A simultaneous assessment metric for MAb quantity and glycan quality

Abstract

As a critical quality attribute, glycosylation represents an important consideration when analyzing the success of a glycoprotein production process. Though critical, glycosylation is not the only measure of culture success; other factors, including culture size, maintenance, and productivity, are also critical. A new metric was developed to address both product quality, as measured through glycosylation, and product quantity, as measured through product concentration. A monoclonal antibody Chinese hamster ovary cell culture model system was used to assess this metric across various media formulations. In a model test system, the metric discriminated that some media supplements had a net positive impact on productivity and glycosylation, while others had a net negative impact on productivity and glycosylation.

Keywords: Chinese hamster ovary cells (CHO); Critical quality attributes; Glycosylation; Monoclonal antibodies; Productivity.

Fig. 1

There is an inverse relationship between the final protein titer [P] (grey bars) and the glycan quality QI (black bars) (left). Titer Quality, as a measure of both product quality and product quantity, is useful when evaluating net culture performance (right). BIOGRO CHO outperformed all other treatments in terms of TQ, while M6 exhibited a TQ approaching that of BIOGRO CHO. This differs from a focus strictly on productivity, where the final protein concentration in BIOGRO CHO is nearly double that of the next best formulation (mixture #6)

Fig. 2

Chromatograms for the glycan analysis of M3, M6 and BIOGRO CHO. Percentage of each glycan in a sample is measured as the relative percentage of the area under each peak. Identification of the species is conducted using a dextran ladder

Fig. 3

M6, containing high levels of HYPEP™1510 and SITE but low levels of UMG and LM1, exhibited a nearly twofold increase in the maintenance of population viability over the positive control BIOGRO CHO