Developing A High-Throughput Formulation Development Platform For High-Concentration, Therapeutic Monoclonal Antibodies

Some of the challenges in the early stages of a pharmaceutical are a limited supply of protein to use in formulation screening studies, and a need to obtain stability data quickly to initiate tox studies. One approach commonly used to conserve protein is to screen a large number of excipients at a lower concentration and then use the data generated to predict high-concentration trends.

However, trends observed at low protein concentration may not reflect the trends at a higher concentration where long-term stability is more likely to be a concern. This work demonstrates how a high-throughput, micro-well plate platform can be used to economically screen a model IgG1 mAb at 120 mg/ml in 96 formulations while minimizing protein consumed and generating large amount of data quickly. To evaluate the risk of using low-concentration data to predict stability trending at higher concentrations comparisons are made between the screening study executed at a high (120mg/mL) vs. low ( < 10 mg/mL) mAb concentration.