ISSN: 2574-7797
Authors: Xiaobin Xu*
Fragmentation of therapeutic monoclonal antibodies (mAbs) is a critical quality attribute (CQA) that needs to be monitored and controlled during the biopharmaceutical drug development. Fragmentation of a protein is a result of either chemical or enzymatic reactions, leading to the cleavage of protein backbones. Fragmentation can occur through the entire mAb lifespan, from protein production in the bioreactor, purification process, storage, to blood circulation and clearance. Depending on the cleavage sites, fragmentation could affect the function of mAbs. The fragmentation occurred in the complementary determining regions (CDRs) can potentially impact on the binding of a mAb to its antigen, resulting in loss of efficacy; The fragmentation occurred in the Fragment crystallizable (Fc) region may influence on the binding to the Fc receptors and on the circulation half-time of the mAb; The fragmentation occurred in the hinge region can generate half-antibody,fragment antigen-binding (Fab) fragment, F(ab)’2 fragment, Fc fragment, Fc/2 fragment, or Fab-Fc fragment. Loss of one Fab arm may lead to reduced potency if the drug mechanism of action requires both Fab arms, such as bispecific mAbs. Loss of Fc region will be devoid of Fc receptor binding, reducing circulation half-time. In addition, fragmentation could correlate with the aggregation of mAbs [1]. The fragmentation pattern of a mAb not only reflects the intrinsic stability of a mAb rooted from protein engineering but also represents manufacture and process consistency, which is critical to ensure lot-to-lot product quality.
Keywords: mAbs; CQA; Fragment; C-termini analysis
