Automation of mAbs stress testing with visual inspection on Junior

Significance of the Topic

Manual visual inspection of biologic formulations is inherently qualitative, subjective, and prone to human error. Traditional turbidity and particle-counting assays often consume sample volume, require multiple replicates, and do not retain visual records. The Visual Inspection Station (VIS), integrated into automated platforms such as the Junior system, addresses these challenges by non-destructively quantifying color, visible particle counts, and turbidity in sealed vials. This automation reduces hands-on time, improves reproducibility, preserves precious samples, and archives images for later verification.

Objectives and Study Overview

This application note evaluates the performance of the VIS module on a Junior platform for stress testing monoclonal antibody (mAb) formulations. Key goals include:

• Automating color matching against standardized calibration references.
• Quantifying visible particulate counts under motion-induced suspension profiles.
• Measuring turbidity across a calibrated range without opening vials.
• Demonstrating the impact of formulation variables (concentration and surfactant addition) on stability metrics.

Methodology and Instrumentation

• Sample Preparation: mAb A was prepared at concentrations from 1 to 150 mg/mL in 10 mM histidine, pH 6.0, with and without 0.1% polysorbate 80 (PS80). mAb B in a proprietary formulation served as a stable control.
• Color Calibration: European Pharmacopoeia Color Reference Solutions BY1–BY6 and a blank water standard.
• Turbidity Calibration: AMCO Clear standards spanning 0–800 NTU.
• Instrumentation: VIS module mounted on the Junior automated platform (also compatible with Big Kahuna). VIS employs a camera and lighting at 180° for turbidity and a motion-based imaging sequence for particle detection.
• Software: LEA Library Studio for experimental design, Automation Studio for execution, and the LEA Analysis Add-in for Excel for data processing.

Main Results and Discussion

• Color Analysis: mAb A samples matched calibration standards with relevance scores of 99.7–100% and low Euclidean match distances, accurately tracking yellowing from the blank at 1 mg/mL up to BY4 at 150 mg/mL.
• Visible Particle Count: Particle counts decreased from 32±5.3 at 1 mg/mL to 8±0.9 at 150 mg/mL, demonstrating an inverse correlation between protein concentration and detectable moving particles.
• Turbidity Measurement: mAb A exhibited progressive turbidity increases with extended vortex stress, exceeding 800 NTU after 180 minutes. Addition of 0.1% PS80 prevented turbidity rises, mirroring the stability observed for the mAb B control.

Benefits and Practical Applications

• Non-destructive testing preserves samples for downstream analyses or identification of individual particles.
• Automated workflows reduce hands-on time to minutes per set of replicates and eliminate subjective variability.
• Image archiving enables retrospective verification of color matches, particle events, and turbidity evaluations.
• High throughput and reproducibility support formulation screening, stability studies, and quality control operations.

Future Trends and Potential Applications

• Expansion to other biologic modalities, including vaccines, cell therapies, and protein conjugates.
• Integration with laboratory information management systems (LIMS) and digital QA/QC pipelines for fully traceable data.
• Application of machine learning and AI to enhance particle classification and detect sub-visible events.
• Miniaturized or in-line VIS modules for real-time monitoring during production and fill-finish operations.

Conclusion

The VIS technology on the Junior automated platform offers a robust, non-destructive solution for stress testing monoclonal antibody formulations. By combining quantitative color matching, motion-based particle detection, and linear turbidity measurement in sealed vials, VIS streamlines stability assessment, conserves sample volume, and provides comprehensive visual records. This capability supports accelerated formulation development, rigorous quality control, and efficient screening of biologic drug candidates.

References

No references were provided in the source text.