Sterile vs. Pyrogen-Free – These designations are important to understand. First of all, what is a pyrogen? Simply, a pyrogen is any substance that causes a fever. The most commonly thought of pyrogens are bacterial endotoxins and exotoxins, although the host body (human or animal) can also produce pyrogens. The most commonly assayed for pyrogen is lipopolysaccharide, or LPS. It is a component of the bacterial wall of Gram-negative bacteria and is released upon breakdown of the cell wall or bacterial cell lysis.
So, if something has been sterilized, it should be pyrogen-free, right? Wrong!
Sterility ensures the absence of viable living bacteria. However, the act of sterilizing a contaminated vial can actually result in the release and deposit of pyrogens, as sterilization destroys bacteria, leading to bacterial cell lysis and release of LPS or other endotoxins and exotoxins. Pyrogens are not destroyed by autoclaving, not filterable, and when injected intrathecally they are 1000 times more potent and dangerous. Pygrogen testing is done by the Limulus Amoebacyte Lysate test (LAL). This test involves the incubation of the sample to be tested with the lysate of amoebacytes of the horseshoe crab. Formation of an opaque gel following 60 minute incubation indicates presence of pyrogens. This test is simple, rapid, relatively inexpensive, very sensitive and can detect pyrogens on the ng/mL level.
Thus, it’s important to consider your specific needs in order to ensure that your needs are met by your product of choice.
- Sterile does not mean pyrogen-free.
- Manufacturing that takes into account pyrogen-free environments are best.
This is an excerpt from an article originally written by Dr. Cathie Miller, a former WHEATON Product Manager.