Theoretical approximations and experimental extinction coefficients of biopharmaceuticals

Miranda-Hernández, Mariana P.; Valle-González, Elba R.; Ferreira-Gómez, David; Pérez, Nestor O.; Flores-Ortiz, Luis F.; Medina‐Rivero, Emilio

doi:10.1007/s00216-015-9261-6

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…All experiments were modified from the standard synthesis conditions (STD) used for GA manufacturing. GA produced by STD (GA-STD, Probioglat) has been extensively characterized in terms of its distinctive and equivalent molecular mass 45 ; electric charge and hydrophobicity 46 ; and refractive index increment and extinction coefficient 51 with respect to the reference medicinal product (Copaxone).…”

Section: Resultsmentioning

confidence: 99%

Process signatures in glatiramer acetate synthesis: structural and functional relationships

Campos-García¹,

Herrera-Fernández²,

Garza³

et al. 2017

Sci Rep

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Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

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Section: Resultsmentioning

confidence: 99%

Process signatures in glatiramer acetate synthesis: structural and functional relationships

Campos-García¹,

Herrera-Fernández²,

Garza³

et al. 2017

Sci Rep

Self Cite

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“…Stock solutions of IFX (CT-P13 or Remicade, as indicated) were prepared in water at 10 mg/mL. The concentration was checked by measuring the absorbance at 280 nm using an extinction coefficient of 217440 M −1 cm −1 45 . The stock solutions were diluted in water to prepare the working solutions and then used for calibration curves and quality controls (QC).…”

Section: Methodsmentioning

confidence: 99%

A Surface Plasmon Resonance-based assay to measure serum concentrations of therapeutic antibodies and anti-drug antibodies

Beeg

Nobili

Orsini

et al. 2019

Sci Rep

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Therapeutic drug and immunogenicity monitoring (TDIM) is increasingly proposed to guide therapy with biologics, characterised by high inter-individual variability of their blood levels, to permit objective decisions for the management of non-responders and reduce unnecessary interventions with these expensive treatments. However, TDIM has not yet entered clinical practice partly because of uncertainties regarding the accuracy and precision of enzyme-linked immunosorbent assays (ELISA). Here we report the characterisation of a novel surface plasmon resonance (SPR)-based TDIM, applied to the measurement of serum concentrations of infliximab, an antibody against tumour necrosis factor α (anti-TNFα), and anti-infliximab antibodies. SPR has the obvious advantages of directly detecting and measuring serum antibodies in minutes, avoiding the long incubation/separation/washing/detection steps of the methods proposed so far, reducing complexity and variability. Moreover, drug and anti-drug antibodies can be measured simultaneously. This new method was validated for sensitivity and reproducibility, and showed cost-effectiveness over commercial ELISA kits. This method may be applied to other biotherapeutics. These data pave the way for the development of SPR-based point-of-care devices for rapid on-site analysis.

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“…Because the absorbance of the protein solution can be measured using a low cost instrument with high reproducibility and simple measurement principle based on the Lambert-beer’s law, the absorbance at 280 nm is frequently used to determine antibody concentration ( Miranda-Hernandez et al, 2016 ; Cole et al, 2018 ). Antibody concentration is essential in the quality control of an antibody drug, and the accurate determination of the extinction coefficient at 280 nm of the RM can lead to various application of the RM with high accuracy.…”

Section: Resultsmentioning

confidence: 99%

Characterization and Value Assignment of a Monoclonal Antibody Reference Material, NMIJ RM 6208a, AIST-MAB

Kinumi

Saikusa²,

Kato³

et al. 2022

Front. Mol. Biosci.

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Monoclonal antibodies have been established as the largest product class of biopharmaceuticals. Since extensive characterization is required for development and quality control of monoclonal antibody, a widely available reference material (RM) is needed. Herein, a humanized IgG1κ monoclonal antibody reference material, RM 6208-a, AIST-MAB, was established by the National Metrology Institute of Japan, National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). The monoclonal antibody solution was produced as a pharmaceutical grade using a Chinese hamster ovary-derived cell line. The assigned indicative value represents the concentration of the antibody with a heterotetrameric structure including oligomeric forms, determined by an amino acid analysis using isotope dilution mass spectrometry, and their homogeneity and stability were assessed. In addition to antibody concentration, various physicochemical properties, including peptide mapping data, charge variants, and aggregates, were examined. This RM is intended for use in validation of analytical procedures and instruments such as a system suitability test for quantification of antibody. It is also intended for comparing and evaluating the results of antibody analyses across analytical methods and analytical laboratories such as inter-laboratory comparison. Both the material and the set of data from our study provide a tool for an accurate and reliable characterization of product quality attributes of monoclonal antibodies in biopharmaceutical and metrology communities.

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Theoretical approximations and experimental extinction coefficients of biopharmaceuticals

Cited by 11 publications

References 24 publications

Process signatures in glatiramer acetate synthesis: structural and functional relationships

Process signatures in glatiramer acetate synthesis: structural and functional relationships

A Surface Plasmon Resonance-based assay to measure serum concentrations of therapeutic antibodies and anti-drug antibodies

Characterization and Value Assignment of a Monoclonal Antibody Reference Material, NMIJ RM 6208a, AIST-MAB

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