Subvisible Particles Are a Key Quality Metric for Biologic Drugs
Subvisible protein aggregates can form at any stage in the manufacturing process or during transportation and storage – triggered by oxidation, mechanical stress, impurities, pH shifts, temperature changes, device interface, etc.
Subvisible particles fall into a unique size range: too big for DLS, too big for SEC, and too small for visual analysis by eye.
Drug product formulation involves characterizing the processes for manufacture of the bulk formulation and final dosage form, stability and forced degradation studies, and interaction with primary packaging. Particles in protein drug formulations are often characterized by two common techniques a) light obscuration (LO) and b) flow imaging (FI). These flow-based systems consume significant sample from purging and dead volume, and have low throughput due to the washing and priming required to keep the flow cell clean and prevent sample-to-sample carryover.
The Aura™ and Horizon® systems are based on <USP 788> method of membrane microscopy – but automated. The method is completely reinvented using modern robotics, image processing, and novel optics technology. Since there are no fluidics on either system, it is easy to use, with no washing or priming, or risk of cross-contamination. Translucent particles can be clearly imaged, leading to more accurate particle counts.
The 96-well plate format consumes very little sample, which can be crucial when testing high concentration protein drug formulations.