Model-based process development for the purification of a modified human growth hormone using multimodal...

Area of Science:

• Biochemistry
• Chemical Engineering
• Biotechnology

Background:

• Downstream bioprocessing requires efficient purification of therapeutic proteins.
• Modified human growth hormone presents purification challenges, including aggregate removal.
• Multimodal chromatography offers versatile separation capabilities.

Purpose of the Study:

• To develop a highly selective purification process for modified human growth hormone using multimodal chromatography.
• To evaluate the effectiveness of calcium chloride and arginine hydrochloride as mobile phase modifiers.
• To demonstrate the utility of the steric mass action model for process description and verification.

Main Methods:

• Utilized multimodal Capto adhere resin for purification.
• Employed calcium chloride or arginine hydrochloride as mobile phase modifiers.
• Applied the steric mass action model and Latin hypercube sampling for analysis and optimization.

Main Results:

• Achieved highly selective purification of modified human growth hormone.
• Demonstrated significant clearance of product-related aggregates and host cell proteins.
• Validated the steric mass action model for accurately describing the chromatographic process and aggregate removal.

Conclusions:

• Multimodal chromatography with specific mobile phase modifiers is effective for modified human growth hormone purification.
• The steric mass action model aids in understanding and verifying the bioprocess.
• This study provides novel approaches for downstream bioprocessing and bioprocess verification.