A Systematic Multitechnique Approach for Detection and Characterization of Reversible Self-Association during Formulation Development of Therapeutic Antibodies

被引:28
作者
Esfandiary, Reza [1 ]
Hayes, David B. [2 ]
Parupudi, Arun [2 ]
Casas-Finet, Jose [2 ]
Bai, Shufeng [1 ]
Samra, Hardeep S. [1 ]
Shah, Ambarish U. [1 ]
Sathish, Hasige A. [1 ]
机构
[1] Medimmune Inc, Dept Formulat Sci, Gaithersburg, MD 20878 USA
[2] Medimmune Inc, Dept Analyt Biochem, Gaithersburg, MD 20878 USA
关键词
monoclonal antibody; reversible self-association; intermolecular interaction; formulation; screening; light scattering (dynamic); light scattering (static); analytical ultracentrifugation; high-throughput technologies; biotechnology; BOVINE SERUM-ALBUMIN; STATIC LIGHT-SCATTERING; 2ND VIRIAL-COEFFICIENT; HARD PARTICLE MODEL; MONOCLONAL-ANTIBODY; PROTEIN AGGREGATION; IONIC-STRENGTH; VISCOSITY; DIMER; IGG1;
D O I
10.1002/jps.23654
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In addition to controlling typical instabilities such as physical and chemical degradations, understanding monoclonal antibodies' (mAbs) solution behavior is a key step in designing and developing process and formulation controls during their development. Reversible self-association (RSA), a unique solution property in which native, reversible oligomeric species are formed as a result of the noncovalent intermolecular interactions has been recognized as a developability risk with the potential to negatively impact manufacturing, storage stability, and delivery of mAbs. Therefore, its identification, characterization, and mitigation are key requirements during formulation development. Considering the large number of available analytical methods, choice of the employed technique is an important contributing factor for successful investigation of RSA. Herein, a multitechnique (dynamic light scattering, multiangle static light scattering, and analytical ultracentrifugation) approach is employed to comprehensively characterize the self-association of a model immunoglobulin G1 molecule. Studies herein discuss an effective approach for detection and characterization of RSA during biopharmaceutical development based on the capabilities of each technique, their complementarity, and more importantly their suitability for the stage of development in which RSA is investigated. (C) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3089-3099, 2013 This article from this special issue was previously published in the Journal of Pharmaceutical Sciences, Volume 102, Issue 1:62-72, 2013. The full text of this article can also be read in issue 102#1 on Wiley Online Library - JPS23369
引用
收藏
页码:3089 / 3099
页数:11
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