and validation is performed using a generic Quality by Design (QbD) framework for Life Cycle Management. This is analogous to the framework recommended for product development in ICH guidelines. All methodology has a defined Analytical Target Profile (ATP), a set of predefined objectives that defines performance requirements, and are subject to risk management and continuous improvement processes.
The methodology for uniformity of delivered dose (UoDD), or dose content uniformity (DCU), is a Critical Quality Attribute (CQA) of Orally Inhaled and Nasal Drug Products (OINDP). In line with the QbD paradigm, this critical variable was assessed by designed experiments to understand the performance of the SirduplaTM generic product versus the Seretide® Evohaler® innovator product (Salmeterol / Fluticasone Propionate, 120 actuations).
The analytical method requires control of critical shake / fire parameters for the priming, dose collection and waste actuations. In this case the priming and dose collection actuations are performed by an analyst. Automation is used only for the waste actuations performed between the stages of container life where the dose collection actuations are performed. Automation could be extended to the priming/collection actuations, and even the sample recovery process, to exercise greater control. The optimised methodology demonstrates that the SirduplaTM pMDI (pressurised Metered Dose Inhaler) product generates comparable UoDD data to the Seretide® Evohaler® innovator product. Method robustness can therefore be established at an early stage in the method and product development life cycle, delivering methodology demonstrably appropriate for the product lifespan which is subject to continuous improvement processes in line with the QbD paradigm.