A pyrogen is any substance that can cause a fever. Most pyrogens are endotoxins - usually lipopolysaccharide molecules from gram-negative bacteria.  These molecules are released on cell lysis, are toxic, cause fever and can trigger septic shock.
Endotoxins levels are measured in "endotoxins units" (EU). One EU is approximately equivalent to 100 pg of E. Coli lipopolysaccharide

The FDA limit for intrathecal injectable parenterals is 0.2 EU/kg of product. Vials or ampoules need to be substantially endotoxin-free before filling if this limit is to be attained. Sterilisation will not eliminate endotoxins. Two methods are in common use, both use dry heat. Depyrogenation tunnels are used for large scale continuous operation, batch ovens for smaller throughput.

Batch ovens use temperatures up to 250°C to deliver a sufficient reduction of endotoxin levels, typically taking 30 minutes exposure time. Make-up air entering the chamber is filtered to Grade A, internal polishing filters maintain this level from the start of the treatment phase until the end of cooling. Considerable care over detailed design is needed to ensure sufficient and uniform flow of heated air to all parts of the load.

The usual method for endotoxin detection is the Limulus Amoebocyte Lysate (LAL) test.  Extract from horseshoe crab blood is mixed with a sample and a reaction is observed if endotoxins are present.

 

Grade A Depyrogenation Ovens