Abstract:
:While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to the higher molecular density across a given path-length. Color is therefore a product quality attribute that must be well-understood and controlled, to demonstrate process consistency and enable clinical trial blinding. Upon concentration of an IgG4 product at the 2000 L manufacturing scale, variability in product color, ranging from yellow to red, was observed. A small-scale experimental model was developed to assess the effect of processing conditions (medium composition and harvest conditions) on final bulk drug substance (BDS) color. The model was used to demonstrate that, for two distinct IgG4 products, red coloration occurred only in the presence of disulfide reduction-mediated antibody dissociation. The red color-causing component was identified as vitamin B 12, in the hydroxocobalamin form, and the extent of red color was correlated with the cobalt (vitamin B 12) concentration in the final pools. The intensity of redness in the final BDS was modulated by changing the concentration of vitamin B 12 in the cell culture media.
journal_name
MAbsjournal_title
mAbsauthors
Derfus GE,Dizon-Maspat J,Broddrick JT,Velayo AC,Toschi JD,Santuray RT,Hsu SK,Winter CM,Krishnan R,Amanullah Adoi
10.4161/mabs.28257subject
Has Abstractpub_date
2014-05-01 00:00:00pages
679-88issue
3eissn
1942-0862issn
1942-0870pii
28257journal_volume
6pub_type
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