All therapeutic protein products contain particles formed by the aggregation of protein monomers. There is a growing interest in the understanding of particles in biopharmaceutical products, which has been fostered on the one hand by significant advancements in the development of novel technologies for particle analysis and on the other hand by concerns about potential impact of particles on product quality and safety. With currently available analytical methods, particles in therapeutic proteins can be counted, sized, and characterized in a rudimentary way over a broad size range (effective diameters from 10s of nanometers to 100s of micrometers) with a high level of sensitivity. We review the known attributes of common protein particles, and then discuss the gaps in our knowledge. The capabilities, limitations, and opportunities for improvement of common particle counting and characterization methods are listed. Further analytical progress is needed to better classify and characterize the great diversity of particles encountered in pharmaceutical products, which may vary in the degree of protein unfolding, the inclusion of non-protein nucleation centers, and aggregate morphology. Very little is known about potential correlation between particles and increased immunogenicity. Under the environment of uncertainty the understanding about specific particle attributes and potentially increased immunogenicity is greatly needed and will likely be an area of intensive research in the coming years.
Citation: Journal of Pharmaceutical Sciences
Pub Type: Journals
aggregates, particle, particle counter, protein