The effect of sucrose hydrolysis on the stability of protein therapeutics during accelerated formulation studies

Banks, Douglas D.; Hambly, David M.; Scavezze, Joanna L.; Siska, Christine C.; Stackhouse, Nicole; Gadgil, Himanshu S.

doi:10.1002/jps.21749

Cited by 78 publications

(57 citation statements)

References 18 publications

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“…Stability data from studies using formulation stored at 4-5 C for up to 21/months showed a minimal or low to no increase in the level of glycation. 32,34,35 The same formulations stored at elevated temperatures from 29 to 37 C for 1-21/months showed significant increases in glycation levels. Based on these observations, the use of accelerated stability data are of questionable value for predicting protein stability in sucrosecontaining formulations stored at 2-8 C, where little or no glycation was observed.…”

Section: Causes Of Therapeutic Antibody Glycationmentioning

confidence: 94%

“…Modification increased with increased storage temperature from 5 C to 30 C. Banks, et al 32,72 Sucrose, IgG1 and IgG2 monoclonal antibodies mAb001 at 100 mg/mL formulated with either 270 mM sucrose, 270 mM sorbitol, or no excipient and buffered at pH 5.2 with 10 mM sodium acetate and pH 4.8 with 10 mM sodium lactate…”

Section: Charge-based Methodsmentioning

confidence: 99%

“…21 Antibody aggregation is an important CQA related to immunogenicity and safety. Reports correlating glycation levels with aggregation have been inconsistent, with one study showing a correlation, 32 but another indicating that there was no significant difference in the level of aggregation observed between glycated and control mAb stored at 40 C for 1/week. 40 The detailed mechanism of glycation-induced protein aggregation remains unclear.…”

Section: Effects On Biological Functionmentioning

confidence: 99%

“…The acidic pH and elevated temperature can cause accelerated sucrose hydrolysis, leading to the production of reducing sugars and subsequent glycation. 32,33 The speed of the Maillard reaction also depends on formulation buffer salt components and the type of sugar in the formulation buffers. Nevertheless, the overall glycation rate in optimized storage conditions is minimal to none.…”

Section: Causes Of Therapeutic Antibody Glycationmentioning

confidence: 99%

“…Based on these observations, the use of accelerated stability data are of questionable value for predicting protein stability in sucrosecontaining formulations stored at 2-8 C, where little or no glycation was observed. 32 The results of studies on antibody glycation during storage are summarized in Table 1.…”

Section: Causes Of Therapeutic Antibody Glycationmentioning

confidence: 99%

See 4 more Smart Citations

Glycation of antibodies: Modification, methods and potential effects on biological functions

Wei¹,

Berning²,

Quan³

et al. 2017

mAbs

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Glycation is an important protein modification that could potentially affect bioactivity and molecular stability, and glycation of therapeutic proteins such as monoclonal antibodies should be well characterized. Glycated protein could undergo further degradation into advance glycation end (AGE) products. Here, we review the root cause of glycation during the manufacturing, storage and in vivo circulation of therapeutic antibodies, and the current analytical methods used to detect and characterize glycation and AGEs, including boronate affinity chromatography, charge-based methods, liquid chromatography-mass spectrometry and colorimetric assay. The biological effects of therapeutic protein glycation and AGEs, which ranged from no affect to loss of activity, are also discussed.

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Section: Causes Of Therapeutic Antibody Glycationmentioning

confidence: 94%

Section: Charge-based Methodsmentioning

confidence: 99%

Section: Effects On Biological Functionmentioning

confidence: 99%

Section: Causes Of Therapeutic Antibody Glycationmentioning

confidence: 99%

Section: Causes Of Therapeutic Antibody Glycationmentioning

confidence: 99%

See 3 more Smart Citations

Glycation of antibodies: Modification, methods and potential effects on biological functions

Wei¹,

Berning²,

Quan³

et al. 2017

mAbs

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Process Development of Protein Therapeutics

Huang¹,

Bowes²,

Yang³

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The application of recombinant DNA technology to the production of protein therapeutics has undergone tremendous progress over the past decades. Considerable scientific effort has been devoted to developing robust processes that produce large amounts of complex proteins with the desired product quality attributes. An overview of the contributions from the four major disciplines working in concert to deliver these processes and methods will be covered. This article will discuss some of the tools, methods, and approaches used to produce, purify, formulate, and analyze the drugs of modern biotechnology. Future trends in each of the disciplines will also be presented.

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Identification and Quantification of Degradants and Impurities in Antibodies

Hambly

Gadgil

2011

Characterization of Impurities and Degradants Using Mass Spectrometry

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The effect of sucrose hydrolysis on the stability of protein therapeutics during accelerated formulation studies

Cited by 78 publications

References 18 publications

Glycation of antibodies: Modification, methods and potential effects on biological functions

Glycation of antibodies: Modification, methods and potential effects on biological functions

Process Development of Protein Therapeutics

Identification and Quantification of Degradants and Impurities in Antibodies

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