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Current Technologies to Endotoxin Detection and Removal for Biopharmaceutical Purification
  • +2
  • Mason Schneier,
  • Sidharth Razdan,
  • Allison Miller,
  • Maria Briceno ,
  • Sutapa Barua
Mason Schneier
Missouri University of Science and Technology
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Sidharth Razdan
Missouri University of Science and Technology
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Allison Miller
Missouri University of Science and Technology
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Maria Briceno
Missouri University of Science and Technology
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Sutapa Barua
Missouri University of Science and Technology
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Peer review status:ACCEPTED

29 Nov 2019Submitted to Biotechnology and Bioengineering
02 Dec 2019Submission Checks Completed
02 Dec 2019Assigned to Editor
02 Dec 2019Reviewer(s) Assigned
24 Dec 2019Review(s) Completed, Editorial Evaluation Pending
24 Dec 2019Editorial Decision: Revise Major
21 Feb 20201st Revision Received
22 Feb 2020Assigned to Editor
22 Feb 2020Submission Checks Completed
07 Mar 2020Reviewer(s) Assigned
27 Mar 2020Review(s) Completed, Editorial Evaluation Pending
27 Mar 2020Editorial Decision: Revise Minor
21 Apr 20202nd Revision Received
21 Apr 2020Assigned to Editor
21 Apr 2020Submission Checks Completed
22 Apr 2020Review(s) Completed, Editorial Evaluation Pending
22 Apr 2020Editorial Decision: Accept

Abstract

Endotoxins are considered as the major contributors to the pyrogenic response observed with contaminated pharmaceutical products. Recombinant biopharmaceutical products are manufactured using living organisms, including gram-negative bacteria. Upon the death of a gram-negative bacteria, endotoxins (also known as lipopolysaccharides; LPS) in the outer cell membrane are released into the lysate where it can interact with and form bonds with biomolecules, including target therapeutic compounds. Endotoxin contamination of biologic products may also occur through water, raw materials such as excipients, media, additives, sera, equipment, containers closure systems, and expression systems used in manufacturing. The manufacturing process is therefore in critical need to reduce and remove endotoxins by monitoring raw materials and in-process intermediates at critical steps, in addition to final drug product release testing. In this review, a discussion regarding the progression of endotoxin detection techniques, from crude to refined are presented. We provide a brief overview of the upstream processed used to manufacture therapeutic products and then discuss various downstream purification techniques widely used to purify the products off endotoxins. Finally, we investigate the effectiveness of endotoxin purification processes, both from a perspective of precision as well as cost-effectiveness.