Method transfer onto the Thermo Scientific Vanquish HPLC/UHPLC platform: A CDMO perspective

Importance of the Topic

Liquid chromatography method transfer is vital for ensuring analytical consistency and compliance across pharmaceutical contract development and manufacturing organizations (CDMOs). Modernizing aging HPLC instruments enhances data quality, compliance with cGMP regulations, and operational efficiency.

Objectives and Study Overview

The study examines the transfer of existing HPLC methods onto the Thermo Scientific Vanquish UHPLC platform within a large CDMO network. It aims to outline best practices for method adaptation, regulatory compliance, and performance comparison with legacy systems.

Methodology and Instrumentation

Gradient delay volume (GDV) adjustment is central to preserving chromatographic profiles during method transfer. Experimental GDV measurements use step gradients with model compounds and calculation of T50 response times. Hardware modifications, such as replacing static mixers and sample loops, enable tuning of GDV without requalifying instruments.
Instrumental setup includes:

• Thermo Scientific Vanquish Flex UHPLC with quaternary pump and biocompatible flow path
• Vanquish Core and Horizon systems for alternative workflows
• Adjustable sample loops (10 to 250 μL) and static mixers (150 to 1500 μL)
• Compatibility with Waters Empower 3 CDS for data integration

Main Results and Discussion

Method transfer to the Vanquish platform showed:

• Gradient delay volumes tunable to match various legacy systems (e.g., Waters Alliance, Agilent 1260)
• Improved chromatographic performance with reduced tailing factors and higher theoretical plates
• Lower limits of detection and enhanced signal-to-noise ratios
• Significant reduction in system suitability failures compared to legacy HPLC instruments

Qualification studies under different scenarios demonstrated that system suitability criteria and impurity results remained consistent within predefined acceptance thresholds.

Benefits and Practical Applications

The Vanquish UHPLC platform offers:

• Seamless method adaptation without extensive revalidation
• Backwards compatibility with legacy HPLC assays and modern UHPLC methods
• Enhanced robustness and serviceability in cGMP environments
• Streamlined regulatory compliance through well-documented method transfer protocols

Future Trends and Potential Applications

Emerging directions include:

• In-silico prediction of gradient delay adjustments using machine learning
• Automated AQbD tools for real-time method optimization
• Integration of modular LC components for rapid system reconfiguration
• Advanced data analytics to monitor long-term instrument performance

Conclusion

The transfer of HPLC methods to the Thermo Scientific Vanquish UHPLC platform simplifies modernization efforts, delivers superior chromatographic performance, and maintains regulatory compliance. Strategic GDV adjustment and instrument qualification protocols ensure a smooth transition and improved analytical outcomes.

References

1. Thermo Scientific Case Study 000565: Overcoming the challenges of liquid chromatography method transfer: A CDMO perspective.