Liquid chromatography–fluorescence and liquid chromatography–mass spectrometry detection of tryptophan degradation products of a recombinant monoclonal antibody

Nowak, Christine; Ponniah, Gomathinayagam; Cheng, Guilong; Kita, Adriana; Neill, Alyssa; Kori, Yekaterina; Liu, Hongcheng

doi:10.1016/j.ab.2015.12.004

Cited by 9 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…63 Light exposure resulting in fragmentation around the hinge region has also been commonly observed. 62,63 As expected, several residues including tryptophan, [62][63][64][65] methionine, 33,62,63,65,66 and histidine 63 are highly sensitive and become oxidized from light exposure. Oxidation of tryptophan residues results in the formation of a variety of products, with the major products having molecular weight increases of 16 Da and 32 Da.…”

Section: High Ph and Forced Deamidationsupporting

confidence: 57%

Forced degradation of recombinant monoclonal antibodies: A practical guide

Nowak

Cheung

Dellatore

et al. 2017

mAbs

Self Cite

188

150

View full text Add to dashboard Cite

Forced degradation studies have become integral to the development of recombinant monoclonal antibody therapeutics by serving a variety of objectives from early stage manufacturability evaluation to supporting comparability assessments both pre- and post- marketing approval. This review summarizes the regulatory guidance scattered throughout different documents to highlight the expectations from various agencies such as the Food and Drug Administration and European Medicines Agency. The various purposes for forced degradation studies, commonly used conditions and the major degradation pathways under each condition are also discussed.

show abstract

Section: High Ph and Forced Deamidationsupporting

confidence: 57%

Forced degradation of recombinant monoclonal antibodies: A practical guide

Nowak

Cheung

Dellatore

et al. 2017

mAbs

Self Cite

188

150

View full text Add to dashboard Cite

show abstract

“…Oxidation has also been observed at tryptophan (Trp) residues in mAbs [59,60,61,62]. Trp residues in CDRs are more susceptible to oxidation due to a higher level of solvent exposure [63].…”

Section: Oxidationmentioning

confidence: 99%

“…Trp residues in CDRs are more susceptible to oxidation due to a higher level of solvent exposure [63]. Oxidation of Trp generates a number of species, the major ones having molecular weight increases of 16 Da, and 32 Da [62,64]. MAb variants with oxidized Trp are less hydrophobic [52].…”

Section: Oxidationmentioning

confidence: 99%

Macro- and Micro-Heterogeneity of Natural and Recombinant IgG Antibodies

Beck

Liu²

2019

Antibodies

Self Cite

View full text Add to dashboard Cite

Recombinant monoclonal antibodies (mAbs) intended for therapeutic usage are required to be thoroughly characterized, which has promoted an extensive effort towards the understanding of the structures and heterogeneity of this major class of molecules. Batch consistency and comparability are highly relevant to the successful pharmaceutical development of mAbs and related products. Small structural modifications that contribute to molecule variants (or proteoforms) differing in size, charge or hydrophobicity have been identified. These modifications may impact (or not) the stability, pharmacokinetics, and efficacy of mAbs. The presence of the same type of modifications as found in endogenous immunoglobulin G (IgG) can substantially lower the safety risks of mAbs. The knowledge of modifications is also critical to the ranking of critical quality attributes (CQAs) of the drug and define the Quality Target Product Profile (QTPP). This review provides a summary of the current understanding of post-translational and physico-chemical modifications identified in recombinant mAbs and endogenous IgGs at physiological conditions.

show abstract