Paper Number
SC27 

Session
Suspensions, Colloids and Granular Systems

Title
Does the Huggins coefficient describe the thermodynamics & rheology of concentrated monoclonal antibody formulations?

Presentation Date and Time
October 11, 2017 (Wednesday) 1:30

Track / Room
Track 3 / Crystal C

Authors (Click on name to view author profile)

1. Pathak, Jai A. (NIAID NIH, Vaccine Production Program)
2. Nugent, Sean (NIAID NIH, Vaccine Production Program)
3. Bender, Michael (NIAID NIH, Vaccine Production Program)
4. Woldeyes, Mahlet (Univ. of Delaware, Dept. of Chemical & Biomolecular Engineering)
5. Corbett, Daniel (Univ. of Manchester, Chemical Engineering & Analytical Science)
6. Curtis, Robin (Univ. of Manchester, Chemical Engineering & Analytical Science)
7. Furst, Eric M. (Univ. of Delaware, Dept. of Chemical & Biomolecular Engineering)
8. Roberts, Christopher J. (Univ. of Delaware, Dept. of Chemical & Biomolecular Engineering)
9. Douglas, Jack F. (NIST, Materials Science & Engineering Division)

Author and Affiliation Lines (in printed abstract book)
Jai A. Pathak¹, Sean Nugent¹, Michael Bender¹, Mahlet Woldeyes², Daniel Corbett³, Robin Curtis³, Eric M. Furst², Christopher J. Roberts², and Jack F. Douglas^4
1Vaccine Production Program, NIAID NIH, Gaithersburg, MD 20878; ²Dept. of Chemical & Biomolecular Engineering, Univ. of Delaware, Newark, DE; ³Chemical Engineering & Analytical Science, Univ. of Manchester, Manchester, United Kingdom; ⁴Materials Science & Engineering Division, NIST, Gaithersburg, MD

Speaker / Presenter 
Pathak, Jai A.

Text of Abstract
Monoclonal Antibodies (mAbs) are prolifically used to vaccinate against various infectious diseases and as therapeutics for numerous clinical indications. Shear viscosity of mAb formulations is both a constituent engineering input for delivery device design, and a sensitive metric of protein aggregation at (supra-)molecular lengthscales, e.g. reversible self-association, and sub-visible particle formation. Therefore, mAb formulation development requires facile high-throughput measurement and prediction/ranking of formulation shear viscosity. We first show in this talk that the leading virial diffusion interaction parameter, k_D, is unsurprisingly a poor predictor of concentrated formulation viscosity, since it ignores hydrodynamic interactions in concentrated systems. In the quest for appropriate holistic descriptors of concentrated mAb solution rheology and thermodynamics, we test the seminal theory of Russel, who derived a prediction for the Huggins coefficient k_H of sticky spheres interacting with a short-range attraction and long-range repulsion in terms of the osmotic second virial coefficient, B₂₂ (normalized by its hard sphere value). While globular proteins and monoclonal antibodies can be readily mapped as sticky spheres due to the presence of charged surface patches, surprisingly this elegant theory of Russel has not been interrogated in these systems. We are currently measuring k_H and B₂₂ for various NIH Vaccine Research Center mAb molecules in different solution conditions. In this talk these data, and data on other molecules studied by this team, will be presented and their implications for Russel’s model will be critically examined, along with that of the predictions of Kholodenko and Douglas, who derived a Generalized Stokes-Einstein relation for concentrated suspensions and proposed the sum rule: k_D = B₂₂ – [η]; [η] denotes intrinsic viscosity.