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Brown drug substance color investigation in cell culture manufacturing using chemically defined media: A case study

Paper ID Volume ID Publish Year Pages File Format Full-Text
34834 45051 2014 10 PDF Available
Title
Brown drug substance color investigation in cell culture manufacturing using chemically defined media: A case study
Abstract

•Brown drug substance color was caused by iron and vitamin B12 in media.•Identified N-formylkynurenine and kynurenine associated with drug substance color.•The brown color was the result of mixing effect of yellow and pink colors.•Resolved the brown color issue in cell culture manufacturing.•Advanced knowledge on the mechanism of protein drug substance coloration.

Drug substance (DS) color is an important quality attribute for release, stability and comparability studies of biologics. With the increase of DS concentrations and biologics pipelines made in chemically defined media, atypical DS color other than colorless or pale yellow has been recently reported in the biopharmaceutical industry. We recently observed a brown DS color in manufacturing. Although analytical characterization data indicated that the brown color DS had no major quality issue, it is necessary to find the root cause and reduce DS color to ease placebo design for clinical use. It was demonstrated that the brown color was caused by the chemically defined basal medium containing high levels of iron and vitamin B12 (VB12) regardless of cell lines. Iron caused tryptophan oxidation in the protein to form N-formylkynurenine and kynurenine products, which likely contributed to a yellow DS color. A pink DS color was caused by the residual VB12 bound to DS. The brown color was the result of the combinatory effect of yellow and pink colors. Finally a modified basal medium was developed to produce a pale yellow DS in manufacturing.

Keywords
Protein drug substance color; N-formylkynurenine; Kynurenine; CHO cell culture; Chemically defined media; Iron
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Brown drug substance color investigation in cell culture manufacturing using chemically defined media: A case study
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 49, Issue 1, January 2014, Pages 130–139
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us