Enhancing Protein A performance in mAb processing: A method to reduce and rapidly evaluate host cell DNA levels...

Area of Science:

• Biotechnology
• Bioprocessing
• Chromatography

Background:

• Host cell DNA (HC-DNA) is a critical impurity in monoclonal antibody (mAb) production.
• Effective primary clarification is essential for downstream purification efficiency.
• Traditional depth filtration may not sufficiently reduce HC-DNA and can impact subsequent chromatography steps.

Purpose of the Study:

• To evaluate the efficacy of 3M™ Emphaze™ AEX Hybrid Purifier for HC-DNA reduction during mAb primary clarification.
• To assess the impact of Emphaze AEX Hybrid Purifier on Protein A chromatography performance.
• To investigate a rapid acidification assay for HC-DNA monitoring.

Main Methods:

• Utilized 3M™ Emphaze™ AEX Hybrid Purifier, a single-use synthetic chromatographic product, for primary clarification.
• Compared performance against traditional depth filtration.
• Employed turbidimetric and particle size measurements for an acidification-induced HC-DNA precipitation assay.

Main Results:

• Achieved an approximate 5-log reduction in HC-DNA at a throughput of 200 L/m².
• Observed enhanced Protein A chromatography with a sharper, narrower elution profile.
• Demonstrated a 24× improvement in host cell protein (HCP) removal and reduced non-specific binding compared to depth filtration.

Conclusions:

• Emphaze™ AEX Hybrid Purifier effectively reduces HC-DNA during primary clarification, improving downstream processing.
• The synthetic purifier enhances Protein A chromatography performance and impurity removal.
• A rapid acidification assay is suitable for monitoring HC-DNA breakthrough during purification.