A Comprehensive Assessment of All-Oleate Polysorbate 80: Free Fatty Acid Particle Formation, Interfacial Protection and Oxidative Degradation

Doshi, Nidhi; Giddings, Jamie; Luis, Lin; Wu, Arthur; Ritchie, Kyle; Liu, Wenqiang; Chan, Wayman; Taing, Rosalynn; Chu, Jeff; Sreedhara, Alavattam; Kannan, Aadithya; Kei, Pervina; Shieh, Ian C.; Graf, Tobias; Hu, Mark

doi:10.1007/s11095-021-03021-z

Cited by 32 publications

(28 citation statements)

References 63 publications

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“…Another recent study by Grabarek et al compared different grades of polysorbate 80 and found similar levels of performance when subjected to mechanical stress, such as shaking, free-fall, or syringe pump test ( 28 ). A recent study conducted to monitor hydrolytic degradation of polysorbates and formation of particles found homogenous all-oleate PS80 to be less prone to FFA particle formation compared to heterogenous PS80 ( 30 ). In alignment with these previous studies, we found that treatment of both types of polysorbate 80 used in this study with an esterase led to rapid hydrolysis as indicated by similar increases in FFA consistent with the composition of fatty acids in the two types of polysorbate we studied, and PS-80 HOA showed less susceptibility to particle formation compared to PS-80 NF (Fig.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fatty Acid Composition in Polysorbate 80 on the Stability of Therapeutic Protein Formulations

et al. 2021

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Purpose Polysorbate excipients are commonly used as surfactants to stabilize therapeutic proteins in formulations. Degradation of polysorbates could lead to particle formation and instability of the drug formulation. We investigated how the fatty acid composition of polysorbate 80 impacts the degradation profile, particle formation, and product stability under stress conditions. Methods Two polysorbate 80-containing therapeutic protein formulations were reformulated with either Polysorbate 80 NF synthesized from a fatty acid mixture that contains mainly oleic acid (≥58%) or a version of polysorbate 80 synthesized with high oleic acid (>98%). Stress conditions, including high temperature and esterase spiking, were applied and changes to both the polysorbate and the therapeutic protein product were investigated for stability, purity, innate immune response and biological activity. Results The addition of esterase and storage at 37°C led to significant hydrolysis of the polysorbate and increases in sub-visible particle formation for both polysorbates tested. The fatty acid composition of polysorbate 80 did not directly alter the stability profile of either therapeutic protein as measured by size exclusion chromatography, or significantly impact innate immune response or biological activity. However, formulations with Polysorbate 80 NF showed greater propensity for sub-visible particle formation under stress conditions. Conclusions These results suggest that composition of fatty acids in polysorbate 80 may be a promoter for sub-visible particulate formation under the stress conditions tested but may not impact protein aggregation or biological activity.

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Section: Discussionmentioning

confidence: 99%

Effect of Fatty Acid Composition in Polysorbate 80 on the Stability of Therapeutic Protein Formulations

et al. 2021

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“…9 In recent years, there have been reports on PS-related stability issues related to the use of polysorbates in biopharmaceutical products, mainly due to PS degradation induced particle formation by free fatty acids (FFA). [10][11][12][13][14][15][16][17] Due to these challenges and the importance of PS in pharmaceutical products, the scientific interest and focus on PS is steadily increasing, as evidenced by the rising number of biomedical literature referenced in PubMed (www.PubMed.gov) containing both polysorbate and protein as keywords in title or abstract of the publication (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Industry Perspective on the use and Characterization of Polysorbates for Biopharmaceutical Products Part 1: Survey Report on Current State and Common Practices for Handling and Control of Polysorbates

Wuchner

Chéry

et al. 2022

Journal of Pharmaceutical Sciences

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“…The sensitivity of different grades of PS-20 and PS-80 against enzymatic hydrolysis and oxidative degradation were compared [ 8 , 18 , 63 ]. No differences in the sensitivity toward enzymatic degradation were observed between MC and ChP grade PSs [ 8 , 18 ].…”

Section: Control Strategymentioning

confidence: 99%

“…No differences in the sensitivity toward enzymatic degradation were observed between MC and ChP grade PSs [ 8 , 18 ]. ChP grade PS-80 was reportedly to be less prone to FFA particle formation [ 63 ]. Thus, visible and subvisible particles were significantly delayed [ 63 ].…”

Section: Control Strategymentioning

confidence: 99%

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The measurement and control of high-risk host cell proteins for polysorbate degradation in biologics formulation

Wang

et al. 2022

Antibody Therapeutics

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Non-ionic surfactant polysorbates (PS), including PS-80 and PS-20, are commonly used in the formulation of biotherapeutic products for both preventing surface adsorption and acting as stabilizer against protein aggregation. Trace levels of residual host cell proteins (HCPs) with lipase or esterase enzymatic activity have been shown to degrade polysorbates in biologics formulation. The measurement and control of these low-abundance, high-risk HCPs for polysorbate degradation is an industry-wide challenge to achieve desired shelf-life of biopharmaceuticals in liquid formulation, especially for high-concentration formulation product development. Here, we reviewed the challenges, recent advances and future opportunities of analytical method development, risk assessment and control strategies for polysorbate degradation during formulation development with a focus on enzymatic degradation. Continued efforts to advance our understanding of polysorbate degradation in biologics formulation will help develop high-quality medicines for patients.

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A Comprehensive Assessment of All-Oleate Polysorbate 80: Free Fatty Acid Particle Formation, Interfacial Protection and Oxidative Degradation

Cited by 32 publications

References 63 publications

Effect of Fatty Acid Composition in Polysorbate 80 on the Stability of Therapeutic Protein Formulations

Effect of Fatty Acid Composition in Polysorbate 80 on the Stability of Therapeutic Protein Formulations

Industry Perspective on the use and Characterization of Polysorbates for Biopharmaceutical Products Part 1: Survey Report on Current State and Common Practices for Handling and Control of Polysorbates

The measurement and control of high-risk host cell proteins for polysorbate degradation in biologics formulation

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