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Aggregation Stability of a Monoclonal Antibody During Downstream Processing

Arosio, Paolo ; Barolo, Giuliano ; Müller-Späth, Thomas ; Wu, Hua ; Morbidelli, Massimo

In: Pharmaceutical Research, 2011, vol. 28, no. 8, p. 1884-1894

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    Titre
    • Aggregation Stability of a Monoclonal Antibody During Downstream Processing
    Auteur
    • Arosio, Paolo. Department of Chemistry and Applied Biosciences Institute for Chemical and Bioengineering, ETH Zurich, 8093, Zurich, Switzerland
    • Barolo, Giuliano. Department of Chemistry and Applied Biosciences Institute for Chemical and Bioengineering, ETH Zurich, 8093, Zurich, Switzerland
    • Müller-Späth, Thomas. Department of Chemistry and Applied Biosciences Institute for Chemical and Bioengineering, ETH Zurich, 8093, Zurich, Switzerland
    • Wu, Hua. Department of Chemistry and Applied Biosciences Institute for Chemical and Bioengineering, ETH Zurich, 8093, Zurich, Switzerland
    • Morbidelli, Massimo. Department of Chemistry and Applied Biosciences Institute for Chemical and Bioengineering, ETH Zurich, 8093, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Pharmaceutical Research, 2011, vol. 28, no. 8, p. 1884-1894. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:319992
    Summary
    ABSTRACT: Purpose: To study the effect of several operative parameters, particularly pH and salt concentration, on the stability and aggregation kinetics of IgG solutions under the conditions typically encountered in downstream processing. Methods: The time evolution of the aggregates is analyzed by a combination of dynamic light scattering, size exclusion chromatography (SEC) and field flow fractionation (FFF). Secondary structure changes are monitored by circular dichroism. Results: For the given antibody, it is found that at pH lower than 4.0 addition of salt induces a reversible aggregation to oligomers accompanied by an increase in the content of the β-sheet structure. The aggregation rate increases monotonically with the salt concentration. Both the SEC and FFF techniques are successfully applied to obtain the oligomer distributions, and their results are consistent. The modified Lumry-Eyring kinetic model can well describe the time evolutions of the oligomers. Conclusions: For the given antibody, low pH and presence of salt induce conformational changes that are responsible for the reversible aggregation, but in the investigated conditions only small soluble oligomers are formed and oligomer sizes larger than trimer are negligible. For this reason, no accompanied macroscopic changes can be observed