In order to produce pyrogen-free pharmaceuticals, it is mandatory to use only sterile, pyrogen-free reagents, solvents, disposables and equipment.

In addition, only containers known to be pyrogen-free may be used for drug storage. Equipment and disposables should be handled only with sterile gloves and all work should be performed in a laminar flow hood equipped with a HEPA (High Efficiency Particulate Attenuation) filter. This filter traps all particulates~ 3 !Lm in diameter. Since pathogens are typically larger than this limit, sterile, particulate-free air is produced. Direction of flow of this sterile air prevents product contamination by room air. Often it is necessary to depyrogenate glassware and other heat-stable equipment. This is accomplished by dry heat for 2 hr at 19o•c.

Glass vials and bottles of all sizes are routinely depyrogenated by pharmaceutical manufacturers prior to filling them with their final product in order to eliminate a potential source of pyrogenic reactions. For solutions with low-level pyrogen contamination, affinity chromatography techniques are available (26,27), which effectively remove significant quantities of pyrogens. In addition, commercially available filters* are capable of removing pyrogens by an adsorption process (28,29). While these procedures do not completely eliminate soluble pyrogens, the level of pyrogens may be reduced sufficiently to pass the LAL or USP Rabbit Test for pyrogens.