Mitigation of chromatography adsorbent lot performance variability through control of buffer solution design space

Area of Science:

• Biochemistry
• Chemical Engineering
• Pharmaceutical Sciences

Background:

• Purifying protein therapeutics often involves challenging separations of product-related impurities like isoforms and aggregates.
• Anion exchange chromatography (AEC) is sensitive to operating conditions (pH, conductivity, temperature, loading) and adsorbent lot variability.
• Lot-to-lot variations in AEC adsorbents can impact separation performance and are difficult for manufacturers to control precisely.

Purpose of the Study:

• To develop a control strategy for AEC that accommodates adsorbent lot variability.
• To ensure consistent process performance and product quality in protein purification.
• To present a method for adjusting chromatography operating conditions based on adsorbent lot characteristics.

Main Methods:

• A design space-based control strategy using adjusted buffer solution composition was implemented for AEC.
• A "use test" was developed to determine optimal buffer compositions for different AEC adsorbent lots.
• The method relies on measuring the retention volume of the therapeutic protein during gradient elution.

Main Results:

• The proposed strategy effectively manages lot-to-lot variability in AEC performance.
• Consistent process performance and product quality were achieved through buffer composition adjustments.
• The "use test" provides a practical way to optimize conditions for specific adsorbent lots.

Conclusions:

• Adjusting buffer solution composition is a viable control strategy for AEC susceptible to adsorbent lot variability.
• This approach ensures reliable protein purification and consistent product quality.
• The described "use test" aids in optimizing AEC for diverse adsorbent lots.