Characterization of Therapeutic Antibodies and Related Products

摘要

Here, we review the current state of the art in analytical and structural methods used to characterize therapeutic monoclonal antibodies (mAbs) and derivatives. First, a general introductive background on immunoglobulins G (IgGs) structures and microheterogeneities is presented. Then, the Review focuses on analytical papers published mainly the last two years. As a result, a compendium of dozens of microvariants, that have been identified for mAbs from both a separation sciences and a mass spectrometry perspective, is proposed. These small structural differences with the main IgG isoform include glycoforms, charge, cysteine-related, oxidized, size, and low level point mutation variants. In addition, the functional impact of these microvariants is discussed, helping their classification as low, medium, or high critical quality attributes (CQA) and contributing to the development of quality by design (QbD) paradigm. Then, analytical methods for higher order structures, mAb/antigens complexes, and aggregates are discussed. Finally, quantitative aspects are presented including mAbs quantification in biofluids and residual host cell proteins (HCPs).