Aggregate Analysis

Aggregate Analysis designates the comprehensive characterisation of protein aggregates in biopharmaceutical products spanning the full size range from small oligomers to visible particles, employing complementary analytical methods to detect, quantify, size, and characterise aggregate populations critical for patient safety and product quality assessment.

The biopharmaceutical industry conducts extensive aggregate analysis throughout biologic development as aggregates may trigger immunogenicity, reduce potency, or cause safety concerns. Size-exclusion chromatography quantifies soluble aggregates in the nanometre range. Dynamic light scattering and nanoparticle tracking analysis characterise submicron particles. Microflow imaging and light obscuration detect and count micron-scale particles. Visual inspection identifies visible particles. Analytical methods must collectively cover the entire aggregate size spectrum without gaps. Regulatory submissions include aggregate specifications with justification based on clinical and manufacturing data. As aggregate-related safety concerns receive increasing regulatory scrutiny, comprehensive aggregate analysis programmes continue expanding through improved analytical sensitivity and novel detection technologies.