Development of a serum free medium for HUMIRA® biosimilar by design of experiment approaches

Abstract

Background: Serum have been traditionally used to support growth of animal cell cultures. However, the increasing growth of therapeutic biopharmaceuticals market, accelerated the high demand for the serum-free medium (SFM). Objective: The main objective is to design a SFM for a stable rCHO cell line that produces a fully anti-human TNF-α monoclonal antibody (mAb) corresponding to HUMIRA® biosimilar. Materials and methods: Design of Experiment (DoE) approaches were used to determine the key factors due to their effect on specific growth rate and mAb production. The production was carried out in T-flasks at different initial cell concentrations and then in Erlenmeyers with the developed SFM. mAb production was compared with commercial SFMs in terms of yield and productivity. Results: Regarding to our findings, when the developed SFM-adapted cells were compared with the cells produced in commercial SFMs, the mAb productivity in developed SFM were higher (1.3-1.6 times) depending on higher mAb concentration and less (3-5 times) cell concentration. Additionally, the produced mAb in the developed SFM provided high conformational similarity with its originator HUMIRA®. Conclusion: DoE approaches could be used to reduce cost and time in designing SFM for any commercially important cell line to produce high value biologics.