title: Small-scale screening method for low-viscosity antibody solutions using small-angle X-ray scattering.
abstract: In this study, we investigated the concentration range in which self-association starts to form in humanized IgG monoclonal antibody (mAb) solutions. Furthermore, on the basis of the results, we developed a practical method of screening for low-viscosity antibody solutions by using small-angle X-ray scattering (SAXS) measurements utilizing small quantities of samples. With lower-viscosity mAb3, self-association was not detected in the range of 1-80mg/mL. With higher-viscosity mAb1, on the other hand, self-association was detected in the range of 10-20mg/mL and was clearly enhanced by a decrease in temperature. The viscosities of mAb solutions at 160, 180, and 200mg/mL at 25°C quantitatively correlated very well with the particle size parameters obtained by SAXS measurements of mAb solutions at 15mg/mL at 5°C. The quantity of mAb sample required for the SAXS measurements was only 0.15mg, which is about one-hundredth of that required for actual viscosity measurements at a high concentration, and such quantities could be available even at an early stage of development. In conclusion, the SAXS analysis method proposed in this study is a valuable tool for the development of concentrated mAb therapeutics with high manufacturability and high usability for subcutaneous injection.
authors.affiliation: Production Engineering Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan. Electronic address: fukuda.masakazu76@chugai-pharm.co.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Production Engineering Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Biologics Discovery Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba City, Shizuoka Pref. 412-8513, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hayasaka
authors.affiliation: Chugai Pharmabody Research Pte. Ltd., 3 Biopolis Drive, #07 - 11 to 16, Synapse, 138623, Singapore.
authors.forename: Masaru
authors.initials: M
authors.lastname: Muraoka
authors.affiliation: Biologics Discovery Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba City, Shizuoka Pref. 412-8513, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Production Engineering Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: CMC Development Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Imaeda
authors.affiliation: Production Engineering Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Koga
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D053838:Scattering, Small Angle; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G
keywords: Cluster; High concentration; Monoclonal antibody; Self-association; Small-angle X-ray scattering; Viscosity