title: Should charge variants of monoclonal antibody therapeutics be considered critical quality attributes?
abstract: Charge variants, namely acidic and basic variants, are typically found in mAb therapeutics. Charge heterogeneity is typically not regarded to affect safety and efficacy of the product. As a result, the commonly followed approach involves assignment of a specification for the variants based on statistical analysis of variability in levels that is seen during commercial manufacturing. This is followed by monitoring of product quality to demonstrate consistency. This paper aims to demonstrate that this perception of charge variants warrants a more in-depth investigation to evaluate the role charge variants play in safety and efficacy of a mAb therapeutic. In addition, a novel procedure has been suggested for making this assessment and alleviate the problems that are traditionally faced when isolating these variants for characterization. The suggested procedure utilizes the principles of bioseparations, cell biology, and statistics and it is demonstrated that this is significantly more efficient than the approach practiced today.
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India.
authors.forename: Sumit Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Narula
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India. asrathore@biotechcmz.com.
authors.forename: Anurag S
authors.initials: AS
authors.lastname: Rathore
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D002460:Cell Line; D049109:Cell Proliferation; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D013058:Mass Spectrometry
chemical_list: D000911:Antibodies, Monoclonal
keywords: Cell-based assay; Charge variants; Critical quality attributes; Monoclonal antibodies; Statistical modeling