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Review
. 2018 Aug 16;10(8):331.
doi: 10.3390/toxins10080331.

Endotoxins from a Pharmacopoeial Point of View

Elvira Franco  1   2 , Verónica Garcia-Recio  3 , Pilar Jiménez  4 , Manuel Garrosa  5 , Tomás Girbés  6 , Manuel Cordoba-Diaz  7   8 , Damián Cordoba-Diaz  9   10
Affiliations
Review

Endotoxins from a Pharmacopoeial Point of View

Elvira Franco et al. Toxins (Basel). .

Abstract

A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicitythat is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.

Keywords: endotoxins; harmonization; parenteral drug products; pharmacopoeial test; pyrogens.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Most significant pyrogens for pharmaceutical manufacturers and sequential events of fever. GNB = Gram-negative bacteria.
See this image and copyright information in PMC

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