Design of experiments applications in bioprocessing: Chromatography process development using split design of...

Area of Science:

• Biotechnology
• Chemical Engineering
• Process Development

Background:

• Chromatographic step development is a bottleneck in protein purification.
• Process performance depends on numerous interacting factors.
• Traditional design of experiments (DOE) can be resource-intensive due to many factors.

Purpose of the Study:

• To propose a split DOE approach for efficient chromatographic process development.
• To reduce the number of experiments required compared to traditional methods.
• To model multiple output responses using empirical equations and regression analysis.

Main Methods:

• Implemented a two-stage split DOE strategy based on process knowledge.
• The first DOE optimized high-impact factors with unknown effects.
• The second DOE fine-tuned known interacting factors; empirical modeling was used for response variables.

Main Results:

• Reduced experiments by 25% vs. central composite design and 72% vs. full factorial design.
• Demonstrated applicability through hydrophobic and cation exchange chromatography case studies.
• Empirical modeling effectively handled multiple output response variables.

Conclusions:

• The split DOE approach offers significant time and resource savings in process development.
• This methodology streamlines the optimization of chromatographic purification steps.
• It provides a practical solution for managing complex multi-factor experimental designs.