Biopurification of monoclonal antibody (mAb) through crystallisation

• Main Authors: Chen, WQ (Author), Guo, MX (Author), Heng, JYY (Author), Li, XY (Author), Link, FJ (Author), Ouyang, JB (Author), Ramli, SS (Author), Rosbottom, I (Author)
• Format: Article
• Language: English
• Published: 2021
• Subjects: Biopurification; EGG-WHITE; HETEROGENEOUS NUCLEATION; HOFMEISTER SERIES; HOST-CELL PROTEIN; HUMAN-IGG; LIQUID-PHASE-SEPARATION; Monoclonal antibody; Phase behaviour; POLISHING STEPS; PROTEIN CRYSTAL NUCLEATION; Protein crystallisation; Scale-up; SUPERSATURATED LYSOZYME SOLUTIONS; SURFACE-CHEMISTRY
• Online Access: View Fulltext in Publisher

 Therapeutics based on monoclonal antibody (mAb) represent the most advanced biopharmaceuticals, being able to treat a wide range of challenging diseases such as cancers and arthritis. As the scale of mAb production steadily increases with the demand for mAb-based therapeutics, the downstream biopurification continues to experience significant bottleneck due to the throughput limited nature of the current purification technology. Over the last decades, significant advances have been made in protein (and especially mAb) crystallisation as an alternative biopurification technology that offers high product stability and purity as well as scalability. This review starts with the discussion of general physicochemical properties of mAb before moving on to the in-depth discussion of the distinct phase behaviour of mAb in comparison with conventional globular proteins such as lysozyme. The final part of this review presents a summary of successful demonstrations of crystallisation scale-ups of mAb and discusses the critical factors (i.e. mixing and temperature control) to be considered.