Comprehensive manipulation of glycosylation profiles across development scales

Area of Science:

• Biopharmaceutical Manufacturing
• Glycobiology
• Protein Engineering

Background:

• Antibody glycosylation critically impacts therapeutic efficacy, pharmacokinetics, and immunogenicity.
• Controlling glycosylation is essential but challenging for biomanufacturing, especially for biosimilars undergoing process changes.
• Understanding glycan modulation is key for fine-tuning profiles but is often resource-intensive.

Purpose of the Study:

• To develop an inexpensive and adaptable screening system for comprehensive glycan modulation on antibodies.
• To map the design space for tuning glycosylation attributes using media additives and design of experiments.
• To establish a robust, scalable, and broadly applicable workflow for antibody glycan optimization.

Main Methods:

• Characterization of 10 media additives in univariable and combinatorial studies.
• Application of a design of experiments (DoE) approach to explore the glycan modulation space.
• Demonstration of scalability across various culture formats (deep wells to bioreactors) and host cell lineages.

Main Results:

• Identification of key media additives and combinations for glycan profile tuning.
• Establishment of a rapid, non-automated workflow for process optimization.
• Demonstration of the system's scalability and broad applicability to different antibodies and cell lines.

Conclusions:

• The developed screening system enables cost-effective and agile fine-tuning of antibody glycan product quality.
• This universal approach facilitates process optimization throughout the product lifecycle.
• The platform knowledge gained accelerates biopharmaceutical development and reduces costs.