No Touching! Abrasion of Adsorbed Protein Is the Root Cause of Subvisible Particle Formation During Stirring

Ahmad S. Sediq; R. B. van Duijvenvoorde; Wim Jiskoot; M. Reza Nejadnik

doi:10.1016/j.xphs.2015.10.003

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No Touching! Abrasion of Adsorbed Protein Is the Root Cause of Subvisible Particle Formation During Stirring

Journal article

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Peer reviewed

No Touching! Abrasion of Adsorbed Protein Is the Root Cause of Subvisible Particle Formation During Stirring

Ahmad S. Sediq, R. B. van Duijvenvoorde, Wim Jiskoot and M. Reza Nejadnik

Journal of pharmaceutical sciences, Vol.105(2), pp.519-529

02/01/2016

DOI: 10.1016/j.xphs.2015.10.003

PMID: 26869415

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https://doi.org/10.1016/j.xphs.2015.10.003View

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Abstract

This study addressed the effect of contact sliding during stirring of a monoclonal antibody solution on protein aggregation, in particular, in the nanometer and micrometer size range. An overhead stirring setup was designed in which the presence and magnitude of the contact between the stir bar and the container could be manipulated. A solution of 0.1 mg/mL of a monoclonal antibody (IgG) in phosphate buffered saline was stirred at 300 rpm at room temperature. At different time points, samples were taken and analyzed by nanoparticle tracking analysis, flow imaging microscopy, and size-exclusion chromatography. In contrast to nonecontact-stirred and unstirred samples, the contact-stirred sample contained several-fold more particles and showed a significant loss of monomer. No increase in oligomer content was detected. The number of particles formed was proportional to the contact area and the magnitude of the normal pressure between the stir bar and the glass container. Extrinsic 9-(2,2-dicyanovinyl) julolidine fluorescence indicated a conformational change for contact-stirred protein samples. Presence of polysorbate 20 inhibited the formation of micron-sized aggregates. We suggest a model in which abrasion of the potentially destabilized, adsorbed protein leads to aggregation and renewal of the surface for adsorption of a fresh protein layer. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Chemistry

Chemistry, Medicinal

Chemistry, Multidisciplinary

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Physical Sciences

Science & Technology

Details

Title: Subtitle: No Touching! Abrasion of Adsorbed Protein Is the Root Cause of Subvisible Particle Formation During Stirring
Creators: Ahmad S. Sediq - Centre for Human Drug Research
R. B. van Duijvenvoorde - Centre for Human Drug Research
Wim Jiskoot - Leiden University
M. Reza Nejadnik - Centre for Human Drug Research
Resource Type: Journal article
Publication Details: Journal of pharmaceutical sciences, Vol.105(2), pp.519-529
DOI: 10.1016/j.xphs.2015.10.003
PMID: 26869415
NLM abbreviation: J Pharm Sci
ISSN: 0022-3549
eISSN: 1520-6017
Publisher: Wiley
Number of pages: 11
Grant note: 12144 / Dutch Technology Foundation STW of the Netherlands Organization for Scientific Research [NWO] Ministry of Economic Affairs 115363 / Innovative Medicines Initiative Joint Undertaking - European Union
Language: English
Date published: 02/01/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984420843002771

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