Effect of ambient light on IgG1 monoclonal antibodies during drug product processing and development

Sreedhara, Alavattam; Yin, Jian; Joyce, Michael; Lau, Kimberly S. F.; Wecksler, Aaron T.; Deperalta, Galahad; Li, Yi; Wang, Y. John; Kabakoff, Bruce; Kishore, Ravuri S. K.

doi:10.1016/j.ejpb.2015.12.003

Cited by 77 publications

(48 citation statements)

References 29 publications

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“…As such, the authors conclude that ambient light stability studies would be more relevant stress models than ICH conditions for mAb photostability testing. 111 Luis et al assessed the photostability of 2 mAbs through both the ICH Q1B recommendations (1.32 million lux hours) and custom ambient light exposure assays (0.24 million lux hours), and exhibited drastic differences concerning mAbs degradation. They also showed that mAbs photostability depends on the overall amount of light exposure rather than light intensity.…”

Section: Interfacesmentioning

confidence: 99%

Physicochemical Stability of Monoclonal Antibodies: A Review

Basle

Chennell

Tokhadzé

et al. 2020

Journal of Pharmaceutical Sciences

294

162

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Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.

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Section: Interfacesmentioning

confidence: 99%

Physicochemical Stability of Monoclonal Antibodies: A Review

Basle

Chennell

Tokhadzé

et al. 2020

Journal of Pharmaceutical Sciences

294

162

View full text Add to dashboard Cite

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“…230,231 Oxidation of Trp could account for coloration of mAbs after exposure to heat and especially light. 138,178,221,232 The quality of polysorbate has a substantial impact on mAb photostability, 222 but its direct contribution to coloration at the time of release is minimal because of its low concentration. However, differences in polysorbate quality may become visible during forced degradation studies.…”

Section: Colorationmentioning

confidence: 99%

Analytical comparability study of recombinant monoclonal antibody therapeutics

Ambrogelly

Gozo²,

Katiyar

et al. 2018

mAbs

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Process changes are inevitable in the life cycle of recombinant monoclonal antibody therapeutics. Products made using pre- and post-change processes are required to be comparable as demonstrated by comparability studies to qualify for continuous development and commercial supply. Establishment of comparability is a systematic process of gathering and evaluating data based on scientific understanding and clinical experience of the relationship between product quality attributes and their impact on safety and efficacy. This review summarizes the current understanding of various modifications of recombinant monoclonal antibodies. It further outlines the critical steps in designing and executing successful comparability studies to support process changes at different stages of a product's lifecycle.

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“…In fact, the UV light‐induced oxidation of Trp 105 in the complementary‐determining region (CDR) of the heavy chain of a humanized monoclonal antibody resulted in loss of biological activity . Importantly, Trp photooxidation was also detected when a monoclonal antibody was exposed to ambient light . It has been recognized that surface exposure represents one important parameter controlling Trp oxidation and photooxidation in monoclonal antibodies.…”

Section: Introductionmentioning

confidence: 99%

Novel chemical degradation pathways of proteins mediated by tryptophan oxidation: tryptophan side chain fragmentation

Schöneich

2018

Journal of Pharmacy and Pharmacology

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Objectives This minireview focuses on novel degradation pathways of proteins in solution via intermediary tryptophan (Trp) radical cations, which are generated via photo-induced electron transfer to suitable acceptors such as disulfide bonds. Methods Gas-phase mass spectrometry studies had indicated the potential for Trp radical cations to fragment via release of 3-methylene-3H-indol-1-ium from the side chain. HPLC-MS/MS analysis demonstrates that analogous fragmentation reactions occur during the exposure of peptides and proteins to light or accelerated stability testing. Key findings The light exposure of selected peptides and monoclonal antibodies leads to the conversion of Trp to glycine (Gly) or glycine hydroperoxide (GlyOOH), where GlyOOH could be reduced to hydroxyglycine, which undergoes subsequent cleavage. Product formation is consistent with C a -C b fragmentation of intermediary Trp radical cations. For the peptide octreotide and specific glycoforms of IgG1 Fc domains, Trp side chain cleavage in aqueous solution is indicated by the formation of 3-methyleneindolenine (3-MEI), which adds to nucleophilic side chains, for example to Lys residues adjacent to the original Trp residues. Conclusions Trp side chain cleavage leads to novel reaction products on specific peptide and protein sequences, which may have consequences for potency and immunogenicity.

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Effect of ambient light on IgG1 monoclonal antibodies during drug product processing and development

Cited by 77 publications

References 29 publications

Physicochemical Stability of Monoclonal Antibodies: A Review

Physicochemical Stability of Monoclonal Antibodies: A Review

Analytical comparability study of recombinant monoclonal antibody therapeutics

Novel chemical degradation pathways of proteins mediated by tryptophan oxidation: tryptophan side chain fragmentation

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