An Exploration of the Role of Electrostatic Interactions on Monoclonal Antibody Behavior

Open Access
- Author:
- Butts, Thomas
- Area of Honors:
- Chemical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Andrew Zydney, Thesis Supervisor
Ali Borhan, Thesis Honors Advisor - Keywords:
- Chemical Engineering
Virus
Filtration
Pharmaceutical
biotech
purification
mAb
Monoclonal Antibody - Abstract:
- Monoclonal antibodies treatments are an ever-growing sector within the pharmaceutical industry. These biologics offer a novel, effective, and safe way of treating a variety of conditions and diseases. With the increasing demand for these treatments and the high concentration doses that are required for therapeutic use, it is imperative to make improvements upon the manufacturing of these proteins. Virus removal filtration is currently one of the most robust methods of protein purification. However, many monoclonal antibodies experience aggregation which results in filter clogging and decreased protein throughput. Investigating the behavior of monoclonal antibodies and their fouling phenomena are essential to optimizing filtration processes. The objectives of this project are to evaluate the behavior of a model antibody and to develop an analytical lens by which to analyze other antibodies. This project investigates the electrostatic interactions between monoclonal antibodies and added ionic compounds or charged excipients. The effects of adding Na2SO4, CaCl2, NaCl, and L-Arginine to a model monoclonal antibody were studied throughout this experiment. Thereafter, a Hofmeister series and Debye length analytical lens is developed to evaluate other antibodies and their fouling properties. The results of these experiments indicate that a reverse Hofmeister series is a useful tool to predict aggregation behavior for proteins that have a pI greater than the solution pH. This reverse Hofmeister series may provide a method of choosing which salts to add to monoclonal antibody solutions to improve stability and reduce aggregation. Further experimentation must be conducted to determine if Debye length corresponds to aggregation behavior.