Cell & Gene Therapy (CGT) products face a unique challenge in the required pyrogen testing for injectable wares. Since this test was written for conventional pharmaceuticals and medical devices, CGT products face special challenges in applying the endotoxin test to these goods.

Pyrogens are molecules that induce the human immune system to initiate a febrile response. Many of these are cytokines that are part of the immune system. These signalers are called endogenous pyrogens. However, molecules that originate from outside the body that initiate this pyrogen pathway are called exogenous pyrogens.

The most potent pyrogens are the lipopolysaccharide (LPS) molecule components of the outer membrane of gram-negative bacteria. It was known that drugs would frequently cause symptoms of septic shock even when sterilised. In 1942, the United States Pharmacopeia (USP) initiated USP <151> as the first pyrogen test requirement for parenteral and intrathecal injections.¹