Quantifying and sizing subvisible particles in biopharmaceutical products are crucial aspects of formulation development, stability studies, process development, product release and extended characterisation of the final drug product. The particles, which may consist of aggregated proteins, and/or components shed from process materials or container closure systems, can directly impact on the efficacy and immunogenicity of a drug product. They often act as nucleation sites for further protein aggregation and/or lead to the development of larger particles by agglomeration. Measuring the size and concentration of subvisible particles within a formulation is an essential precursor to their effective control, and of growing importance as the industry works towards ‘zero defect’ and ‘essentially particle-free’ products. This article considers requirements for subvisible particle measurement within the context of current regulatory expectations, and more broadly, review the technology available to meet them.
Formulation development; Protein aggregation; Subdivisible particle sizing; Particle-free products