UNIGE document Scientific Article
previous document  unige:133134  next document
add to browser collection

Determination of size variants by CE-SDS for approved therapeutic antibodies: Key implications of subclasses and light chain specificities

Wagner, Elsa
Colas, Olivier
Chenu, Stéphane
Cianferani, Sarah
François, Yannis
show hidden authors show all authors [1 - 11]
Published in Journal of pharmaceutical & biomedical analysis. 2020, vol. 184, 113166
Abstract In the present work, a generic non-reducing capillary electrophoresis sodium dodecyl sulphate (nrCE-SDS) method was tested for a wide range of 26 FDA and EMA approved monoclonal antibodies (mAbs) and 2 antibody drug conjugates (ADCs) as well as for the NISTmab, in a QC environment (e.g. testing quality requirements for batch manufacturing or batch release). This method allows obtaining rapidly and accurately the amount of size variants in drug products within about 40 min and may be used for batch release and consistency as well as for stability and shelf-life. First, the method repeatability was found to be excellent in terms of relative migration times and relative proportions of fragments (average RSD values of 0.3 and 0.2 %, on relative migration times and relative percentages of fragments, respectively), thanks to the addition of an internal standard. A panel of chimeric, humanized and human mAbs were tested, belonging to different subclasses (heavy chain gamma 1, 2, 2/4 and 4) and light chain types (κ or λ) and produced in different cell lines (CHO, NS0 and SP2/0). For all these biopharmaceutical products, the amount of H2L2 species was comprised between 90.9 % and 97.7 %, except for the two mAbs belonging to the IgG1λ subclass, namely avelumab and belimumab, which were prone to partial reduction during the sample preparation at 70 °C. Based on the CE-SDS results obtained for a diverse panel of therapeutic antibodies investigated in this study, and covering a wide range of structural and physico-chemical properties, a specification on the intact antibody content (H2L2) greater than 90 % can be achieved.
Keywords CE-SDSQuality controlSize variantsPharmacopeia methodLow molecular weight species
PMID: 32113118
Full text
Research group Sciences analytiques
(ISO format)
WAGNER, Elsa et al. Determination of size variants by CE-SDS for approved therapeutic antibodies: Key implications of subclasses and light chain specificities. In: Journal of Pharmaceutical and Biomedical Analysis, 2020, vol. 184, p. 113166. doi: 10.1016/j.jpba.2020.113166 https://archive-ouverte.unige.ch/unige:133134

168 hits

1 download


Deposited on : 2020-03-26

Export document
Format :
Citation style :