AI Article Synopsis
- Polysorbate degradation in biotherapeutics is a significant issue caused by enzymes from host cells, which can affect the stability of drug formulations.!* -
- A study demonstrated that by applying brief heat treatment, host cell-derived enzymes like PLA2G7 can be deactivated while minimizing damage to therapeutic monoclonal antibodies.!* -
- The findings propose that using heat to inactivate these enzymes can effectively slow down the degradation of polysorbate in biotherapeutic products.!*
Article 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.
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| http://dx.doi.org/10.1016/j.xphs.2023.10.038 | DOI Listing |
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