Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms.

Abstract:

:As part of a series of articles in this special issue evaluating model IgG1-Fc glycoforms for biosimilarity analysis, 3 well-defined IgG1-Fc glycoforms (high mannose-Fc, Man5-Fc, and N-acetylglucosamine-Fc) and a nonglycosylated Fc protein (N297Q-Fc) were examined in this work to elucidate chemical degradation pathways. The 4 proteins underwent a combination of accelerated thermal stability studies and 4 independent forced degradation studies (UV light, metal-catalyzed oxidation, peroxyl radicals, and hydrogen peroxide) at pH 6.0. Our results highlight chemical degradations at Asn315, Met428, Trp277, and Trp313. A cross-comparison of the different Fc glycoforms, stress conditions, and the observed chemical reactions revealed that both the deamidation of Asn315 and the transformation of Trp277 into glycine hydroperoxide were glycan dependent during incubation for 3 months at 40 °C. Our data will show that different glycans not only affect chemical degradation differently but also do lead to different impurity profiles, which can affect chemical degradation.

journal_name

J Pharm Sci

authors

Mozziconacci O,Okbazghi S,More AS,Volkin DB,Tolbert T,Schöneich C

doi

10.1016/j.xphs.2015.10.024

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

575-587

issue

2

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)00025-8

journal_volume

105

pub_type

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