Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements. / Neergaard, Martin S; Kalonia, Devendra S; Parshad, Henrik; Nielsen, Anders; Møller, Eva H; van de Weert, Marco; Nielsen, Anders D.

In: European Journal of Pharmaceutical Sciences, Vol. 49, No. 3, 26.04.2013, p. 400-410.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Neergaard, MS, Kalonia, DS, Parshad, H, Nielsen, A, Møller, EH, van de Weert, M & Nielsen, AD 2013, 'Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements', European Journal of Pharmaceutical Sciences, vol. 49, no. 3, pp. 400-410. https://doi.org/10.1016/j.ejps.2013.04.019

APA

Neergaard, M. S., Kalonia, D. S., Parshad, H., Nielsen, A., Møller, E. H., van de Weert, M., & Nielsen, A. D. (2013). Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements. European Journal of Pharmaceutical Sciences, 49(3), 400-410. https://doi.org/10.1016/j.ejps.2013.04.019

Vancouver

Neergaard MS, Kalonia DS, Parshad H, Nielsen A, Møller EH, van de Weert M et al. Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements. European Journal of Pharmaceutical Sciences. 2013 Apr 26;49(3):400-410. https://doi.org/10.1016/j.ejps.2013.04.019

Author

Neergaard, Martin S ; Kalonia, Devendra S ; Parshad, Henrik ; Nielsen, Anders ; Møller, Eva H ; van de Weert, Marco ; Nielsen, Anders D. / Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements. In: European Journal of Pharmaceutical Sciences. 2013 ; Vol. 49, No. 3. pp. 400-410.

Bibtex

@article{f75cc65d061744268cdecb575a252b94,
title = "Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements",
abstract = "The purpose of this work was to explore the relation between protein-protein interactions (PPIs) and solution viscosity at high protein concentration using three monoclonal antibodies (mAbs), two of the IgG4 subclass and one of the IgG1 subclass. A range of methods was used to quantify the PPI either at low concentration (interaction parameter (kD) obtained from dynamic light scattering, DLS) or at high concentration (solution storage modulus (G') from ultrasonic shear rheology). We also developed a novel method for the determination of PPI using the apparent radius of the protein at either low or high protein concentration determined using DLS. The PPI measurements were correlated with solution viscosity (measured by DLS using polystyrene nanospheres and ultrasonic shear rheology) as a function of pH (4-9) and ionic strength (10, 50 and 150mM). Our measurements showed that the highest solution viscosity was observed under conditions with the most negative kD, the highest apparent radius and the lowest net charge. An increase in ionic strength resulted in a change in the nature of the PPI at low pH from repulsive to attractive. In the neutral to alkaline pH region the mAbs behaved differently with respect to increase in ionic strength. Two mAbs (A and B) showed little or no effect of increasing ionic strength, whereas mAb-C showed a remarkable decrease in attractive PPI and viscosity. Previous studies have mainly investigated mAbs of the IgG1 and IgG2 subclass. We show here, for the first time, that mAbs of the IgG4 subclass behave similar as the other subclasses. By comparison of the three tested mAbs with mAbs investigated in other studies a clear linear trend emerges between the pH of strongest attractive PPI and highest solution viscosity. The determination of PPI using either kD or apparent radius is thus a useful prediction tool in the determination of solution conditions that favors low solution viscosity at high protein concentration of therapeutically used mAb molecules. The novel methodology using apparent radius is a simple and rapid alternative to determine relative PPI directly under formulation conditions. The method can potentially serve as a high-throughput screening tool in formulation development.",
author = "Neergaard, {Martin S} and Kalonia, {Devendra S} and Henrik Parshad and Anders Nielsen and M{\o}ller, {Eva H} and {van de Weert}, Marco and Nielsen, {Anders D.}",
note = "Copyright {\circledC} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = "4",
day = "26",
doi = "10.1016/j.ejps.2013.04.019",
language = "English",
volume = "49",
pages = "400--410",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements

AU - Neergaard, Martin S

AU - Kalonia, Devendra S

AU - Parshad, Henrik

AU - Nielsen, Anders

AU - Møller, Eva H

AU - van de Weert, Marco

AU - Nielsen, Anders D.

