Fast tracked mAbs formulation development with the automated Big Kahuna viscosity station

Significance of the Topic

The formulation of high-concentration biologics, such as monoclonal antibodies and proteins, poses significant challenges due to elevated viscosities that can hinder manufacturing, delivery and stability. Rapid, low-volume viscosity screening is essential to accelerate candidate selection, optimize excipient conditions and ensure robust drug product performance.

Objectives and Overview of the Study

This study evaluates the performance of an automated microcapillary viscosity station integrated into the Big Kahuna high-throughput formulation system. Key goals include demonstrating reproducibility across viscosity standards and temperatures, assessing formulation impacts on viscosity using model proteins and eye-drop analogs, and monitoring stability-induced viscosity changes in multiple mAb formulations.

Methodology and Instrumentation

A miniature capillary viscometer with an automated positive displacement tip on the Big Kahuna platform enables controlled sample injection (100 µL) and inline washing to prevent cross-contamination. Temperature control spans 4 °C to 40 °C, while variable flow rates allow shear-rate-dependent measurements for Newtonian and non-Newtonian fluids. The viscosity (μ) is calculated from pressure drop, capillary dimensions and flow rate. Integration with Lab Execution and Analysis software links viscosity outputs to formulation designs and offline analytics.

Main Results and Discussion

• Reproducibility: Two viscosity standards (∼1 cP and ∼100 cP) measured ten times at 4 °C and 40 °C yielded RSDs below 6%, demonstrating precise performance across the target range.
• Protein model studies: Bovine serum albumin in PBS with Tween 80 and Tween 80 + sucrose showed a clear concentration-dependent viscosity increase, highlighting the effect of excipients on viscosity.
• Newtonian vs. non-Newtonian fluids: Refresh Tears® exhibited constant viscosity over shear rates (Newtonian behavior), while Refresh Liquigel® displayed shear-thinning characteristics, with viscosity halving at higher shear.
• mAb stability screening: Twelve formulations at 50 mg/mL remained stable over 90 days at 4 °C, 25 °C and 40 °C. High-concentration (210 mg/mL) formulations showed significant viscosity increases at elevated temperatures, with some exceeding 100 cP, underscoring the need for rapid stability profiling.

Benefits and Practical Applications

• High throughput: <3 minutes per sample with only 100 µL required, enabling broad formulation space exploration.
• Automated cleaning and temperature control reduce labor and error.
• Capability to characterize both Newtonian and shear-thinning formulations across relevant shear rates.
• Seamless data integration with LEA software supports comprehensive formulation screening, linking viscosity data with other analytical metrics.

Future Trends and Opportunities

• Real-time viscosity monitoring and process analytical technology integration for inline manufacturing control.
• Expansion of measurement range and miniaturization to further reduce sample consumption.
• Application of machine learning to correlate formulation variables with viscosity outcomes and predict long-term stability.
• Adoption in continuous-flow bioprocessing and automated formulation optimization workflows.

Conclusion

The automated Big Kahuna viscosity station offers a robust solution for rapid, low-volume viscosity screening of biologic formulations. Its high throughput, precise measurements across temperature and shear conditions, and integration with data management software significantly accelerate formulation development and stability assessment. This platform enables formulation scientists to make informed decisions early in the development process, improving efficiency and reducing resource use.