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The important test for pyrogens in biologics as a measure of purity and integrity of the biological product was elevated technologically in research the FDA Bureau of Biologics pursued in 1980. For products derived from bacteria, pyrogens can be found in either the cell wall of the bacteria (an “endotoxin”) or from within the cell (an “endogenous toxin”).  Emergence of the so-called “Limulus amoebocyte lysate” (LAL) test changed the sensitivity of pyrogenic analysis. Traditionally, the material to be tested was injected into a rabbit to check for the presence of an endotoxin. However, pyrogens are not always pyrogenic for both humans and rabbits.  In the LAS test procedure, if a pyrogen is present it will produce a temperature when the test substance is treated and then administered to the rabbit. The LAL test, with radioimmunoassay, can also be used for endogenous pyrogens.

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A line of rabbits with only their heads accessible through a lab bench as two scientists administer something to a rabbit as they conduct an experiment

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Rabbits being used in testing at DBS in 1960s

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1968 publication "The Division of Biologics Standards" (Public Health Service Publication No. 1744) by Dr. Roderick Murray

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Professional photograph of a man with glasses in a suit.

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Dr. Edward B. Seligmann

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The NIH Record April 30, 1968

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A horseshoe crab on the beach

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Horseshoe Crab

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Alan Levine flickr.com/photos/cogdog/6224395337