Title

Comprehensive manipulation of glycosylation profiles across development scales

Conference Dates

May 6-11, 2018

Abstract

The extent and pattern of glycosylation can influence pharmacokinetics and effector functions of therapeutic monoclonal antibodies. Matching glycosylation product quality attributes within defined specification ranges when manufacturing a given antibody at different scales, different sites, or from different host cell lines poses a formidable challenge to the bio-manufacturing industry. One approach to control glycosylation attributes is to supplement cell culture media with additives known to influence glycosylation patterns. Here, we report a two-tier approach for the modulation of nine quality attributes in monoclonal antibodies expressed in CHO cells. In a first step, we tested ten different additives both in univariate and multivariate modes, pursuing a fractional factorial design-of-experiments approach in 24-well deep well format. We found several components to influence one or more quality attributes, either as single agents or in combination with other additives. As a second tier, we designed experiments to manipulate certain aspects of the glycosylation profile in a targeted fashion. We show proof of concept across different lab scale models, including deep wells, shake flasks, and 2L single-use bioreactors. Further, we characterized the extent of product quality modulation across CHO cell lines with different genetic background producing the same IgG1 molecule, and we characterized differences between a canonical IgG1 vs. an isotype-matched mAb with engineered cysteine residues. Taken together, this study provides comprehensive information about the extent and applicability of product quality modulation through media additives, and will enable the implementation of a robust process development platform.

Additional Files
123-Poster 71.pdf (84 kB)

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