Monoclonal antibodies (mAbs) represent the most important group of protein-based biopharmaceuticals. Like all the other protein therapeutics, mAb can undergo various degradation processes during production, formulation, storage, transport, etc. The presence of aggregates is undesirable because they can lead to activity loss, decreased solubility, and enhanced unwanted immunogenicity. During the development and production of mAb therapeutics, it is essential to characterize mAb aggregates for process monitoring and quality control.
With years of experience in therapeutic antibody development, Creative Biolabs offers extensive analytical services to help our clients get an in-depth understanding of their therapeutic mAb candidates in terms of their physicochemical properties, bioactivity, affinity, and purity. Here, we introduce mAb aggregation analysis as part of our antibody characterization and analysis service portfolio.
Protein aggregation denotes the processes by which protein molecules assemble into stable complexes composed of two or more proteins, with the individual proteins denoted as the monomer. mAbs have been shown to aggregate under a wide variety of conditions and through various pathways. Firstly, during the protein folding process, mAbs can aggregate via partial unfolding or misfolding because the exposed hydrophobic regions tend to form a more stable energy state by binding to each other. Secondly, during formulation, manufacturing, or storage, antibodies can suffer modifications that alter their physical and chemical properties, leading to conformational changes and the formation of aggregates. For instance, mAbs can form covalent aggregates via disulfide bond formation from the presences of exposed free thiol groups. Thirdly, aggregation can occur through self-association due to the electrostatic and hydrophobic interactions between molecules, which do not need an unfolding or misfolding intermediate to aggregate. For instance, high concentration formulations of mAbs increase the propensity to aggregate. For different pathways, mAb aggregates arise in different forms including reversible non-covalent, irreversible non-covalent, and irreversible covalent species. The size of these aggregates varies from a few nanometers to hundreds of microns, affecting the biological properties of mAbs.
Fig.1 Schematic diagram illustrating multiple aggregation pathways for a monoclonal antibody. (Roberts, 2014)
Aggregation characterization is key to successful biopharmaceutical development and manufacturing. Assessing or analyzing the aggregation level of mAb therapeutic candidates is a regulatory requirement and also an important component of developability assessment. Experts at Creative Biolabs can apply a range of analytical tools to detect and quantify aggregates at different stages of mAb development and manufacturing.
Through our unique level of expertise and advanced techniques, Creative Biolabs is confident in providing the most comprehensive analytical services to satisfy your antibody aggregation analysis needs. If you are interested in our service, please contact us to discuss your requirements.
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