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ABSTRACT
Polysorbates (PSs) are a class of surfactants commonly used in the formulation of protein therapeutic agents to provide protection against denaturation and aggregation. When the PS in these drug formulations degrades, loss of stabilization of the protein therapeutic and formulation may occur, resulting in particulate formation or other undesirable changes in product critical quality attributes. Here, we present a simplified platform to predict long-term PS20 and PS80 degradation for monoclonal antibody drugs containing the PS-degrading enzyme lysosomal acid lipase. The platform was based on a temperature-dependent equation derived from existing PS20 degradation stability data. Accurate prediction of both PS20 and PS80 hydrolysis for as long as 2 years was achieved through short-term kinetics studies performed within 2 weeks. This platform substantially shortens the time required to determine the long-term stability of PS degradation and therefore can be used to guide the purification process and optimization of antibody formulations.
Abbreviations
| Name | = | Abbreviation |
| acetonitrile | = | ACN |
| Chinese hamster ovary | = | CHO |
| day at 37C | = | D37C |
| dithiothreitol | = | DTT |
| drug product | = | DP |
| drug substance | = | DS |
| free fatty acids | = | FFA |
| group XV lysosomal phospholipase A2 isomer X1 | = | LPLA2 |
| High Accuracy liquid particle counter | = | HIAC |
| host cell protein | = | HCP |
| iodoacetamide | = | IAM |
| isopropanol | = | IPA |
| lipoprotein lipase | = | LPL |
| liquid chromatography-charged aerosol detector | = | LC-CAD |
| lysosomal acid lipase | = | LAL |
| methanol | = | MeOH |
| Micro-Flow Imaging | = | MFI |
| monoclonal antibody | = | mAb |
| month at 5C | = | M5C |
| Multiple Reaction Monitoring | = | MRM |
| palmitoyl-protein thioesterase 1 | = | PPT1 |
| polysorbate | = | PS |
| polysorbate 20 | = | PS20 |
| polysorbate 80 | = | PS80 |
| polysorbate degrading enzyme | = | PSDE |
| relative humidity | = | RH |
| sialate O-acetylesterase | = | SIAE |
| sodium deoxycholate | = | SDC |
| sodium lauroyl sarcosinate | = | SLS |
| Trifluoroacetic acid | = | TFA |
Disclosure statement
No potential conflict of interest was reported by the author(s).
Supplemental material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19420862.2023.2232486