Alternatives to chromatographic separations

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Protein Purification

Background:

• Mammalian cell culture productivity was once a bottleneck in therapeutic monoclonal antibody (mAb) production.
• Advances in cell culture have increased mAb titers, shifting focus to downstream purification processes.
• Current chromatographic methods, while effective, face scalability challenges in high-throughput industrial manufacturing.

Purpose of the Study:

• To review and evaluate alternative purification strategies to traditional chromatography for large-scale mAb production.
• To identify methods that can enhance throughput and overcome limitations of column chromatography.
• To assess the potential of novel unit operations for industrial biopharmaceutical manufacturing.

Main Methods:

• Literature review and critical analysis of non-chromatographic purification techniques.
• Evaluation of precipitation, membrane chromatography, high-resolution ultrafiltration, crystallization, and high-pressure refolding.
• Assessment of scalability, throughput, and efficiency for industrial antibody production.

Main Results:

• Significant improvements in cell culture have made purification throughput a critical factor.
• Alternatives to chromatography show promise for increasing processing capacity.
• Techniques like precipitation and membrane chromatography offer potential advantages for large-scale operations.

Conclusions:

• The focus in industrial mAb production is shifting from upstream cell culture to downstream purification.
• Alternative purification methods are essential for meeting the demands of large-scale biopharmaceutical manufacturing.
• Evaluating these alternatives is crucial for optimizing throughput and overcoming current purification bottlenecks.