Orthogonal pre-use and post-use efficiency testing for single-use anion exchange chromatography

Area of Science:

• Biopharmaceutical Manufacturing
• Chromatography
• Process Analytical Technology

Background:

• Single-use anion exchange (AEX) chromatography is crucial for biopharmaceutical purification.
• Ensuring device integrity and performance, particularly viral clearance, is paramount.
• Existing methods for verifying AEX device performance can be limited.

Purpose of the Study:

• To develop and validate efficiency tests for single-use AEX chromatography devices.
• To establish correlations between test outcomes and viral clearance performance.
• To provide assurance of device integrity and capacity prior to use in biopharmaceutical applications.

Main Methods:

• Development of three distinct efficiency tests for single-use AEX devices.
• Application of tests to six capsule formats under varying conditions (undamaged and damaged).
• Viral clearance assessment using Phi-X174 challenges in high-salt buffer.

Main Results:

• A pre-use pressure-based test identifies gross defects like seal breakage.
• Passing a post-use bubble point test correlates with ≥5 log reduction value (LRV) viral clearance.
• A novel pre-use AEX capacity test (chloride ion challenge) detects mechanical and chemical defects, correlating with >2 LRV viral clearance.

Conclusions:

• A combination of pre-use and post-use tests offers robust risk reduction for viral clearance in single-use AEX devices.
• These tests provide simple, reagent-efficient methods for ensuring device performance.
• The developed tests enhance the reliability of single-use AEX chromatography in biopharmaceutical purification.