Lyu X, Zhao Q, Hui J, Wang T, Lin M, Wang K, et al. The global landscape of approved antibody therapies. Antib Ther. 2022;5(4):233–57.

CAS  PubMed  PubMed Central  Google Scholar 

Walsh G, Walsh E. Biopharmaceutical benchmarks. Nat Biotechnol. 2022;2022:1–39.

Google Scholar 

Rathore AS, Chirmule N, Malani H. Reimagining affordable biosimilars. Biopharm Int. 2020;33(10):16–22.

Google Scholar 

Wang W, Roberts CJ. Protein aggregation—mechanisms, detection, and control. Int J Pharm. 2018;550(1–2):251–68.

Article  CAS  PubMed  Google Scholar 

Singla A, Bansal R, Joshi V, Rathore AS. Aggregation kinetics for IgG1-based monoclonal antibody therapeutics. AAPS J. 2016;18(3):689–702.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alt N, Zhang TY, Motchnik P, Taticek R, Quarmby V, Schlothauer T, et al. Determination of critical quality attributes for monoclonal antibodies using quality by design principles. Biologicals. 2016;44(5):291–305.

Article  CAS  PubMed  Google Scholar 

Eon-Duval A, Broly H, Gleixner R. Quality attributes of recombinant therapeutic proteins: an assessment of impact on safety and efficacy as part of a quality by design development approach. Biotechnol Prog. 2012;28(3):608–22.

Article  CAS  PubMed  Google Scholar 

Beck A, Liu H. Macro-and micro-heterogeneity of natural and recombinant IgG antibodies. Antibodies. 2019;8(1):18.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Singh SK, Kumar D, Rathore AS. Determination of critical quality attributes for a biotherapeutic in the QbD paradigm: GCSF as a case study. AAPS J. 2017;19:1826–41.

Article  CAS  PubMed  Google Scholar 

Bumbaca D, Boswell CA, Fielder PJ, Khawli LA. Physiochemical and biochemical factors influencing the pharmacokinetics of antibody therapeutics. AAPS J. 2012;14:554–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pham NB, Meng WS. Protein aggregation and immunogenicity of biotherapeutics. Int J Pharm. 2020;585: 119523.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rudge SR, Nims RW. ICH Q6B specifications: test procedures and acceptance criteria for biotechnological/biological products. ICH Quality Guidelines: An Implementation Guide. 2017;467–86.

Kayser V, Chennamsetty N, Voynov V, Helk B, Forrer K, Trout BL. Evaluation of a non-Arrhenius model for therapeutic monoclonal antibody aggregation. J Pharm Sci. 2011;100(7):2526–42.

Article  CAS  PubMed  Google Scholar 

Le Basle Y, Chennell P, Tokhadze N, Astier A, Sautou V. Physicochemical stability of monoclonal antibodies: a review. J Pharm Sci. 2020;109(1):169–90.

Article  PubMed  Google Scholar 

Kaur H. Stability testing in monoclonal antibodies. Crit Rev Biotechnol. 2021;41(5):692–714.

Article  CAS  PubMed  Google Scholar 

Vázquez-Rey M, Lang DA. Aggregates in monoclonal antibody manufacturing processes. Biotechnol Bioeng. 2011;108(7):1494–508.

Article  PubMed  Google Scholar 

Meyer RM, Berger L, Nerkamp J, Scheler S, Nehring S, Friess W. Identification of monoclonal antibody variants involved in aggregate formation—part 1: charge variants. Eur J Pharm Biopharm. 2021;158:123–31.

Article  CAS  PubMed  Google Scholar 

Meyer RM, Berger L, Nerkamp J, Scheler S, Nehring S, Friess W. Identification of monoclonal antibody variants involved in aggregate formation—part 2: hydrophobicity variants. Eur J Pharm Biopharm. 2021;160:134–42.

Article  CAS  PubMed  Google Scholar 

Courtois F, Agrawal NJ, Lauer TM, Trout BL. Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab. In: MAbs. Taylor & Francis; 2016;8(1):99–112.

Du Y, Walsh A, Ehrick R, Xu W, May K, Liu H. Chromatographic analysis of the acidic and basic species of recombinant monoclonal antibodies. In: MAbs. Taylor & Francis; 2012;4(5):578–85.

Yüce M, Sert F, Torabfam M, Parlar A, Gürel B, Çakır N, et al. Fractionated charge variants of biosimilars: a review of separation methods, structural and functional analysis. Anal Chim Acta. 2021;1152: 238189.

Article  PubMed  Google Scholar 

Beck A, Nowak C, Meshulam D, Reynolds K, Chen D, Pacardo DB, et al. Risk-based control strategies of recombinant monoclonal antibody charge variants. Antibodies. 2022;11(4):73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gervais D. Protein deamidation in biopharmaceutical manufacture: understanding, control and impact. J Chem Technol Biotechnol. 2016;91(3):569–75.

Article  CAS  Google Scholar 

Yan Q, Huang M, Lewis MJ, Hu P. Structure based prediction of asparagine deamidation propensity in monoclonal antibodies. In: MAbs. Taylor & Francis; 2018;10(6):901–12.

