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

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 mAbl, 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 degrees C quantitatively correlated very well with the particle size parameters obtained by SAXS measurements of mAb solutions at 15 mg/mL at 5 degrees 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. (C) 2016 Elsevier B.V. All rights reserved.