title: Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.
abstract: Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.
authors.affiliation: a Biotherapeutics Pharmaceutical Sciences Research and Development, Pfizer Inc. , 700 Chesterfield Parkway West, Chesterfield , Missouri , 63017 , USA.
authors.forename: Dheeraj S
authors.initials: DS
authors.lastname: Tomar
authors.affiliation: a Biotherapeutics Pharmaceutical Sciences Research and Development, Pfizer Inc. , 700 Chesterfield Parkway West, Chesterfield , Missouri , 63017 , USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: a Biotherapeutics Pharmaceutical Sciences Research and Development, Pfizer Inc. , 700 Chesterfield Parkway West, Chesterfield , Missouri , 63017 , USA.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: a Biotherapeutics Pharmaceutical Sciences Research and Development, Pfizer Inc. , 700 Chesterfield Parkway West, Chesterfield , Missouri , 63017 , USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Goswami
authors.affiliation: b Biotherapeutics Pharmaceutical Sciences Research and Development, Pfizer Inc ., 1 Burtt Road, Andover , Massachusetts , 01810 , USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D014783:Viscosity
chemical_list: D000911:Antibodies, Monoclonal
keywords: Electrostatics; high concentration; hydrophobicity; intermolecular interactions; monoclonal antibody solution; networks; viscosity