Sterility and apyrogenicity
Additional safety issues related to radiopharmaceutical use in general include sterility and apyrogenicity of the drug product. Every product designed for parenteral use must be sterile and pyrogen-free. Sterility refers to absence of living things, including spores and related substances, that could develop into something living. Assessment of sterility is most commonly performed by culturing samples with special growth media.
Pyrogens are soluble compounds, typically bacterial endotoxins, which induce fevers in humans and other animals. They are not destroyed by autoclaving, are not filterable, and, when injected intrathecally, are estimated to be 1000 times as potent as when injected intravenously. While it is possible to depyrogenate solutions using sophisticated techniques, absence of pyrogens in reagents used to manufacture drug products is preferable.
Testing for pyrogens involves use of either the rabbit test or the Limulus Amoebacyte Lysate test (LAL). The rabbit test involves injection of the drug into three rabbits on a mg/kg basis so the animal dose approximates the human dose. Rectal temperatures are then taken at prescribed points in time post injection and the data recorded. Elevation of temperature indicates presence of pyrogenic material. This test is moderately sensitive for pyrogens.
The Limulus Amoebacyte Lysate test involves incubation of the sample to be tested with the lysate of amoebacytes of the horseshoe crab, limulus polyphemus. Formation of an opaque gel following 60 min incubation at 37oC indicates presence of pyrogens. This test is simple, rapid, relatively inexpensive, and very sensitive and can detect pyrogens on the ng/ml level.
|Stephen Karesh, PhD.||
Last Updated: August 14, 1996