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Research ArticleResearch

Quantification and Stability Impact Assessment of Drop Stresses in Biologic Drug Products

Mahsa Siavashpouri, Christina M. Bailey-Hytholt, Jean-Rene Authelin and Sanket Patke
PDA Journal of Pharmaceutical Science and Technology November 2022, 76 (6) 461-473; DOI: https://doi.org/10.5731/pdajpst.2021.012722
Mahsa Siavashpouri
1Biologics Drug Product Development, Sanofi, Framingham, MA; and
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Christina M. Bailey-Hytholt
1Biologics Drug Product Development, Sanofi, Framingham, MA; and
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Jean-Rene Authelin
2Biologics Drug Product Development, Sanofi, Vitry, France
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Sanket Patke
1Biologics Drug Product Development, Sanofi, Framingham, MA; and
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Abstract

Product can experience a combination of cavitation and agitation stresses as a result of dropping post-manufacture. We optimized terephthalic acid (TA) dosimetry, hydroxyphenyl fluorescein fluorimetry, and p-nitrophenol calorimetry as tools to detect and quantify the levels of hydroxyl radicals generated in solution. Using TA dosimetry, we determined the level of hydroxyl radicals generated from a vial drop and found that it is a function of drop height and fill volume and that protein and excipients may serve to mitigate but not completely quench the radicals. Additionally, we optimized sonication and friability as scale-down models to simulate dropping stresses and applied them to assess the impact on the stability of biologics. Our results suggest that chemical degradation dominates when a protein is subjected to cavitation stress alone, and that physical degradation induced by air–liquid and solid–liquid interfaces is the dominant degradation mode when there is a combination of cavitation and agitation stress. Taken together, this work provides a quick and simplistic approach that can be applied during drug product process development to evaluate the impact of drop stresses on the stability of biologic drug product.

  • Transportation stress
  • Drop stress
  • Cavitation
  • Friability
  • Interfacial stress
  • Scale-down models
  • © PDA, Inc. 2022
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PDA Journal of Pharmaceutical Science and Technology: 76 (6)
PDA Journal of Pharmaceutical Science and Technology
Vol. 76, Issue 6
November/December 2022
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Quantification and Stability Impact Assessment of Drop Stresses in Biologic Drug Products
Mahsa Siavashpouri, Christina M. Bailey-Hytholt, Jean-Rene Authelin, Sanket Patke
PDA Journal of Pharmaceutical Science and Technology Nov 2022, 76 (6) 461-473; DOI: 10.5731/pdajpst.2021.012722

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Quantification and Stability Impact Assessment of Drop Stresses in Biologic Drug Products
Mahsa Siavashpouri, Christina M. Bailey-Hytholt, Jean-Rene Authelin, Sanket Patke
PDA Journal of Pharmaceutical Science and Technology Nov 2022, 76 (6) 461-473; DOI: 10.5731/pdajpst.2021.012722
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Keywords

  • Transportation stress
  • Drop stress
  • Cavitation
  • Friability
  • Interfacial stress
  • Scale-down models

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