z-logo
Premium
Scale‐dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies
Author(s) -
Williamson Jenna,
Miller Jennifer,
McLaughlin Joseph,
Combs Rodney,
Chu Chia
Publication year - 2018
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.2662
Subject(s) - leaching (pedology) , glycosylation , monoclonal antibody , chemistry , antibody , bioreactor , biochemistry , biology , immunology , organic chemistry , ecology , soil water
N ‐linked glycosylation profiles are routinely characterized on mammalian‐derived protein therapeutic products and achieving consistency in the product‐associated glycan attributes is an important indicator that the manufacturing process is under control. More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy. During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2‐L, 100‐L, and 6,000‐L scales were observed. Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time. Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike‐in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles. Surprisingly, the 2‐L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation. The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors. The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control. © 2018 American Institute of Chemical Engineers Biotechnol. Prog. , 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog. , 34:1290–1297, 2018

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here