Heat Inactivation of Host Cell-Derived Enzymes as a Control Strategy for Polysorbate Degradation
JOURNAL OF PHARMACEUTICAL SCIENCES(2024)
Abstract
Polysorbate degradation in biotherapeutics formulations is an industry-wide problem and mainly caused by residual host cell-derived enzymes. We present a proof-of-concept study of a control strategy which takes advantage of lower thermal stability of such enzymes relative to therapeutic proteins. We profiled heat sensitivity of host cell-derived enzyme activity with chemical proteomics and observed that PLA2G7 became inactive after brief heating. Further biophysical studies indicated that these enzymes were less thermally stable than a monoclonal antibody. Importantly, brief heat treatment had minimal impact on the stability of the antibody. Consequently, heat inactivation of polysorbate-spiked protein-A pool decelerated polysorbate degradation. This study suggests that heat inactivation of host cell-derived enzymes could be a control stragy for polysorbate degradation. (c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
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Key words
Polysorbate,Lipase,mAb,Protein unfolding
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