Chapter 11: Particles in Biopharmaceuticals: Causes, Characterization, and Strategy

An Interlaboratory Comparison on the Characterization of a Sub-micrometer Polydisperse Particle Dispersion

“…that differ in density and refractive index. 8,11 Given that the sample was predominantly composed of PMMA spheres, it was recommended that participants use the PMMA density for converting RMM data to size. As noted above in the experimental section, the silica may influence particle counts with a peak at % 0.35 mm, with the peak shift observed in the averaged RMM data, but not in all individual plots (Figs.…”

“…The range from 0.1 mm to 1 mm can be further classified as a sub-micrometer size regime; this range is of particular interest in the biopharmaceutical field for understanding the aggregation of the therapeutic proteins and potential implications on immunogenicity. 2,[7][8][9][10] Identifying non-proteinaceous particles in the sub-micrometer size regime (e.g., silicone oil droplets, steel or other intrinsic materials related to therapeutic processing and extrinsic materials) is also of interest, 7,11 while other types of samples have similar challenges and interests (e.g., hydrocolloids and food structures, drug and vaccine delivery systems, or extracellular vesicles). [12][13][14][15] Particles with sizes (equivalent diameters) below % 1 mm are particularly challenging to count and size, given the cutoff for typical optical flow imaging and light obscuration analysis tools.…”

A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

“…Therefore, to enable therapeutic use of HCAPs, they must be formulated, stabilized, developed, and manufactured using robust processes. The art and science of antibody formulation and stabilization evolves over time, and several reviews 6 , 8–12 and books 13–16 have described the basic concepts in antibody drug product formulation development and manufacturing. 17 , 18 Other reviews have highlighted issues associated with protein aggregation, including possible mechanisms and how manufacturing processes for antibody drug products should be designed to overcome these challenges.…”

Imaging Flow Cytometry for Sizing and Counting of Subvisible Particles in Biotherapeutics

“…9 In addition to size and concentration, the identification of origin and material composition are further important aspects in the characterization of particles. 10,11 Besides protein particles, non-proteinaceous sources for particles in biopharmaceuticals can for example be silicone oil (SO) droplets released from the lubrication of glass syringe barrels or from rubber closures. 12,13 Overall, particle classification can provide information on potential health risks and can give hints on countermeasures to reduce particle levels in biopharmaceutical products.…”

“…12,13 Overall, particle classification can provide information on potential health risks and can give hints on countermeasures to reduce particle levels in biopharmaceutical products. 10,11 Imaging flow cytometry (IFC), a technique originally designed for cytometry applications, was introduced to the field of particle analysis about ten years ago. 14 IFC aims at the extension of classic brightfield-based particle characterization as, e.g., in flow imaging microscopy (FIM), by additional imaging options in side scattering (SSC) and fluorescence (FL) channels.…”