Work

Hybrid Modeling of CHO Cell Cultivation in Monoclonal Antibody Production with an Impurity Generation Module

Year: 2022

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Representative cultivation models are needed for designing efficient monoclonal antibody (mAb) production processes. Simple Monod-type kinetic models could fail to capture changes at different phases and conditions. Current models rarely account for process-related impurities, which hinders optimizing integrated processes. A three-module hybrid approach is thus introduced here. Module 1 is a kinetic metabolism model until cell death based on Monod-type equations. Module 2 is a data-driven module for updating parameters based on system dynamics and changes in cultivation conditions. Module 3 proposes a kinetic model for the generation of host cell proteins and DNA. The model is applied to newly established high-performance CHO cell lines and is validated with experiments at different operating conditions. The adopted modular approach helps identify weak model links, which can be corrected via the data-driven module. The proposed model combines accuracy and simplicity for design and control applications of cultivation processes considering quality aspects.

Source: Industrial & Engineering Chemistry Research

DOI: 10.1021/acs.iecr.2c00736

Authors: Kozue Okamura, Sara Badr, Sei Murakami, Hirokazu Sugiyama

Institutions: The University of Tokyo, Manufacturing Technology Association of Biologics

Language: English

Topic: Viral Infectious Diseases and Gene Expression in Insects

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $5,000

Funder: Japan Agency for Medical Research and Development