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Research ArticleResearch

Impact of Stainless Steel Exposure on the Oxidation of Polysorbate 80 in Histidine Placebo and Active Monoclonal Antibody Formulation

Ganapathy Gopalrathnam, Anant Navanithan Sharma, Steven Witt Dodd and Lihua Huang
PDA Journal of Pharmaceutical Science and Technology March 2018, 72 (2) 163-175; DOI: https://doi.org/10.5731/pdajpst.2017.008284
Ganapathy Gopalrathnam
1Bioproduct Pharma Design
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  • For correspondence: gopalrathnam_ganapathy@lilly.com
Anant Navanithan Sharma
1Bioproduct Pharma Design
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Steven Witt Dodd
1Bioproduct Pharma Design
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Lihua Huang
2Protein Characterization, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA
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Abstract

Rapid oxidation of polysorbate 80 in histidine buffer was observed upon brief exposure to stainless steel. Liquid chromatography–mass spectrometry analysis indicates degradation of both polyoxyethylene sorbitan and polyoxyethylene head groups and unsaturated fatty acid chains, with further confirmation by reversed-phase high-performance liquid chromatography data. Both Fe2+ and Fe3+ were shown to induce polysorbate 80 oxidation. The degree of oxidation in polysorbate 20 and polysorbate 80 are comparable for the head groups and saturated fatty acid esters. However, the same phenomenon was not observed with placebo or monoclonal antibody at a threshold protein concentration, formulated in sodium citrate, in combination with histidine and sodium citrate, or with Na2 ethylenediaminetetraacetic acid (EDTA). Further, polysorbate 80 oxidation was not observed with Lilly's antibody containing the active ingredient LY2951742, at or above a threshold concentration. Finally, no major polysorbate 80 degradation was observed in histidine buffer, with or without protein, in containers composed of glass or plastic, or when stainless steel exposure was otherwise completely absent. Finally, the 2-oxo oxidation form of histidine was not observed, but the other oxidation products and modifications of histidine were identified.

LAY ABSTRACT: Rapid oxidation of polysorbate 80 in histidine buffer was observed upon brief exposure to stainless steel. The degree of oxidation in polysorbate 80 and polysorbate 20 were comparable. However, the same phenomenon was not observed with placebo when formulated in sodium citrate, in combination with histidine and sodium citrate, or with Na2 ethylenediaminetetraacetic acid (EDTA). Polysorbate 80 oxidation was not observed with Lilly's antibody containing the active ingredient, LY2951742, at or above a threshold concentration. No major polysorbate 80 degradation in histidine buffer was observed when stainless steel contact was completely absent.

  • Polysorbate 80
  • Polysorbate 20
  • Histidine
  • Metal ion
  • Stainless steel
  • Oleic acid
  • Lauric acid
  • Citrate
  • Oxidation
  • Monoclonal antibody
  • © PDA, Inc. 2018
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PDA Journal of Pharmaceutical Science and Technology: 72 (2)
PDA Journal of Pharmaceutical Science and Technology
Vol. 72, Issue 2
March/April 2018
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Impact of Stainless Steel Exposure on the Oxidation of Polysorbate 80 in Histidine Placebo and Active Monoclonal Antibody Formulation
Ganapathy Gopalrathnam, Anant Navanithan Sharma, Steven Witt Dodd, Lihua Huang
PDA Journal of Pharmaceutical Science and Technology Mar 2018, 72 (2) 163-175; DOI: 10.5731/pdajpst.2017.008284
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Keywords

  • Polysorbate 80
  • Polysorbate 20
  • histidine
  • metal ion
  • stainless steel
  • Oleic acid
  • Lauric acid
  • Citrate
  • oxidation
  • monoclonal antibody

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Impact of Stainless Steel Exposure on the Oxidation of Polysorbate 80 in Histidine Placebo and Active Monoclonal Antibody Formulation
Ganapathy Gopalrathnam, Anant Navanithan Sharma, Steven Witt Dodd, Lihua Huang
PDA Journal of Pharmaceutical Science and Technology Mar 2018, 72 (2) 163-175; DOI: 10.5731/pdajpst.2017.008284

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