Design of cell expansion processes for adherent-growing cells with mDoE-workflow

Area of Science:

• Biotechnology and Bioprocessing
• Cell Culture Technology
• Process Development

Background:

• Adherent mammalian cell cultures are crucial for producing viral vaccines, gene therapy vectors, and immuno-oncology agents.
• Scaling up adherent cell cultures presents challenges due to the need for increased surface area, with microcarrier (MC)-based systems being predominant.
• Developing MC processes is complex and time-consuming, necessitating innovative approaches for efficiency.

Purpose of the Study:

• To evaluate a model-assisted Design of Experiments (mDoE) workflow for optimizing MC-based adherent cell expansion.
• To reduce development time and costs in cell propagation processes.
• To demonstrate the successful application of mDoE with limited prior knowledge in early-stage process development.

Main Methods:

• Initial evaluation of analytical methods and screening of suitable microcarriers (MCs).
• Identification of cause-effect relationships between process parameters (e.g., medium conditions) and cell growth.
• Development and adaptation of a mathematical process model using experimental data.
• Application of the model in mDoE to identify optimized process conditions.

Main Results:

• Successful implementation of an mDoE workflow for MC-based L929 cell expansion.
• An eight-fold increase in cell yield was achieved through process optimization.
• Optimization was primarily driven by reducing the initial microcarrier concentration.

Conclusions:

• Model-assisted Design of Experiments (mDoE) is an effective strategy for accelerating the development of MC-based cell expansion processes.
• mDoE enables significant improvements in cell yield with reduced resources and time.
• Optimizing microcarrier concentration is a key factor in enhancing cell propagation efficiency.