Analysis of Aggregates and Particles

Abstract

Biologics subjected to interfacial stress can generate a diverse assortment of aggregated species ranging in size from dimers and other soluble aggregates, through subvisible or micrometer-sized particles, to particles in the hundreds of micrometers that are visible to the unaided eye. The quantification and analysis of these aggregates are an important aspect in assessing, characterizing, and mitigating product changes due to interfacial stress. An analytical and characterization strategy needs to be developed that utilizes techniques that provide insight into the composition, morphology, mechanism of formation, and quantitation (e.g., mass, particle count) of the aggregated species. To date, no single analytical technique is capable of providing such a comprehensive assessment of the variety of aggregates that can be generated by interfacial stress. The subsequent section presents an overview of the analytical tools useful for characterizing aggregated species, including techniques that assess secondary/tertiary/higher-order structure, size, and morphology, and will discuss established techniques as well as emerging new technologies for extended characterization.