Small-scale screening method for low-viscosity antibody solutions using small-angle X-ray scattering

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• 作者：Masakazu Fukuda^a ; ^{fukuda.masakazu76@chugai-pharm.co.jp} ; Atsushi Watanabe^a ; Akira Hayasaka^c ; Masaru Muraoka^d ; Yuji Hori^c ; Tadao Yamazaki^a ; Yoshimi Imaeda^b ; Akiko Koga^a
• 关键词：Dmaxapp ; apparent maximum dimension ; Rgapp ; apparent radius of gyration ; EMS ; electromagnetically spinning ; IFT ; indirect Fourier transformation ; p(r) ; pair&ndash ; distance distribution function ; q.s. ; quantity sufficient ; SAXS ; small-angle X-ray scattering
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：112
• 期：Complete
• 页码：132-137
• 全文大小：790 K
• 卷排序：112

文摘

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 1–80 mg/mL. With higher-viscosity mAb1, on the other hand, self-association was detected in the range of 10–20 mg/mL and was clearly enhanced by a decrease in temperature. The viscosities of mAb solutions at 160, 180, and 200 mg/mL at 25 °C quantitatively correlated very well with the particle size parameters obtained by SAXS measurements of mAb solutions at 15 mg/mL at 5 °C. The quantity of mAb sample required for the SAXS measurements was only 0.15 mg, 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.