High throughput chromatography and analytics can inform viral clearance capabilities during downstream process...

Area of Science:

• Biotechnology
• Process Development
• Analytical Chemistry

Background:

• High throughput process development (HTPD) is crucial for optimizing biopharmaceutical manufacturing.
• Current HTPD methods face limitations in assessing viral clearance capabilities of chromatography resins.
• Efficient viral clearance is essential for ensuring the safety of biologic drugs.

Purpose of the Study:

• To adapt HTPD for assessing viral clearance using a model virus.
• To develop a sensitive assay for detecting the model virus in high-throughput experiments.
• To evaluate the viral clearance efficacy of different chromatography resins under various conditions.

Main Methods:

• Developed a BSL-1 compatible, non-infectious minute virus of mice (MVM) model (MVM-VLP) for viral clearance studies.
• Created an electrochemiluminescence immunoassay (ECLIA) for MVM-VLP detection with a 5-log dynamic range.
• Utilized HTPD with RoboColumns and liquid handling robotics to screen ion exchange chromatography resins for viral clearance.

Main Results:

• Successfully adapted HTPD for viral clearance assessment using MVM-VLP.
• The developed ECLIA assay demonstrated high sensitivity and dynamic range for MVM-VLP detection.
• Screening identified significant variability in viral clearance across different chromatography resins and operating conditions.

Conclusions:

• HTPD can be effectively employed for viral clearance assessment in process development.
• The developed MVM-VLP model and ECLIA assay provide a robust platform for screening chromatography resins.
• This approach has the potential to streamline process design and mitigate risks in viral clearance validation for biologics manufacturing.