Copper impurity of iron raw material contributes to improved cell culture performance

Abstract

Cell culture medium (CCM) formulations are chemically defined to reduce lot‐to‐lot variability and complexity of the medium while still providing all essential nutrients supporting cell growth and productivity of various cell lines. However, raw material impurities may still introduce variations and inconsistencies to final CCM formulations. In one of our previous studies (Weiss et al. Biotechnol Prog. 2021;37(4):e3148), we have demonstrated the impact of iron raw material impurity on Chinese hamster ovary (CHO) cell performance and critical quality attributes (CQAs) of recombinant proteins within the Cellvento® 4CHO CCM platform by identifying manganese impurity as the main root cause for improved cell performance and altered glycosylation profiles. This study sought to investigate the impact of iron raw material impurities within another medium platform, namely EX‐CELL® Advanced CHO Fed‐Batch‐Medium. As opposed to previously published results, in this platform, copper instead of manganese impurity present within the used ferric ammonium citrate (FAC) iron source was responsible for an improved cell performance of a CHOZN® cell line and a slight difference in CQAs of the produced recombinant protein. The use of tightly controlled raw material specifications or the use of low impurity iron sources is therefore crucial to minimize the impact of impurities on cell performance in any CCM platform and thereby guarantee consistent and reproducible cell culture processes.

Exploring metabolic responses and pathway changes in CHO‐K1 cells under varied aeration conditions and copper supplementations using 1H NMR‐based metabolomics

“…[10,13] Copper is a cofactor for various enzymes engaged in mitochondrial and oxidative pathways, including the critical cytochrome c oxidase complex IV, which is pivotal to the electron transfer chain. [14] Additionally, heightened copper levels can elevate intracellular reactive oxygen species (ROS) levels, which, if unchecked, can engender oxidative damage and impact the CQAs of final products, particularly by augmenting the proportion of basic variants. [15,16] Consequently, the balance between copper's cellular requirement and its potential toxicity necessitates meticulous consideration.…”