Dynamic optimization of an integrated cultivation-aggregation model for mAb production

Wil Jones, Dimitrios I. Gerogiorgis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Due to their proteinaceous structure, monoclonal antibodies (mAbs) are susceptible to irreversible aggregation, with harmful consequences on drug efficacy and patient safety. To mitigate this risk in modern biopharmaceutical processes, it is critical to comply with current good manufacturing practices (cGMP) and pursue operating strategies minimizing irreversible aggregation whilst also maximizing mAb throughput. These conflicting objectives are targeted in this study by formulating and analyzing an integrated dynamic model accounting for both cultivation and aggregation of mAbs from a Chinese Hamster Ovary (CHO) cell line. Two manipulated dynamic variables are considered here in simulation studies: firstly temperature manipulation within a batch reactor, and secondly feed flow manipulation within a series of isothermal fed-batch reactors. Following this, dynamic optimization investigations have been conducted, firstly with the single objective of maximizing mAb throughput and secondly with multiple (two) objectives of maximizing mAb throughput while also minimizing irreversible aggregate content, simultaneously. The study provides key insight into tradeoffs of how simultaneous temperature and feed flowrate manipulation affects mAb throughput and aggregation inside bioreactors.

Original languageEnglish
JournalBiotechnology and Bioengineering
Early online date1 Jun 2024
DOIs
Publication statusE-pub ahead of print - 1 Jun 2024

Keywords / Materials (for Non-textual outputs)

  • dynamic optimization
  • dynamic simulation
  • monoclonal antibodies (mAb)
  • protein aggregation

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