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Consistency of quality attributes for the glycosylated monoclonal antibody Humira® (adalimumab).

ABSTRACT: Humira® (adalimumab) is a recombinant human IgG1 monoclonal antibody (mAb) glycoprotein consisting of 1330 amino acids that is specific for human tumor necrosis factor (TNF). The biological activity and clinical profile of mAb therapeutics, including adalimumab, is influenced by their protein structure and glycosylation patterns, which can be affected by the expression system, cell culture conditions and purification process methodology. While clinical outcome cannot yet be attributed to many of the individual structural features that constitute a mAb, it is evident that detailed structural attribute analysis is necessary if structural contributions to function are to be comprehensively defined. Adalimumab product quality data generated from over a decade of manufacturing across multiple production sites and through a series of manufacturing scale changes are presented here. These data reveal a consistent and tightly controlled profile for the product.

SUBMITTER: Tebbey PW

PROVIDER: S-EPMC4622832 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Consistency of quality attributes for the glycosylated monoclonal antibody Humira® (adalimumab).

Tebbey Paul W PW Varga Amy A Naill Michael M Clewell Jerry J Venema Jaap J

mAbs 20150101 5

Humira® (adalimumab) is a recombinant human IgG1 monoclonal antibody (mAb) glycoprotein consisting of 1330 amino acids that is specific for human tumor necrosis factor (TNF). The biological activity and clinical profile of mAb therapeutics, including adalimumab, is influenced by their protein structure and glycosylation patterns, which can be affected by the expression system, cell culture conditions and purification process methodology. While clinical outcome cannot yet be attributed to many of ...[more]

PMID: 26230301

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Project description:Collagen hydrolysates are dietary supplements used for nutritional and medical purposes. They are complex mixtures of low-molecular-weight peptides obtained from the enzymatic hydrolysis of collagen, which provide intrinsic batch-to-batch heterogeneity. In consequence, the quality of these products, which is related to the reproducibility of their mass distribution pattern, should be addressed. Here, we propose an analytical approach to determine the peptide pattern as a quality attribute of Colagenart®, a product containing collagen hydrolysate. In addition, we evaluated the safety by measuring the viability of two cell lines exposed to the product. The consistency of peptide distribution was determined using Size Exclusion Chromatography (SEC), Mass Spectrometry coupled to a reversed phase UPLC system (MS-RP-UPLC), and Shaped-pulse off-resonance water-presaturation proton nuclear magnetic resonance spectrometry [1 Hwater_presat NMR]. The mass distribution pattern determined by SEC was in a range from 1.35 to 17 kDa, and from 2 to 14 kDa by MS-RP-UPLC. [1 Hwater_presat NMR] showed the detailed spin-systems of the collagen hydrolysates components by global assignment of backbone Hα and NH, as well as side-chain proton resonances. Additionally, short-range intraresidue connectivity pathways of identified spin-regions were obtained by a 2D homonuclear shift correlation Shaped-pulse solvent suppression COSY scheme. Safety analysis of Colagenart® was evaluated in CaCo-2 and HepG2 cells at 2.5 and 25 μg/mL and no negative effects were observed. The results demonstrated batch-to-batch reproducibility, which evinces the utility of this approach to establish the consistency of the quality attributes of collagen hydrolysates. PRACTICAL APPLICATION: We propose state-of-the art analytical methodologies (SEC, MS, and NMR) to evaluate peptide profile and composition of collagen hydrolysates as quality attributes. These methodologies are suitable to be implemented for quality control purposes.

Dataset Information

Consistency of quality attributes for the glycosylated monoclonal antibody Humira® (adalimumab).

Publications

Consistency of quality attributes for the glycosylated monoclonal antibody Humira® (adalimumab).

Similar Datasets

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