As monoclonal antibody and recombinant protein drugs are becoming the fastest growing sectors of the pharmaceutical industry, careful inspection of the complete product properties (e.g., purity, biochemical properties, and stability) is critical throughout development and manufacturing. This is especially the case with antibodies which are often heterogeneous in nature.
Furthermore, antibodies’ various post-translational modifications (PTMs) (Figure 2) may occur over the molecule’s lifecycle. PTMs play significant contributions to antigen-binding, folding, and biological function of antibodies, consequently and directly impacting drug efficacy, stability, and safety. For example, glycosylation, one of the most common PTMs in antibodies, plays an important role in regulating many drug side effects including antibody-dependent cellular cytotoxicity and phagocytosis.
In addition to PTMs, other artifacts (e.g., aggregation, degradation, and contamination) which contribute to antibody heterogeneity can also be introduced during manufacturing and long-term storage. The latter may not only gravely impact manufacturing, but may also result in severe immunogenicity during antibody drug administration to patients.
Figure 2. Infographics showing types of antibody heterogeneity that can be analyzed by peptide mapping