Alam ME, Barnett GV, Slaney TR, Starr CG, Das TK, Tessier PM. Deamidation can compromise antibody colloidal stability and enhance aggregation in a pH-dependent manner. Mol Pharm. 2019;16(5):1939–49.

Article  CAS  PubMed  Google Scholar 

Faid V, Leblanc Y, Berger M, Seifert A, Bihoreau N, Chevreux G. C-terminal lysine clipping of IgG1: impact on binding to human FcγRIIIa and neonatal Fc receptors. Eur J Pharm Sci. 2021;159: 105730.

Article  CAS  PubMed  Google Scholar 

Joshi VS, Kumar V, Rathore AS. Enhanced product understanding in the QbD paradigm: linkage between charge heterogeneity and stability of monoclonal antibody therapeutic products. J Chem Technol Biotechnol. 2018;93(8):2102–10.

Article  CAS  Google Scholar 

Spanov B, Olaleye O, Lingg N, Bentlage AEH, Govorukhina N, Hermans J, et al. Change of charge variant composition of trastuzumab upon stressing at physiological conditions. J Chromatogr A. 2021;1655: 462506.

Article  CAS  PubMed  Google Scholar 

Meyer RM, Aleshkevich S, Berger L, Nerkamp J, Scheler S, Friess W. Characterization of the aggregation propensity of charge variants of recombinant human growth hormone. Int J Pharm. 2022;621: 121760.

Article  CAS  PubMed  Google Scholar 

Joshi V, Shivach T, Kumar V, Yadav N, Rathore A. Avoiding antibody aggregation during processing: establishing hold times. Biotechnol J. 2014;9(9):1195–205.

Article  CAS  PubMed  Google Scholar 

Wälchli R, Vermeire PJ, Massant J, Arosio P. Accelerated aggregation studies of monoclonal antibodies: considerations for storage stability. J Pharm Sci. 2020;109(1):595–602.

Article  PubMed  Google Scholar 

Joshi S, Rathore AS. Assessment of structural and functional comparability of biosimilar products: trastuzumab as a case study. BioDrugs. 2020;34:209–23.

Article  CAS  PubMed  Google Scholar 

Singh SK, Kumar D, Malani H, Rathore AS. LC–MS based case-by-case analysis of the impact of acidic and basic charge variants of bevacizumab on stability and biological activity. Sci Rep. 2021;11(1):2487.

Levenspiel O. Chemical reaction engineering. John Wiley & Sons; 1998.

Shrivastava A, Mandal S, Pattanayek SK, Rathore AS. Rapid estimation of size-based heterogeneity in monoclonal antibodies by machine learning-enhanced dynamic light scattering. Anal Chem. 2023;95(21):8299–309.

Schmid I, Bonnington L, Gerl M, Bomans K, Thaller AL, Wagner K, et al. Assessment of susceptible chemical modification sites of trastuzumab and endogenous human immunoglobulins at physiological conditions. Commun Biol. 2018;1(1):28.

Article  PubMed  PubMed Central  Google Scholar 

Gupta S, Upadhyay K, Schöneich C, Rathore AS. Impact of various factors on the kinetics of non-enzymatic fragmentation of a monoclonal antibody. Eur J Pharm Biopharm. 2022;178:131–9.

Article  CAS  PubMed  Google Scholar 

Fincke A, Winter J, Bunte T, Olbrich C. Thermally induced degradation pathways of three different antibody-based drug development candidates. Eur J Pharm Sci. 2014;62:148–60.

Article  CAS  PubMed  Google Scholar 

Rajagopal K, Chang D, Nayak P, Izadi S, Patapoff T, Zhang J, et al. Trehalose limits fragment antibody aggregation and influences charge variant formation in spray-dried formulations at elevated temperatures. Mol Pharm. 2018;16(1):349–58.

Article  PubMed  Google Scholar 

Jaccoulet E, Daniel T, Prognon P, Caudron E. Forced degradation of monoclonal antibodies after compounding: impact on routine hospital quality control. J Pharm Sci. 2019;108(10):3252–61.

Article  CAS  PubMed  Google Scholar 

Shieh IC, Patel AR. Predicting the agitation-induced aggregation of monoclonal antibodies using surface tensiometry. Mol Pharm. 2015;12(9):3184–93.

Article  CAS  PubMed  Google Scholar 

Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, et al. Charge variants in IgG1: isolation, characterization, in vitro binding properties and pharmacokinetics in rats. MAbs. 2010;2(6):613–24.

Article  PubMed  PubMed Central  Google Scholar 

Singh SK, Kumar D, Nagpal S, Dubey SK, Rathore AS. A charge variant of bevacizumab offers enhanced FcRn-dependent pharmacokinetic half-life and efficacy. Pharm Res. 2022;39(5):851–65.

Article  CAS  PubMed  Google Scholar 

Singh SK, Narula G, Rathore AS. Should charge variants of monoclonal antibody therapeutics be considered critical quality attributes? Electroph