)
Liquid chromatography-mass spectrometry multiple attribute monitoring (LC-MS MAM) to provide primary structure/post-translational modification data
Surface plasmon resonance (SPR) ligand binding to provide structure/function data
Reduced analytical workflows of standard methods of size exclusion chromatography coupled with multiple-angle light scattering (SEC-MALS), total soluble protein determination and dynamic light scattering (DLS) to understand colloidal/conformational stability, oligomerization, and aggregation
pH screen to evaluate colloidal and confirmational stability for optimal pH conditions. The optimal pH is then incorporated into the experimental testing of selected well-established excipients
To further streamline the study, in line with ICH Q8 (R2) and QbD, our process incorporates a design of experiment (DoE) statistical approach to evaluate the potential of stabilizing excipients when exposed to thermal stress. Using DoE provides the maximum amount of data for the minimum number of samples and hence also reduces the analytical load. The outcome of these studies is a lead formulation for subsequent additional stability testing, such as real-time, accelerated and/or forced degradation.
