Large-scale crystallization as an intermediate processing step in insulin downstream process: explored advantages and...

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Process Intensification

Background:

• Global diabetes prevalence necessitates increased insulin accessibility and affordability.
• Downstream processing is a common bottleneck in high-volume biopharmaceutical manufacturing.
• Process integration and intensification are key to improving efficiency and reducing production costs.

Purpose of the Study:

• To explore the pH-dependent zinc-insulin complex formation for improved manufacturing.
• To evaluate zinc chloride precipitation/crystallization as a cost-effective purification method.
• To demonstrate the potential of this method in replacing expensive capture chromatography steps.

Main Methods:

• Investigated the properties of insulin in forming pH-dependent zinc-insulin complexes.
• Utilized zinc chloride precipitation/crystallization as a unit operation.
• Assessed the impact on product purity and reduction of impurities.
• Evaluated changes in process volume, buffer consumption, and equipment footprint.

Main Results:

• Zinc chloride precipitation/crystallization significantly increased in-process product purity.
• Reduced product and process-related impurities were observed.
• The method showed potential to replace high-cost capture chromatography.
• Demonstrated reduction in operational volume, buffer use, and equipment footprint.

Conclusions:

• Zinc chloride precipitation is an efficient and cost-effective unit operation for insulin purification.
• This method offers significant manufacturing flexibility and cost savings.
• The findings support broader adoption for insulin and biosimilar manufacturers seeking cost-effective production.