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/4/26

Y1 - 2013/4/26

N2 - The purpose of this work was to explore the relation between protein-protein interactions (PPIs) and solution viscosity at high protein concentration using three monoclonal antibodies (mAbs), two of the IgG4 subclass and one of the IgG1 subclass. A range of methods was used to quantify the PPI either at low concentration (interaction parameter (kD) obtained from dynamic light scattering, DLS) or at high concentration (solution storage modulus (G') from ultrasonic shear rheology). We also developed a novel method for the determination of PPI using the apparent radius of the protein at either low or high protein concentration determined using DLS. The PPI measurements were correlated with solution viscosity (measured by DLS using polystyrene nanospheres and ultrasonic shear rheology) as a function of pH (4-9) and ionic strength (10, 50 and 150mM). Our measurements showed that the highest solution viscosity was observed under conditions with the most negative kD, the highest apparent radius and the lowest net charge. An increase in ionic strength resulted in a change in the nature of the PPI at low pH from repulsive to attractive. In the neutral to alkaline pH region the mAbs behaved differently with respect to increase in ionic strength. Two mAbs (A and B) showed little or no effect of increasing ionic strength, whereas mAb-C showed a remarkable decrease in attractive PPI and viscosity. Previous studies have mainly investigated mAbs of the IgG1 and IgG2 subclass. We show here, for the first time, that mAbs of the IgG4 subclass behave similar as the other subclasses. By comparison of the three tested mAbs with mAbs investigated in other studies a clear linear trend emerges between the pH of strongest attractive PPI and highest solution viscosity. The determination of PPI using either kD or apparent radius is thus a useful prediction tool in the determination of solution conditions that favors low solution viscosity at high protein concentration of therapeutically used mAb molecules. The novel methodology using apparent radius is a simple and rapid alternative to determine relative PPI directly under formulation conditions. The method can potentially serve as a high-throughput screening tool in formulation development.

AB - The purpose of this work was to explore the relation between protein-protein interactions (PPIs) and solution viscosity at high protein concentration using three monoclonal antibodies (mAbs), two of the IgG4 subclass and one of the IgG1 subclass. A range of methods was used to quantify the PPI either at low concentration (interaction parameter (kD) obtained from dynamic light scattering, DLS) or at high concentration (solution storage modulus (G') from ultrasonic shear rheology). We also developed a novel method for the determination of PPI using the apparent radius of the protein at either low or high protein concentration determined using DLS. The PPI measurements were correlated with solution viscosity (measured by DLS using polystyrene nanospheres and ultrasonic shear rheology) as a function of pH (4-9) and ionic strength (10, 50 and 150mM). Our measurements showed that the highest solution viscosity was observed under conditions with the most negative kD, the highest apparent radius and the lowest net charge. An increase in ionic strength resulted in a change in the nature of the PPI at low pH from repulsive to attractive. In the neutral to alkaline pH region the mAbs behaved differently with respect to increase in ionic strength. Two mAbs (A and B) showed little or no effect of increasing ionic strength, whereas mAb-C showed a remarkable decrease in attractive PPI and viscosity. Previous studies have mainly investigated mAbs of the IgG1 and IgG2 subclass. We show here, for the first time, that mAbs of the IgG4 subclass behave similar as the other subclasses. By comparison of the three tested mAbs with mAbs investigated in other studies a clear linear trend emerges between the pH of strongest attractive PPI and highest solution viscosity. The determination of PPI using either kD or apparent radius is thus a useful prediction tool in the determination of solution conditions that favors low solution viscosity at high protein concentration of therapeutically used mAb molecules. The novel methodology using apparent radius is a simple and rapid alternative to determine relative PPI directly under formulation conditions. The method can potentially serve as a high-throughput screening tool in formulation development.

U2 - 10.1016/j.ejps.2013.04.019

DO - 10.1016/j.ejps.2013.04.019

M3 - Journal article

C2 - 23624326

VL - 49

SP - 400

EP - 410

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

IS - 3

ER -

ID: 45760574