Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics: Structure and Degradation Pathways

Kerwin, Bruce A.

doi:10.1002/jps.21190

Cited by 641 publications

(477 citation statements)

References 80 publications

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“…45 Specifically, polysorbates undergo autooxidation that results in hydroperoxide formation, side-chain cleavage, and eventually formation of short chain acids such as formic acid, all of which having the potential to alter the stability of a biopharmaceutical product. 46 In addition, PS80 was previously found to contain significant concentrations of hydrogen peroxides with considerable lot-to-lot and manufacturer-to-manufacturer variabilities. 27 Awareness of and control against the effects of residual peroxides in surfactants are particularly important as these peroxides can potentially affect the chemical stability of oxidation-sensitive proteins, including mAbs, as previously shown.…”

Section: Discussionmentioning

confidence: 99%

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Morar-Mitrica

Puri

Sassi

et al. 2015

mAbs

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The physical and chemical integrity of a biopharmaceutical must be maintained not only during long-term storage but also during administration. Specifically for the intravenous (i.v.) delivery of a protein drug, loss of stability can occur when the protein formulation is compounded with i.v. bag diluents, thus modifying the original composition of the drug product. Here we present the challenges associated with the delivery of a low-dose, highly potent monoclonal antibody (mAb) via the i.v. route. Through parallel in-use stability studies and conventional formulation development, a drug product was developed in which adsorptive losses and critical oxidative degradation pathways were effectively controlled. This development approach enabled the i.v. administration of clinical doses in the range of 0.1 to 0.5 mg total protein, while ensuring liquid drug product storage stability under refrigerated conditions.

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Section: Discussionmentioning

confidence: 99%

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Morar-Mitrica

Puri

Sassi

et al. 2015

mAbs

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“…Error bars indicate the deviations of means obtained from four replicates using the li SPR system and two replicates using the Biacore T100. a hydrophobic tail (Kerwin, 2008) that suppresses nonspecific binding of proteins, by binding to the hydrophobic areas of the sensitive surface, thus displaying its hydrophilic head group to the samples.…”

Section: Spr Vs Biacore Sensitivitymentioning

confidence: 99%

Monitoring human serum albumin cell cultures using surface plasmon resonance (SPR) spectroscopy

Henseleit

Pohl

Bley

et al. 2015

J. Sens. Sens. Syst.

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Abstract. Continuously monitoring cell cultures is essential for both controlling critical parameters and improving understanding of key processes. An ideal technique in this context is surface plasmon resonance (SPR) spectroscopy, which essentially exploits changes in the angle of incident light that occur when molecules bind to a surface. It provides the ability to monitor real-time changes in small concentrations of various molecules, with no need for additional labels or sample preparation. Here we present an SPR-based immunoassay for monitoring concentrations of human serum albumin (HSA), and compare its sensitivity when used in conjunction with a Biacore platform and the cheaper, smaller li SPR system. In conjunction with either system, the immunoassay can detect HSA (a hepatocyte viability marker) at concentrations typically present in three-dimensional hepatocyte cultures mimicking the liver used to evaluate effects of drug candidates before exposure to humans or animals. Furthermore, in conjunction with the li SPR system, it is sufficiently sensitive to measure the much lower HSA levels present in skin-hepatocyte co-cultures.

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“…Autoxidation of ethylene oxide units is the dominant degradation process that occurs below 40°C, while hydrolysis of ester bonds becomes more important above this temperature (e.g., Kishore et al, 2011b, and references therein). Autoxidation produces peroxides, aldehydes, acids, ketones, n-alkanes, and fatty acid esters via radical initiation, propagation, and termination reactions (Kerwin, 2008;Kishore et al, 2011b). Autoxidation can be slowed by measures that prevent radical initiation, such as excluding peroxides, heat, light, and oxygen (Yao et al, 2009;Kishore et al, 2011a), or the addition of an antioxidant such as butylated hydroxytoluene (Donbrow, 1987), while removing transition metal ions such as copper can also reduce catalytic effects (Kerwin, 2008).…”

Section: Surfactants For Extraterrestrial Organic Extractionmentioning

confidence: 99%

“…Autoxidation produces peroxides, aldehydes, acids, ketones, n-alkanes, and fatty acid esters via radical initiation, propagation, and termination reactions (Kerwin, 2008;Kishore et al, 2011b). Autoxidation can be slowed by measures that prevent radical initiation, such as excluding peroxides, heat, light, and oxygen (Yao et al, 2009;Kishore et al, 2011a), or the addition of an antioxidant such as butylated hydroxytoluene (Donbrow, 1987), while removing transition metal ions such as copper can also reduce catalytic effects (Kerwin, 2008). Hydrolysis, which can be both acid-and base-catalyzed (Bates et al, 1973), produces fatty acids (Kerwin, 2008).…”

Section: Surfactants For Extraterrestrial Organic Extractionmentioning

confidence: 99%

Searching for Life on Mars: Degradation of Surfactant Solutions Used in Organic Extraction Experiments

et al. 2014

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Life-detection instruments on future Mars missions may use surfactant solutions to extract organic matter from samples of martian rocks. The thermal and radiation environments of space and Mars are capable of degrading these solutions, thereby reducing their ability to dissolve organic species. Successful extraction and detection of biosignatures on Mars requires an understanding of how degradation in extraterrestrial environments can affect surfactant performance. We exposed solutions of the surfactants polysorbate 80 (PS80), Zonyl FS-300, and poly[dimethylsiloxane-co-[3-(2-(2-hydroxyethoxy)ethoxy)propyl]methylsiloxane] (PDMSHEPMS) to elevated radiation and heat levels, combined with prolonged storage. Degradation was investigated by measuring changes in pH and electrical conductivity and by using the degraded solutions to extract a suite of organic compounds spiked onto grains of the martian soil simulant JSC Mars-1. Results indicate that the proton fluences expected during a mission to Mars do not cause significant degradation of surfactant compounds. Solutions of PS80 or PDMSHEPMS stored at -20°C are able to extract the spiked standards with acceptable recovery efficiencies. Extraction efficiencies for spiked standards decrease progressively with increasing temperature, and prolonged storage at 60°C renders the surfactant solutions ineffective. Neither the presence of ascorbic acid nor the choice of solvent unequivocally alters the efficiency of extraction of the spiked standards. Since degradation of polysorbates has the potential to produce organic compounds that could be mistaken for indigenous martian organic matter, the polysiloxane PDMSHEPMS may be a superior choice of surfactant for the exploration of Mars.

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Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics: Structure and Degradation Pathways

Cited by 641 publications

References 80 publications

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Monitoring human serum albumin cell cultures using surface plasmon resonance (SPR) spectroscopy

Searching for Life on Mars: Degradation of Surfactant Solutions Used in Organic Extraction Experiments

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