Effects of process intensification on homogeneity of an IgG1:κ monoclonal antibody during perfusion culture

Liang, George; Madhavarao, Chikkathur N.; Morris, Caitlin; O’Connor, Thomas; Ashraf, Muhammad; Yoon, Seongkyu

doi:10.1007/s00253-024-13110-9

Title: Effects of process intensification on homogeneity of an IgG1:κ monoclonal antibody during perfusion culture

Journal Article · 26 March 2024 · Applied Microbiology and Biotechnology

DOI: https://doi.org/10.1007/s00253-024-13110-9 · OSTI ID:2471297

Liang, George ^[1];

^[2]; Morris, Caitlin ^[1]; O’Connor, Thomas ^[2]; Ashraf, Muhammad ^[2]; Yoon, Seongkyu ^[3]

U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States); Univ. of Massachusetts, Lowell, MA (United States)
U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States)
Univ. of Massachusetts, Lowell, MA (United States)

The pharmaceutical industry employs various strategies to improve cell productivity. These strategies include process intensification, culture media improvement, clonal selection, media supplementation and genetic engineering of cells. However, improved cell productivity has inherent risk of impacting product quality attributes (PQA). PQAs may affect the products’ efficacy via stability, bioavailability, or in vivo bioactivity. Variations in manufacturing process may introduce heterogeneity in the products by altering the type and extent of N-glycosylation, which is a PQA of therapeutic proteins. We investigated the effect of different cell densities representing increasing process intensification in a perfusion cell culture on the production of an IgG1-κ monoclonal antibody from a CHO-K1 cell line. This antibody is glycosylated both on light chain and heavy chain. Our results showed that the contents of glycosylation of IgG1-κ mAb increased in G0F and fucosylated type glycans as a group, whereas sialylated type glycans decreased, for the mAb whole protein. Overall, significant differences were observed in amounts of G0F, G1F, G0, G2FS1, and G2FS2 type glycans across all process intensification levels. G2FS2 and G2 type N-glycans were predominantly quantifiable from light chain rather than heavy chain. It may be concluded that there is a potential impact to product quality attributes of therapeutic proteins during process intensification via perfusion cell culture that needs to be assessed. Since during perfusion cell culture the product is collected throughout the duration of the process, lot allocation needs careful attention to process parameters, as PQAs are affected by the critical process parameters (CPPs).

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Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC); US Food and Drug Administration (FDA)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471297

Journal Information:: Applied Microbiology and Biotechnology, Journal Name: Applied Microbiology and Biotechnology Journal Issue: 1 Vol. 108; ISSN 0175-7598

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Effects of process intensification on homogeneity of an IgG1:κ monoclonal antibody during perfusion culture

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