Recent Advances in Analysis of Protein Aggregation in Biopharmaceuticals

Protein drugs, represented by recombinant protein drugs and therapeutic antibodies, have become important components of biotech medicines. The efficacy and biosafety of protein drugs are superior to small molecule drugs in the treatment of serious diseases such as malignant tumor, autoimmune disease and virus infection. However, the stability of proteins is poor and they are prone to aggregate upon environmental stimulation or due to their own instability during the process of production, purification, transportation and storage. Protein aggregation may reduce therapeutic efficacy and thus induce immune responses. High. sensitivity, high-resolution, simple and practical techniques for protein aggregation detection are of great importance in the development and advancement of protein drugs. This paper intends to review the techniques used for protein aggregation analysis such as size-exclusion chromatography, gel-electrophoresis, analytical ultracentrifugation, field flow fractionation, turbidimetry/nephelometry, dynamic light scattering, nanoparticle tracking analysis, flow cytometry, and electron microscopy. The principle, strengths, limitations and applications of these techniques are discussed, and the direction in the future development is prospected.