Charge variants characterization and release assay development for co-formulated antibodies as a combination therapy. Issue 3 (3rd April 2019)

• Record Type: Journal Article
• Authors: Cao, Mingyan; De Mel, Niluka; Shannon, Anthony; Prophet, Meagan; Wang, Chunlei; Xu, Weichen; Niu, Ben; Kim, Jun; Albarghouthi, Methal; Liu, Dengfeng; Meinke, Eric; Lin, Shihua; Wang, Xiangyang; Wang, Jihong
• Is Part Of: MAbs. Volume 11:Issue 3(2019)
• Page Start: 489
• Page End: 499
• Publication Date: 2019-04-03
• Subjects: Immunotherapy -- monoclonal antibody -- combination therapy -- co-formulated combination antibodies charge variant -- critical quality attribute -- complementarity-determining regions -- deamidation -- focused peptide mapping -- multi-attribute method; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2019.1578137
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: Combination therapy is a fast-growing strategy to maximize therapeutic benefits to patients. Co-formulation of two or more therapeutic proteins has advantages over the administration of multiple medications, including reduced medication errors and convenience for patients. Characterization of co-formulated biologics can be challenging due to the high degree of similarity in the physicochemical properties of co-formulated proteins, especially at different concentrations of individual components. We present the results of a deamidation study of one monoclonal antibody component (mAb-B) in co-formulated combination antibodies (referred to as COMBO) that contain various ratios of mAb-A and mAb-B. A single deamidation site in the complementarity-determining region of mAb-B was identified as a critical quality attribute (CQA) due to its impact on biological activity. A conventional charge-based method of monitoring mAb-B deamidation presented specificity and robustness challenges, especially when mAb-B was a minor component in the COMBO, making it unsuitable for lot release and stability testing. We developed and qualified a new, quality-control-friendly, single quadrupole Dalton mass detector (QDa)–based method to monitor site-specific deamidation. Our approach can be also used as a multi-attribute method for monitoring other quality attributes in COMBO. This analytical paradigm is applicable to the identification of CQAs in combination therapeutic molecules, and to the subsequent development of a highly specific, highly sensitive, and sufficiently robust method for routine monitoring CQAs for lot release test and during stability studies.