Modulation of mAb quality attributes using microliter scale fed-batch cultures.

Area of Science:

• Biotechnology and Bioprocessing
• Protein Engineering and Therapeutics

Background:

• Optimizing cell culture conditions is crucial for consistent monoclonal antibody (mAb) production.
• Understanding media and feed component impacts on mAb quality attributes is essential for robust manufacturing.

Purpose of the Study:

• To investigate the effects of media and feed components on mAb quality attributes using a high-throughput approach.
• To identify factors and their interactions that modulate critical quality attributes (CQAs) of mAbs.
• To assess the responsiveness of different CHO-S clonal cell lines to process variations.

Main Methods:

• A high-throughput, Design of Experiments (DoE) approach was employed in a 96-deepwell plate system.
• Six CHO-S clonal cell lines expressing the same mAb were cultured under 384 conditions (2 media x 6 components x 3 levels).
• Process performance (viable cell density, viability, titer) and product quality attributes (N-glycans, charge variants, aggregates, low molecular weight forms) were monitored.

Main Results:

• The screening identified key factors and combinations influencing mAb quality attributes.
• Significant differences in responsiveness to media and feed components were observed among clonal cell lines.
• The experimental design space effectively demonstrated the impact of tested factors on CQAs.

Conclusions:

• This high-throughput DoE approach provides valuable insights for modulating mAb quality attributes.
• The method effectively differentiates clonal cell line performance and quality attribute modulation potential.
• The integrated, resource-effective approach accelerates early-stage cell culture development and informs scale-up.