Accelerating High Concentration Formulation Development with Big Data-Driven High-Throughput Technologies

High-concentration biologics, particularly monoclonal antibodies (mAbs), offer significant advantages, including cost savings and the ability to enable subcutaneous administration, which enhances patient compliance. However, developing these formulations presents notable challenges, such as maintaining protein stability, minimizing viscosity, and optimizing manufacturability. To meet the growing demand for efficient development in this area, a high-throughput (HT) platform has been established, offering a powerful solution to overcome the complex issues associated with high-concentration protein formulations.

This session introduces a cutting-edge HT platform that integrates automated instrumentation, big data analytics, and novel viscosity reducers with unique excipient combinations. These elements work in tandem to enhance formulation stability while minimizing viscosity, ultimately leading to faster and more effective development of high-concentration formulations. The platform addresses the delicate balance required for protein conformational, colloidal and chemical stabilities, and solution viscosity—factors that are crucial for creating stable, manufacturable, and deliverable high-concentration biologics.

Traditional sequential formulation development approaches are time-consuming, material-intensive, and often fail to uncover critical interactions between formulation parameters, such as pH, buffer systems, and excipients. In contrast, HT screening enables simultaneous investigation of multiple parameters across a matrix of formulations, dramatically reducing the time, resources, and costs involved in formulation development. This platform allows scientists to condense development timelines from 14–18 weeks with conventional methods to as little as 7 weeks using HT screening.
Key features of the platform include 384-well-based biophysical screening, a streamlined HT viscosity screening approach, and advanced statistical analyses to identify optimal formulation candidates. The session will present a case study using mAb-A (IgG1κ) that demonstrates the platform's effectiveness. The HT screening process successfully identified formulation candidates that outperformed the commercial formulation in a formulation confirmation study, exhibiting superior stability and more favorable viscosity profiles at the same protein concentration.

Beyond these immediate successes, the HT platform also uncovered unique interactions between excipients, such as arginine-aspartate and mAb-A, offering valuable insights for future formulation development. These discoveries emphasize the importance of employing HT screening to explore a broader range of excipient-protein interactions that would otherwise go unnoticed with traditional approaches.

One of the key takeaways from the case study is the critical role of multiple orthogonal assays in accurately measuring protein stability indicators. For instance, the session will highlight how the correlations between Differential Scanning Fluorimetry (DSF) and Isothermal Chemical Denaturation (ICD) assays, as well as between the diffusion interaction parameter (kD) and the second virial coefficient (A2), are dependent on the pH and ionic strength of the solution. This finding underscores the necessity of using a combination of assays to obtain a comprehensive understanding of protein stability.

Attendees will gain a deeper understanding of how HT technologies, paired with big data and novel excipient strategies, are transforming high-concentration protein formulation development. This session is essential for biopharmaceutical scientists, bioprocess engineers, R&D leaders, and data scientists interested in accelerating formulation timelines while ensuring product quality and stability.