New approaches to the issue of pyrogens in parenteral preparations

Abstract

New approaches to the issue of pyrogens in parenteral preparations The article provides a basic understanding of the pathophysiology of exogenous and endogenous pyrogens, particularly in the context of parenteral administration of drugs and the use of medical devices. It explains that pyrogens cause an increase in body temperature by activating the thermoregulatory center in the hypothalamus, with bacterial lipopolysaccharides being the most common source of pyrogenic burden. Contamination of pharmaceuticals with pyrogenic substances can lead to adverse effects, including life-threatening conditions. The text focuses on modern methods for identifying pyrogens, specifically endotoxins, and selecting suitable analytical procedures for their determination. These include in vivo tests on rabbits and the bacterial endotoxin tests, as well as in vitro tests such as the monocyte activation test and the recombinant Factor C test. The work includes a detailed description how to perform these tests, their advantages and disadvantages, and the development of methods for detecting pyrogens in pharmaceuticals. The author explains the reasons of false positive and negative test results, and ilusrates the calculations of threshold endotoxin limits. Information is provided on the new strategy of the European and Czech Pharmacopoeias on this issue, emphasizing efforts to reduce pyrogenic burden and the need to control both microbiological and endotoxin contamination levels.

Keywords: Endotoxins; limits.; pyrogens; testing.