A fully integrated Big Kahuna workflow to automate the entire biologics formulation development process

Importance of the topic

The development of stable biologics formulations is critical for ensuring safety, efficacy and shelf life of therapeutic proteins. High-throughput screening and stability assessment enable formulation scientists to rapidly identify optimal buffer and excipient combinations, minimize material usage and accelerate timelines in research and development.

Objectives and study overview

This study demonstrates a fully automated workflow for buffer and excipient screening, sample stressing and multi-modal analysis using an integrated robotic platform. Forty-eight bovine serum albumin (BSA) formulations spanning five buffer systems (pH 4.5–7.0) and four excipient combinations were prepared and subjected to initial (t0), agitation, heat and freeze-thaw stress conditions. Key goals were to compare automated performance with manual methods and to reveal formulation stability trends.

Methodology

An automated platform performed:

• Liquid handling and compounding of formulations in 2 mL serum vials
• Sample distribution into vials and 96-well plates
• Automated stress application: agitation, heating and freeze-thaw cycles
• High-throughput analytics at t0 and after stressing

Used instrumentation

• Big Kahuna automation platform with dual robotic workstations, cooled storage bay, HEPA enclosure and vortexer deck
• Lab Execution and Analysis (LEA) software for instrument control, data collection and management
• Unchained Labs enhanced visual inspection station for turbidity, color and visible particle counts
• Wyatt DynaPro II dynamic light scattering (DLS)
• Molecular Devices SpectraMax microplate UV/Vis reader (A280 nm)
• Agilent 1100 HPLC for size-exclusion (SEC) and reversed-phase (RP) analyses

Main results and discussion

At t0, formulations were clear (5–13 NTU) with low particle counts (0–4) and viscosities (~1 cP). Visible color remained below the brown-yellow 7 standard. After stress application:

• Heat stress induced the largest increases in turbidity (>100 NTU), visible particles and color changes in several formulations.
• Freeze-thaw and agitation caused moderate rises in turbidity and particle counts.
• DLS polydispersity increased notably for low-pH formulations (4.5–5.0), with some samples exceeding measurement limits after stressing.
• RP and SEC HPLC showed >85% main peak area in all conditions, indicating preserved protein purity and colloidal stability.

Benefits and practical applications

The automated workflow delivered consistent, reproducible sample handling and data capture, eliminating manual variability. Centralized data linkage through LEA streamlined result interpretation and reporting. Comparing manual versus automated execution for 48 formulations revealed a 4–6 fold reduction in scientist hands-on time (6.1 h vs. 29.7 h). This efficiency gain supports larger screening matrices and faster decision making in formulation R&D.

Future trends and potential applications

Integration of advanced analytical methods such as high-throughput mass spectrometry or multi-angle light scattering could further expand data richness. Cloud-based data analytics and AI-driven formulation prediction tools hold promise for predictive stability modeling. Fully closed-loop automation, including automated decision-making and adaptive experimental design, will accelerate next-generation biologics formulation development.

Conclusion

This case study validates a fully automated, end-to-end biologics formulation workflow that combines compounding, stressing and multi-technique analysis on a single platform. The approach significantly reduces labor, enhances data integrity and accelerates formulation optimization, enabling formulation scientists to focus on strategic development tasks.