Advanced Pyrogen Testing

摘要

At the beginning of the 20th century the first commerciaily available infusion/injection solutions were administered to patients. Pyrogenic side effects termed "Injection fever" or "water fever" (associated to the diluent) were described occasionally. As a consequence the Rabbit Pyrogen Test (RPT) was implemented into the British pharmacopeia (1912), the United States Pharmacopeia followed in 1942. Since then both the predictive RPT and improved pharmaceutical manufacturing contributed to the safety level achieved today. Frequently the (nonspecific) RPT has been replaced by the (specific) Bacterial endotoxin test (BET). New in-vitro alternatives to the RPT as the Monocyte Activation Test (MAT) combine the advantages of the RPT (assessment of pyrogenicity beyond gram-negative endotoxin) with the benefits of an in-vitro method (non-animal, high-throughput, easy to modify). Several drugs (including modern vaccines containing detoxified endotoxin as adjuvant) will benefit from these new options. The replacement of animal experiments by validated alternatives is statutory according to European law.