LAUSR

Monoclonal antibodies hold a steadfast lead in the ever-expanding biologics marketplace and have revolutionized the treatment of a wide variety of illnesses. The prominence of mAbs as therapeutic agents brought with it the need for large scale production of these drugs, which in turn highlighted the need for improvements in cell culture processes to raise product titres. Increased product titres shifted bioprocessing concerns downstream as with increased titre brought along the increased expression of unwanted host cell proteins (HCPs). HCPs are a highly diverse range of proteins. While some HCPs can be degradative to the product itself, others could induce an unwanted immune response compromising the safety and efficacy of the biologic. Enzyme-linked immunosorbent assays (ELISAs) are currently the gold standard for release testing for HCPs. ELISAs provide quantitative measurement of total HCP levels but have several limitations. Industry has shifted towards the use of orthogonal methods to support process development and validation with a particular focus on analytical tools such as LC–MS/MS. This review discusses the current methods for identification and analysis of problematic HCPs in CHO cell lines used for mAb bioprocessing.