This document discusses pyrogens, which are fever-producing substances produced by microorganisms. Pyrogens are lipid substances associated with a carrier molecule like a polysaccharide or peptide. They are classified as either endogenous or exogenous pyrogens. Endogenous pyrogens are proteins produced by leukocytes that induce fever by acting on the hypothalamus, while exogenous pyrogens come from external sources like bacterial endotoxins. Potential sources of pyrogens include water used in drug purification, crystallization, or packaging processes as well as chemicals or equipment used in product preparation.

1. PYREXIA OF
UNKNOWN ORIGIN
P Y R OG EN S

2. Pyrogens
• PYROGENS
• ▸ Pyrogens are fever producing substances, which are metabolic products of
microorganisms.
• Chemically, they are lipid substances associated with a carrier molecule, which is usually a
polysaccharide. The carrier may also be a peptide. These carriers increase the solubility of the
lipid.
• ▸ Pyrogens are produced by many microorganisms including bacteria, yeasts and moulds.
Most potent pyrogens are the endotoxins produced from the cell walls of the Gram-negative
bacteria.

3. Classification of pyrogens
• Classification of Pyrogens
• ▸ Exogenous Pyrogen (Exotoxins)
• > Endogenous Pyrogen (Endotoxin)

4. Classification of pyrogens
• 1.Endogenous pyrogen
• low-molecular-weight protein is produced by phagocytic leukocytes in response to
stimulation by exogenous pyrogens and released into the circulation.
• It induces fever by acting on the preoptic area of the hypothalamus to raise the set-point
of the hypothalamic thermostat..

5. Classification of pyrogens
• 2.Exogenous pyrogen
• fever-producing agents of external origin,
• e.g., bacterial endotoxins and other microbial products, antigen-antibodycomplexes,
viruses and synthetic polynucleotides, incompatible blood and blood products, and
androgen breakdown products such as etiocholanolone.

6. Source of pyrogens
• Source of pyrogen
• water used at the end stages of the purification.
• ⚫ crystallization of the drug or excipients: water used during
• processing.
• ⚫ packaging components; chemicals, raw materials or equipment used in the preparation of the product.
• • The presence of endotoxins on devices may be attributed to water in the manufacturing process.
• Washing of components such as filter media (filters). Washing/rinsing of tubing or other plastic devices
prior to their sterilization.