Current Technologies to Endotoxin Detection and Removal for Biopharmaceutical Purification
Endotoxins are the major contributors to the pyrogenic response caused by contaminated pharmaceutical products, formulation ingredients, and medical devices. Recombinant biopharmaceutical products are manufactured using living organisms, including Gram-negative bacteria. Upon the death of a Gram-negative bacterium, endotoxins (also known as lipopolysaccharides) in the outer cell membrane are released into the lysate where they 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 of methods to reduce and remove endotoxins by monitoring raw materials and in-process intermediates at critical steps, in addition to final drug product release testing. This review paper highlights a discussion on three major topics about endotoxin detection techniques, upstream processes for the production of therapeutic molecules, and downstream processes to eliminate endotoxins during product purification. Finally, we have evaluated the effectiveness of endotoxin removal processes from a perspective of high purity and low cost.
M. Schneier et al., "Current Technologies to Endotoxin Detection and Removal for Biopharmaceutical Purification," Biotechnology and Bioengineering, vol. 117, no. 8, pp. 2588 - 2609, Wiley, Aug 2020.
The definitive version is available at https://doi.org/10.1002/bit.27362
Chemical and Biochemical Engineering
Keywords and Phrases
Biopharmaceutical; Biosensors; Chromatography; Downstream Purification; Endotoxin; Endotoxin Detection; Endotoxin Removal; Gram-Negative Bacteria; Lipopolysaccharides; Protein Purification
International Standard Serial Number (ISSN)
Article - Journal
© 2020 Wiley, All rights reserved.
01 Aug 2020
This publication was developed under Assistance Agreement No. 83996201 awarded by the U.S. Environmental Protection Agency (EPA) and the Missouri Soybean Merchandising Council (MSMC) Project No. 20‐447‐21 (EPA) to SB.