Assessment of pyrogenic response of lipoteichoic acid by the monocyte activation test and the rabbit pyrogen test

Gimenes, Izabela; Caldeira, Cristiane; Presgrave, Octávio Augusto França; Moura, Wlamir Corrêa de; Bôas, Maria Helena Simões Villas

doi:10.1016/j.yrtph.2015.07.025

Cited by 14 publications

(1 citation statement)

References 17 publications

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“… 37 – 39 BET is simple and economical. However, BET can only detect bacterial endotoxins from gram-negative bacteria, 40 which is often interfered with when used to test solutions with a high protein content. 9 , 10 Horseshoe crabs have been protected by the state, leading to the suspended production of some Tachypleus amebocyte lysate reagents.…”

Section: Discussionmentioning

confidence: 99%

A novel alternative for pyrogen detection based on a transgenic cell line

He,

Yu,

et al. 2024

Sig Transduct Target Ther

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Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted ‘reduction, replacement and refinement’ principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.

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Section: Discussionmentioning

confidence: 99%

A novel alternative for pyrogen detection based on a transgenic cell line

He,

Yu,

et al. 2024

Sig Transduct Target Ther

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Current technologies to endotoxin detection and removal for biopharmaceutical purification

Schneier

Razdan

Miller

et al. 2020

Biotech & Bioengineering

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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.

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Understanding Endotoxin and β-Glucan Contamination in Nanotechnology-Based Drug Products

Neun

Dobrovolskaia

2019

Endotoxin Detection and Control in Pharma, Limulus, and Mammalian Systems

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Assessment of pyrogenic response of lipoteichoic acid by the monocyte activation test and the rabbit pyrogen test

Cited by 14 publications

References 17 publications

A novel alternative for pyrogen detection based on a transgenic cell line

A novel alternative for pyrogen detection based on a transgenic cell line

Current technologies to endotoxin detection and removal for biopharmaceutical purification

Understanding Endotoxin and β-Glucan Contamination in Nanotechnology-Based Drug Products

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